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Sample records for efficient stereoselective synthesis

  1. A concise and stereoselective synthesis of squalamine.

    PubMed

    Zhang, Dong-Hui; Cai, Feng; Zhou, Xiang-Dong; Zhou, Wei-Shan

    2003-09-01

    [reaction: see text] A short and highly stereoselective synthesis of the novel steroid squalamine (1) was accomplished in nine steps from easily available methyl chenodeoxylcholanate 2. Our synthesis featured improved dehydrogenation of 4 followed by conjugate reduction to construct the trans AB-ring system and efficient asymmetric isopropylation of aldehyde 6 to introduce the C-24R-hydroxyl group. PMID:12943401

  2. Stereoselectivity in N-Iminium Ion Cyclization: Development of an Efficient Synthesis of (±)-Cephalotaxine.

    PubMed

    Liu, Hao; Yu, Jing; Li, Xinyu; Yan, Rui; Xiao, Ji-Chang; Hong, Ran

    2015-09-18

    A stereoselective N-iminium ion cyclization with allylsilane to construct vicinal quaternary-tertiary carbon centers was developed for the concise synthesis of (±)-cephalotaxine. The current strategy features a TiCl4-promoted cyclization and ring-closure metathesis to furnish the spiro-ring system. The stereochemical outcome in the N-acyliminium ion cyclization was rationalized by the stereoelectronic effect of the Z- or E-allylsilane. Two diastereomers arising from the cyclization were merged into the formal synthesis of (±)-cephalotaxine. PMID:26332648

  3. Novel and efficient one-pot five- and six-component reactions for the stereoselective synthesis of highly functionalized enaminones and dithiocarbamates.

    PubMed

    Bararjanian, Morteza; Balalaie, Saeed; Rominger, Frank; Movassagh, Barahman; Bijanzadeh, Hamid Reza

    2011-05-01

    Efficient methods for stereoselective synthesis of polyfunctional (E)-enaminones and (Z)-dithiocarbamates via one-pot five- and six-component sequential Ugi/Nucleophilic addition reactions are described. High yields and high bond forming efficiency, and simple operations are the advantages of this method. PMID:21072590

  4. Organoselenium-catalyzed, hydroxy-controlled regio- and stereoselective amination of terminal alkenes: efficient synthesis of 3-amino allylic alcohols.

    PubMed

    Deng, Zhimin; Wei, Jialiang; Liao, Lihao; Huang, Haiyan; Zhao, Xiaodan

    2015-04-17

    An efficient route to prepare 3-amino allylic alcohols in excellent regio- and stereoselectivity in the presence of bases by orangoselenium catalysis has been developed. In the absence of bases α,β-unsaturated aldehydes were formed in up to 97% yield. Control experiments reveal that the hydroxy group is crucial for the direct amination. PMID:25849818

  5. Stereoselective Synthesis of Alkylidene Phthalides.

    PubMed

    Dragan, Andrei; Jones, D Heulyn; Kennedy, Alan R; Tomkinson, Nicholas C O

    2016-07-01

    The N,O-diacylhydroxylamine derivative 4 has been prepared and its reactivity with nucleophiles investigated. On reaction with lithium enolates of cyclic or acyclic ketones, 4 is converted stereoselectively to the corresponding alkylidene phthalide. The stereochemical outcome of the transformation can be modified by changing the polarity of the reaction medium and the products isomerized under acidic conditions. PMID:27311815

  6. Stereoselective synthesis and antitumoral activity of Z-enyne pseudoglycosides.

    PubMed

    Dantas, Claudio R; de Freitas, Jucleiton J R; Barbosa, Queila P S; Militão, Gardenia C G; Silva, Thiago D S; da Silva, Teresinha G; Paulino, Antônio A S; Freitas, Juliano C R; Oliveira, Roberta A; Menezes, Paulo H

    2016-07-12

    An efficient approach for the synthesis of Z-1,3-enynes based on the coupling reaction of Z-vinyl tellurides and alkynes containing a pseudoglycoside moiety is described. The products were obtained in good yields via a stereoselective way. Preliminary screening against three tumor cell lines indicated that the synthesized compounds are promising intermediates for the synthesis of an array of more potent target structures. PMID:27336326

  7. Stereoselective Synthesis of Conjugated Fluoro Enynes

    PubMed Central

    Kumar, Rakesh; Zajc, Barbara

    2013-01-01

    Metalation-electrophilic fluorination of TMS- and TIPS-protected 1,3-benzothiazol-2-yl (BT) propargyl sulfones gave corresponding BT fluoropropargyl sulfones, Julia-Kocienski reagents for the synthesis of fluoro enynes. Both reagents reacted with aldehydes under mild DBU, or LHMDS-mediated conditions, giving high yields of conjugated fluoro enynes with E- stereoselectivity. In comparison to DBU-mediated reactions, stereoselectivity was higher in low-temperature LHMDS-mediated reactions. Two ketones were shown to react as well, using LHMDS as base. In situ removal of the TMS group gave terminal conjugated 2-fluoro 1,3-enynes. Synthetic utility of the fluoro enynes was demonstrated by conversion to internal alkynes and to stereoisomeric fluoro dienes via Sonogashira and Heck couplings. PMID:23005035

  8. Stereoselective Synthesis of the C9-C19 Fragment of Lyngbyaloside B and C via Ether Transfer

    PubMed Central

    Stefan, Eric; Taylor, Richard E.

    2012-01-01

    A stereoselective synthesis of the C9-C19 fragment of lyngbyaloside B and C highlighted, by an extension of our ether transfer methodology, enables the formation of tertiary ethers. 2-Naphthylmethyl ethers have been shown to proceed efficiently through ether transfer with high stereoselectivity and are easily deprotected by DDQ oxidation. Variation of the workup conditions results in the stereoselective formation of syn-1,3-diol mono- or diethers. PMID:22716968

  9. Catalytic Stereoselective Synthesis of Diverse Oxindoles and Spirooxindoles from Isatins

    PubMed Central

    MacDonald, Jacob P.; Badillo, Joseph J.; Arevalo, Gary E.; Silva-Garcia, Abel

    2015-01-01

    A strategy for the efficient two-step synthesis of triazole derivatives of oxindoles and spirooxindoles is presented. Using a common set of N-propargylated isatins, a series of mechanistically-distinct stereoselective reactions with different combinations of nucleophiles and catalysts provide access to diverse hydroxy-oxindoles, spiroindolones, and spirocyclic oxazoline structures. The resulting N-propargylated oxindoles are then converted to triazoles using copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Overall, this strategy affords a 64-member pilot-scale library of diverse oxindoles and spirooxindoles. PMID:22449252

  10. Regioselective and stereoselective cyclizations of chloropolyols in water: rapid synthesis of hydroxytetrahydrofurans.

    PubMed

    Kang, Baldip; Chang, Stanley; Decker, Shannon; Britton, Robert

    2010-04-16

    A concise, stereoselective synthesis of functionalized tetrahydrofuranols has been developed that involves heating readily available chloropolyols in water. These reactions are operationally straightforward and chemoselective for the formation of tetrahydrofurans, obviating the need for complicated protecting group strategies. The efficiency of this process is demonstrated in a short asymmetric synthesis of the natural product (+)-goniothalesdiol. PMID:20297827

  11. Witting Reaction Using a Stabilized Phosphorus Ylid: An Efficient and Stereoselective Synthesis of Ethyl Trans-Cinnamate

    ERIC Educational Resources Information Center

    Speed, Traci J.; Mclntyre, Jean P.; Thamattoor, Dasan M.

    2004-01-01

    An instructive experiment for the synthesis of ethyl trans-cinnamate, a pleasant smelling ester used in perfumery and flavoring by the reaction of benzaldehyde with the stable ylid triphenylphosphorane is described. The synthesis, workup and characterization of trans-cinnamate may be accomplished in a single laboratory session with commonly…

  12. Highly Stereoselective Synthesis of Cyclopentanes bearing Four Stereocenters by a Rhodium Carbene–Initiated Domino Sequence

    PubMed Central

    Parr, Brendan T.; Davies, Huw M. L.

    2014-01-01

    Stereoselective synthesis of a cyclopentane nucleus by convergent annulations constitutes a significant challenge for synthetic chemists. Though a number of biologically relevant cyclopentane natural products are known, more often than not, the cyclopentane core is assembled in a stepwise fashion due to lack of efficient annulation strategies. Herein, we report the rhodium-catalyzed reactions of vinyldiazoacetates with (E)-1,3-disubstituted 2-butenols generate cyclopentanes, containing four new stereogenic centers with very high levels of stereoselectivity (99% ee, >97 : 3 dr). The reaction proceeds by a carbene–initiated domino sequence consisting of five distinct steps: rhodium–bound oxonium ylide formation, [2,3]-sigmatropic rearrangement, oxy-Cope rearrangement, enol–keto tautomerization, and finally an intramolecular carbonyl ene reaction. A systematic study is presented detailing how to control chirality transfer in each of the four stereo-defining steps of the cascade, consummating in the development of a highly stereoselective process. PMID:25082301

  13. Recent advances in stereoselective synthesis of 1,3-dienes.

    PubMed

    De Paolis, Michael; Chataigner, Isabelle; Maddaluno, Jacques

    2012-01-01

    The aim of this review is to present the latest developments in the stereoselective synthesis of conjugated dienes, covering the period 2005-2010. Since the use of this class of compounds is linked to the nature of their appendages (aryls, alkyls, electron-withdrawing, and heterosubstituted groups), the review has been categorized accordingly and illustrates the most representative strategies and mechanisms to access these targets. PMID:22527407

  14. Stereoselective synthesis of unsaturated α-amino acids.

    PubMed

    Fanelli, Roberto; Jeanne-Julien, Louis; René, Adeline; Martinez, Jean; Cavelier, Florine

    2015-06-01

    Stereoselective synthesis of unsaturated α-amino acids was performed by asymmetric alkylation. Two methods were investigated and their enantiomeric excess measured and compared. The first route consisted of an enantioselective approach induced by the Corey-Lygo catalyst under chiral phase transfer conditions while the second one involved the hydroxypinanone chiral auxiliary, both implicating Schiff bases as substrate. In all cases, the use of a prochiral Schiff base gave higher enantiomeric excess and yield in the final desired amino acid. PMID:25715756

  15. Studies on the Synthesis of Reidispongiolide A: Stereoselective Synthesis of the C(22)-C(36) Fragment

    PubMed Central

    Ying, Maben; Roush, William R.

    2011-01-01

    A highly stereoselective synthesis of the C(22)-C(36) fragment 2 of reidispongiolide A is described. This synthesis features the highly stereoselective mismatched double asymmetric crotylboration reaction of the aldehyde derived from 5 and the new chiral reagent (S)-(E)-7 that provides 12 with >15:1 d.r. Subsequent coupling of the derived vinyl iodide 3 with aldehyde 16 provided allylic alcohol 17, that was elaborated by three steps into the targeted reidispongiolide fragment 2. PMID:22711935

  16. Titanium(IV)-Catalyzed Stereoselective Synthesis of Spirooxindole-1-pyrrolines

    PubMed Central

    2015-01-01

    A stereoselective cyclization between alkylidene oxindoles and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (as low as 5 mol %) to afford spiro[3,3′-oxindole-1-pyrrolines] in excellent yield (up to 99%) and diastereoselectivity (up to 99:1). Using a chiral scandium(III)–indapybox/BArF complex affords enantioenriched spirooxindole-1-pyrrolines where a ligand-induced reversal of diastereoselectivity is observed. This methodology is further demonstrated for the synthesis of pyrrolines from malonate alkylidene and coumarin derivatives. PMID:25474118

  17. Titanium(IV)-catalyzed stereoselective synthesis of spirooxindole-1-pyrrolines.

    PubMed

    Badillo, Joseph J; Ribeiro, Carlos J A; Olmstead, Marilyn M; Franz, Annaliese K

    2014-12-19

    A stereoselective cyclization between alkylidene oxindoles and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (as low as 5 mol %) to afford spiro[3,3'-oxindole-1-pyrrolines] in excellent yield (up to 99%) and diastereoselectivity (up to 99:1). Using a chiral scandium(III)-indapybox/BArF complex affords enantioenriched spirooxindole-1-pyrrolines where a ligand-induced reversal of diastereoselectivity is observed. This methodology is further demonstrated for the synthesis of pyrrolines from malonate alkylidene and coumarin derivatives. PMID:25474118

  18. Stereoselective Synthesis of Quaternary Proline Analogues

    PubMed Central

    Calaza, M. Isabel

    2009-01-01

    This review describes available methods for the diastereoselective and asymmetric synthesis of quaternary prolines. The focus is on the preparation of α-functionalized prolines with the pyrrolidine moiety not embedded in a polycyclic frame. The diverse synthetic approaches are classified according to the bond which is formed to complete the quaternary skeleton. PMID:19655047

  19. The stereoselective synthesis of dienes through dehalogenative homocoupling of terminal alkenyl bromides on Cu(110).

    PubMed

    Sun, Qiang; Cai, Liangliang; Ma, Honghong; Yuan, Chunxue; Xu, Wei

    2016-05-21

    We have successfully achieved the stereoselective synthesis of a specific cis-diene moiety through a dehalogenative homocoupling of alkenyl bromides on the Cu(110) surface, where the formation of a cis-form organometallic intermediate is the key to such a stereoselectivity as determined by DFT calculations. PMID:27063567

  20. Stereoselective Arene-Forming Aldol Condensation: Synthesis of Axially Chiral Aromatic Amides.

    PubMed

    Fäseke, Vincent C; Sparr, Christof

    2016-06-13

    The increasing awareness of the importance of amide atropisomers prompts the development of novel strategies for their selective preparation. Described herein is a method for the enantioselective synthesis of atropisomeric aromatic amides by an amine-catalyzed arene-forming aldol condensation. The high reactivity of the glyoxylic amide substrates enables a remarkably efficient construction of a new aromatic ring, which proceeds within minutes at ambient temperature to afford products with excellent stereoselectivity. The high rotational barriers of the reduced products highlight the utility of this stable, spatially organized chiral scaffold. PMID:27166995

  1. Stereoselective Arene-Forming Aldol Condensation: Synthesis of Configurationally Stable Oligo-1,2-naphthylenes.

    PubMed

    Lotter, Dominik; Neuburger, Markus; Rickhaus, Michel; Häussinger, Daniel; Sparr, Christof

    2016-02-18

    Structurally well-defined oligomers are fundamental for the functionality of natural molecular systems and key for the design of synthetic counterparts. Herein, we describe a strategy for the efficient synthesis of individual stereoisomers of 1,2-naphthylene oligomers by iterative building block additions and consecutive stereoselective arene-forming aldol condensation reactions. The catalyst-controlled atropoenantioselective and the substrate-controlled atropodiastereoselective aldol condensation reaction provide structurally distinct ter- and quaternaphthalene stereoisomers, which represent configurationally stable analogues of otherwise stereodynamic, helically shaped ortho-phenylenes. PMID:26799152

  2. Efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc) and sp(2)-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzyme.

    PubMed

    de la Fuente, Alex; Rísquez-Cuadro, Rocío; Verdaguer, Xavier; García Fernández, José M; Nanba, Eiji; Higaki, Katsumi; Ortiz Mellet, Carmen; Riera, Antoni

    2016-10-01

    Due to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy-iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta β-N-acetylglucosaminidase (β-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp(2)-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards β-hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidase. PMID:26564401

  3. Stereoselective synthesis of P-homochiral oligo(thymidine methanephosphonates).

    PubMed Central

    Lesnikowski, Z J; Jaworska, M; Stec, W J

    1988-01-01

    An approach to the stereoselective synthesis of P-homochiral oligo(thymidine methanephosphonates) is described. Fully protected (Rp)- and (Sp)-diastereomers of MMTrTPMeTAC (3) were prepared in the stereospecific reaction of P-chiral nucleotide component 5'-O-monomethoxytritylthymidine 3'-O-[O-(4-nitrophenyl)methanephosphonate] (1) and 3'-O-acetylthmydine (2) bearing activated 5'-hydroxyl function. Deprotection of the 5'-OH group in 3 and subsequent stepwise reactions of activated 5'-OH oligonucleotide components with (Rp)- or (Sp)- isomers of 1 gave the trinucleotide MMTrTPMeTPMeTAC (4) and, subsequently, the tetranucleotide MMTrTPMeTPMeTPMeTAC (5) possessing all (Rp)- or all (Sp)- configurations at their internucleotide methanephosphonate P-atoms. PMID:3211747

  4. Experimental and theoretical investigations of the stereoselective synthesis of p-stereogenic phosphine oxides.

    PubMed

    Copey, Laurent; Jean-Gérard, Ludivine; Framery, Eric; Pilet, Guillaume; Robert, Vincent; Andrioletti, Bruno

    2015-06-15

    An efficient enantioselective strategy for the synthesis of variously substituted phosphine oxides has been developed, incorporating the use of (1S,2S)-2-aminocyclohexanol as the chiral auxiliary. The method relies on three key steps: 1) Highly diastereoselective formation of P(V) oxazaphospholidine, rationalized by a theoretical study; 2) highly diastereoselective ring-opening of the oxazaphospholidine oxide with organometallic reagents that takes place with inversion of configuration at the P atom; 3) enantioselective synthesis of phosphine oxides by cleavage of the remaining P-O bond. Interestingly, the use of a P(III) phosphine precursor afforded a P-epimer oxazaphospholidine. Hence, the two enantiomeric phosphine oxides can be synthesized starting from either a P(V) or a P(III) phosphine precursor, which constitutes a clear advantage for the stereoselective synthesis of sterically hindered phosphine oxides. PMID:25980800

  5. Efficient and Stereoselective Dimerization of Pyrroloindolizine Derivatives Inspired by a Hypothesis for the Biosynthesis of Complex Myrmicarin Alkaloids

    PubMed Central

    Movassaghi, Mohammad; Ondrus, Alison E.; Chen, Bin

    2010-01-01

    Pyrroloindolizine derivatives participate in efficient and stereoselective homo- and heterodimerization reactions upon treatment with Brønsted or Lewis acids. The distinctive ability of pyrroloindolizines to act as azafulvenium ion precursors provides direct access to both heptacyclic and hexacyclic dimeric products. The inherent reactivity of these structures suggests a concise synthesis of complex myrmicarin alkaloids via dimerization of pyrroloindolizines, and may have implications for the biosynthesis of these intriguing alkaloids. PMID:18020368

  6. Total synthesis of bryostatins: the development of methodology for the atom-economic and stereoselective synthesis of the ring C subunit.

    PubMed

    Trost, Barry M; Frontier, Alison J; Thiel, Oliver R; Yang, Hanbiao; Dong, Guangbin

    2011-08-22

    Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for the stereoselective assembly of the ring C subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the ring C subunit of bryostatins. PMID:21793057

  7. Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

    PubMed Central

    Rigamonti, Marco Giulio

    2015-01-01

    Summary The first stereoselective synthesis of lippidulcines A, B and C has been accomplished starting from (+)-hernandulcin, which has been prepared on a multigram scale. The previously assigned absolute configurations have been confirmed. The key steps of this synthesis are based on a modified version of the Kornblum–DeLaMare rearrangement, and on a highly regioselective and stereoselective ketone reduction with the MeCBS reagent. The taste evaluations indicate that none of these sesquiterpenes are sweet, instead the lippidulcine A is a cooling agent with a mint after taste. PMID:26664632

  8. Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation.

    PubMed

    Rigamonti, Marco Giulio; Gatti, Francesco Gilberto

    2015-01-01

    The first stereoselective synthesis of lippidulcines A, B and C has been accomplished starting from (+)-hernandulcin, which has been prepared on a multigram scale. The previously assigned absolute configurations have been confirmed. The key steps of this synthesis are based on a modified version of the Kornblum-DeLaMare rearrangement, and on a highly regioselective and stereoselective ketone reduction with the MeCBS reagent. The taste evaluations indicate that none of these sesquiterpenes are sweet, instead the lippidulcine A is a cooling agent with a mint after taste. PMID:26664632

  9. Iron(III) chloride as an efficient catalyst for stereoselective synthesis of glycosyl azides and a cocatalyst with Cu(0) for the subsequent click chemistry.

    PubMed

    Salunke, Santosh B; Babu, N Seshu; Chen, Chien-Tien

    2011-10-01

    A highly efficient and mild method for azido glycosylation of glycosyl β-peracetates to 1,2-trans glycosyl azides was developed by using inexpensive FeCl(3) as the catalyst. In addition, we demonstrated, for the first time, that FeCl(3) in combination with copper powder can promote 1,3-dipolar cycloaddition (click chemistry) of azido glycosides with terminal alkynes. Good to excellent yields were obtained with exclusive formation of a single isomer in both glycosyl azidation and subsequent cycloaddition processes. PMID:21842053

  10. Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters.

    PubMed

    Engl, Oliver D; Fritz, Sven P; Wennemers, Helma

    2015-07-01

    Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin-derived N-Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto's catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/cholecystokinin-B receptor antagonist AG-041R. PMID:26033441

  11. Templated Oligosaccharide Synthesis: The Linker Effect on the Stereoselectivity of Glycosylation

    PubMed Central

    Pornsuriyasak, Papapida; Jia, Xiao G.; Kaeothip, Sophon; Demchenko, Alexei V.

    2016-01-01

    A new method for intramolecular oligosaccharide synthesis that is conceptually related to the general molecular clamp approach is introduced. Exceptional α-selectivity has been achieved in a majority of applications. Unlike other related concepts, this approach is based on the bisphenol A template, which allows one to connect multiple building blocks to perform templated oligosaccharide synthesis with complete stereoselectivity. This principle was demonstrated by the synthesis of an α,α-linked trisaccharide. PMID:27115718

  12. Recent Progress on the Stereoselective Synthesis of Cyclic Quaternary α-Amino Acids

    PubMed Central

    Cativiela, Carlos; Ordóñez, Mario

    2010-01-01

    The most recent papers describing the stereoselective synthesis of cyclic quaternary α-amino acids are collected in this review. The diverse synthetic approaches are classified according to the size of the ring and taking into account the bond that is formed to complete the quaternary skeleton. PMID:20300486

  13. Stereoselective total synthesis of (-)-perrottetinene and assignment of its absolute configuration.

    PubMed

    Song, Yanling; Hwang, Soonho; Gong, Ping; Kim, Deukjoon; Kim, Sanghee

    2008-01-17

    The first stereoselective total synthesis of the bibenzyl tetrahydrocannabinol, (-)-perrottetinene, has been achieved from readily available starting materials. The absolute stereochemistry is derived from a chiral gamma-hydroxy vinylstannane. The key reaction is the synthesis of the cis-disubstituted cyclohexene ring of perrottetinene by diastereoselective Ireland-Claisen rearrangement and a ring-closing metathesis reaction. The absolute configuration of (-)-perrottetinene is proposed. PMID:18085788

  14. Stereoselective Synthesis of (R)-3-Methylthalidomide by Piperidin-2-one Ring Assembly Approach.

    PubMed

    Yadav, Shyam Raj; Tiwari, Vinay Shankar; Haq, Wahajul

    2015-09-01

    A simple and stereoselective synthesis of 3-methylthalidomide, a configurationally stable thalidomide analog, is presented. Herein we describe the synthesis of (R)-3-methylthalidomide starting from (S)-alanine by piperidin-2-one ring assembly approach in high yield and enantiomeric purity without using a chiral auxiliary or reagent. Starting from (R)-alanine, the corresponding (S)-3-methylthalidomide can be prepared using the same methodology. PMID:26079113

  15. Stereoselective synthesis of desloratadine derivatives as antagonist of histamine.

    PubMed

    Liu, Gai-Zhi; Xu, Hai-Wei; Chen, Guang-Wei; Wang, Peng; Wang, Ya-Na; Liu, Hong-Min; Yu, De-Quan

    2010-02-15

    A series of desloratadine derivatives were stereoselectively synthesized and evaluated for H(1) antihistamine activity. For the evaluation of H(1) antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. The synthesized desloratadine derivatives 7, 8 and 9 are structurally related to rupatadine and were generated by replacement of the 5-methyl-3-pyridine group of rupatadine with gamma-alkylidene butenolide. Their H(1) antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7, 8a and 8g display potent activity inhibiting histamine-induced effects. PMID:20110173

  16. Stereoselectively synthesis and structural confirmation of dehydrodipeptides with dehydrobutyrine.

    PubMed

    Tian, Xia; Li, Linna; Han, Jianrong; Zhen, Xiaoli; Liu, Shouxin

    2016-01-01

    Most of polypeptides containing α,β-dehydroamino acids have important biological activity, so exploration of synthetic method has practical significance. In this paper, dipeptides were prepared from l-threonine by protecting of c-terminal allyl acetate, and condensing reaction with a series of N-Boc amino acid. Then, treatment of dipeptides obtained with DMAP, (Boc)2O and tetramethylguanidine in the acetonitrile occured β-elimination reaction to yield stereoselectively dehydrodipeptides. Structures of dehydrodipeptides were confirmed by (1)H NMR, (13)C NMR and MS. Analysis of (1)H NMR, 2D NMR and crystal structure showed that the dehydrodipeptides were Z-configuration.Graphical abstractDehydrodipeptides were prepared from l-threonine. Their structures were confirmed by (1)H NMR, (13)C NMR and MS. PMID:27047726

  17. Stereoselective Synthesis of Isochromanones by an Asymmetric Ortho-Lithiation Strategy: Synthetic Access to the Isochromanone Core of the Ajudazols.

    PubMed

    Essig, Sebastian; Menche, Dirk

    2016-03-01

    Full details on the design, development, and application of a highly stereoselective strategy for the synthesis of isochromanones are reported. The method is based on an asymmetric ortho lithiation with aldehyde electrophiles and utilizes the chiral memory of a preoriented atropisomeric amide axis for stereocontrol. For direct transformation of sterically hindered amides to isochromanones, efficient and mild one-pot protocols involving either O-alkylation or acidic microwave activation were developed. The procedures may be applied also to highly functionalized as well as stereochemically complex and sensitive substrates and demonstrate a high protective group tolerance. Furthermore, asymmetric crotylborations of axially chiral amides were studied in detail. These methodologies enable a general access to all possible stereoisomers of hydroxyl-isochromanones with up to three contiguous stereocenters. The true applicability of our approach was finally demonstrated by synthesis of the authentic anti,anti-configured isochromanone core of the ajudazols, highly potent inhibitors of the mitochondrial respiratory chain from myxobacteria. PMID:26824669

  18. Stereoselective terminal functionalization of small peptides for catalytic asymmetric synthesis of unnatural peptides

    PubMed Central

    Maruoka, Keiji; Tayama, Eiji; Ooi, Takashi

    2004-01-01

    The asymmetric phase-transfer catalytic alkylation of peptides has been achieved by the use of designed C2-symmetric chiral quaternary ammonium bromide 1 as catalyst. Excellent stereoselectivities were uniformly observed in the alkylation with a variety of alkyl halides and the efficiency of the transmission of stereochemical information was not affected by the side-chain structure of the preexisting amino acid residues. This method also enables an asymmetric construction of noncoded α,α-dialkyl-α-amino acid residues at the peptide terminal. Since this chirality can be efficiently transferred to the adjacent amino acid moiety, our approach provides a general procedure not only for the highly stereoselective terminal functionalization of peptides but also for the sequential asymmetric construction of unnatural oligopeptides, which should play a vital role in the peptide-based drug discovery process. PMID:15079083

  19. The stereoselective synthesis of α-amino aldols starting from terminal alkynes.

    PubMed

    Miura, Tomoya; Nakamuro, Takayuki; Hiraga, Kentaro; Murakami, Masahiro

    2014-09-18

    A new procedure for the stereoselective synthesis of syn α-amino β-oxy ketones is reported. It consists of two steps; in the first step, α-amino silyl enol ethers having a (Z) geometry are prepared from 1-alkynes via 1-sulfonyl-1,2,3-triazoles. In the second step, the silyl enol ethers undergo the TiCl4-mediated Mukaiyama aldol reaction with aldehydes to produce α-amino β-oxy ketones with excellent syn-selectivity. PMID:25068433

  20. Synthesis of α-Chiral Butyrolactones by Highly Stereoselective Radical Transfer or Sequential Asymmetric Alkylations: Concise Preparation of Leupyrrin Moieties.

    PubMed

    Schrempp, Michael; Thiede, Sebastian; Herkommer, Daniel; Gansäuer, Andreas; Menche, Dirk

    2015-11-01

    Inspired by the bioactive natural metabolites leupyrrin A1 and B1 , two novel stereoselective methods for the highly concise synthesis of densely substituted α-chiral butyrolactones are reported. The first approach relies on an innovative three-step Ti(III) -catalyzed radical reaction that proceeds with excellent chemo-, regio-, and stereoselectivity. The alternative route utilizes sequential asymmetric alkylations and enables asymmetric synthesis of the authentic α-tetrasubstituted butyrolactone motif of the leupyrrins in only four steps from commercially available substrates. PMID:26354047

  1. Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; a Virulence Factor of Mycobacterium tuberculosis.

    PubMed

    Buter, Jeffrey; Heijnen, Dorus; Wan, Ieng Chim; Bickelhaupt, F Matthias; Young, David C; Otten, Edwin; Moody, D Branch; Minnaard, Adriaan J

    2016-08-01

    Despite its status as one of the world's most prevalent and deadly bacterial pathogens, Mycobacterium tuberculosis (Mtb) infection is not routinely diagnosed by rapid and highly reliable tests. A program to discover Mtb-specific biomarkers recently identified two natural compounds, 1-tuberculosinyl adenosine (1-TbAd) and N(6)-tuberculosinyl adenosine (N(6)-TbAd). Based on their association with virulence, the lack of similar compounds in nature, the presence of multiple stereocenters, and the need for abundant products to develop diagnostic tests, synthesis of these compounds was considered to be of high value but challenging. Here, a multigram-scale stereoselective synthesis of 1-TbAd and N(6)-TbAd is described. As a key-step, a chiral auxiliary-mediated Diels-Alder cycloaddition was developed, introducing the three stereocenters with a high exo endo ratio (10:1) and excellent enantioselectivity (>98% ee). This constitutes the first entry into the stereoselective synthesis of diterpenes with the halimane skeleton. Computational studies explain the observed stereochemical outcome. PMID:27398789

  2. Stereoselective synthesis of stable-isotope-labeled amino acids

    SciTech Connect

    Unkefer, C.J.; Martinez, R.A.; Silks, L.A. III; Lodwig, S.N.

    1994-12-01

    For magnetic resonance and vibrational spectroscopies to reach their full potential, they must be used in combination with sophisticated site-specific stable isotope labeling of biological macromolecules. Labeled amino acids are required for the study of the structure and function of enzymes and proteins. Because there are 20 common amino acids, each with its own distinguishing chemistry, they remain a synthetic challenge. The Oppolzer chiral auxiliary provides a general tool with which to approach the synthesis of labeled amino acids. By using the Oppolzer auxiliary, amino acids can be constructed from several small molecules, which is ideal for stable isotope labeling. In addition to directing the stereochemistry at the {alpha}-carbon, the camphorsultam can be used for stereo-specific isotope labeling at prochiral centers in amino acids. By using the camphorsultam auxiliary we have the potential to synthesize virtually any isotopomer of all of the common amino acids.

  3. Stereoselective 6-exo radical cyclization using cis-vinyl sulfoxide: practical total synthesis of CTX3C.

    PubMed

    Yamashita, Shuji; Ishihara, Yuuki; Morita, Hiroyuki; Uchiyama, Junichi; Takeuchi, Katsutoshi; Inoue, Masayuki; Hirama, Masahiro

    2011-03-25

    Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers. We report a highly stereoselective 6-exo radical cyclization/ring-closing olefin metathesis sequence to construct the syn/trans-fused polyether system. The new method was applied to the practical synthesis of ciguatoxin CTX3C. PMID:21250701

  4. A stereoselective synthesis of (+)-physoperuvine using a tandem aza-Claisen rearrangement and ring closing metathesis reaction.

    PubMed

    Zaed, Ahmed M; Swift, Michael D; Sutherland, Andrew

    2009-07-01

    A stereoselective synthesis of (+)-physoperuvine, a tropane alkaloid from Physalis peruviana Linne has been developed using a one-pot tandem aza-Claisen rearrangement and ring closing metathesis reaction to form the key amino-substituted cycloheptene ring. PMID:19532981

  5. Stereoselective Synthesis of α-Amino-C-phosphinic Acids and Derivatives.

    PubMed

    Viveros-Ceballos, José Luis; Ordóñez, Mario; Sayago, Francisco J; Cativiela, Carlos

    2016-01-01

    α-Amino-C-phosphinic acids and derivatives are an important group of compounds of synthetic and medicinal interest and particular attention has been dedicated to their stereoselective synthesis in recent years. Among these, phosphinic pseudopeptides have acquired pharmacological importance in influencing physiologic and pathologic processes, primarily acting as inhibitors for proteolytic enzymes where molecular stereochemistry has proven to be critical. This review summarizes the latest developments in the asymmetric synthesis of acyclic and phosphacyclic α-amino-C-phosphinic acids and derivatives, following in the first case an order according to the strategy used, whereas for cyclic compounds the nitrogen embedding in the heterocyclic core is considered. In addition selected examples of pharmacological implications of title compounds are also disclosed. PMID:27589703

  6. Stereoselective Alkylation of the Vinylketene Silyl N,O-Acetal and Its Application to the Synthesis of Mycocerosic Acid.

    PubMed

    Nakamura, Tatsuya; Kubota, Kei; Ieki, Takanori; Hosokawa, Seijiro

    2016-01-01

    Stereoselective alkylation of the vinylketene silyl N,O-acetal possessing a chiral auxiliary has been achieved by using activated alkyl halides including allyl iodides, benzyl iodides, and propargyl iodide with Ag(I) ion in the presence of BF3·OEt2. The reaction proceeded to give reduced polyketides in high stereoselectivity. The synthesis of mycocerosic acid, a component of the cell envelope of Mycobacterium tuberculosis, has been accomplished by this methodology. During the synthetic studies, 2-methylbenzimidazole was found to be a bulky proton source which worked in the presence of liquid ammonia. PMID:26673532

  7. NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

    PubMed Central

    Schmidtgall, Boris; Höbartner, Claudia

    2015-01-01

    Summary Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T–T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X–T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A–T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues. PMID:25670992

  8. NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A-T phosphoramidite building blocks.

    PubMed

    Schmidtgall, Boris; Höbartner, Claudia; Ducho, Christian

    2015-01-01

    Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T-T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X-T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A-T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues. PMID:25670992

  9. Stereoselective synthesis of the C1-C29 part of amphidinol 3.

    PubMed

    Tsuruda, Takeshi; Ebine, Makoto; Umeda, Aya; Oishi, Tohru

    2015-01-16

    Stereoselective synthesis of the C1-C29 part of amphidinol 3 (AM3) was achieved. The C1-C20 part was assembled from three building blocks via regioselective cross metathesis to form the C4-C5 double bond and addition of an alkenyllithium and a lithium acetylide to two Weinreb amides followed by asymmetric reduction to form the C9-C10 and C14-C15 bonds, respectively. The C21-C29 part was synthesized via successive cross metathesis and oxa-Michael addition sequence to construct the 1,3-diol system at C25 and C27 and Brown asymmetric crotylation to introduce the stereogenic centers at C23 and C24. Coupling of the C1-C20 and C21-C29 parts was achieved by Julia-Kocienski olefination and regio- and stereoselective dihydroxylation of the C20-C21 double bond in the presence of the C4-C5 and C8-C9 double bonds to afford the C1-C29 part of AM3. PMID:25517178

  10. Silyllithium-Initiated Coupling of α-Ketoamides with tert-Butanesulfinylimines for Stereoselective Synthesis of Enantioenriched α-(Silyloxy)-β-amino Amides.

    PubMed

    Sun, Zhao; Liu, Hui; Zeng, Yong-Ming; Lu, Chong-Dao; Xu, Yan-Jun

    2016-02-01

    A silyllithium-initiated coupling of α-ketoamides with tert-butanesulfinylimines was developed for the efficient, stereoselective synthesis of enantioenriched α-(silyloxy)-β-amino amides. Nucleophilic addition of silyllithium to α-ketoamides, followed by 1,2-Brook rearrangement, generates nucleophilic enolates, which are then intercepted by chiral imines to provide three-component coupling products. Use of α-ketoamides is critical for achieving high yields and diastereoselectivities in the resulting α-hydroxy-β-amino acid derivatives. PMID:26809848

  11. Stereoselective Total Synthesis of Atractylodemayne A, a Conjugated 2(E),8(Z),10(E)-Triene-4,6-diyne.

    PubMed

    Schmidt, Bernd; Audörsch, Stephan

    2016-03-01

    The first total synthesis of the polyacetylene natural product atractylodemayne A is reported. Stereoselective construction of the conjugated 8(Z),10(E)-diene moiety was achieved through a tethered ring-closing metathesis approach, comprising a Ru-catalyzed RCM followed by a base-induced elimination. A Pd-catalyzed Cadiot-Chodkiewicz coupling was used for the synthesis of the diyne. Overall, atractylodemayne A was synthesized in nine steps for the longest linear sequence. PMID:26886865

  12. Stereoselective Construction of β-Mannopyranosides by Anomeric O-Alkylation: Synthesis of the Trisaccharide Core of N-linked Glycans.

    PubMed

    Nguyen, Hai; Zhu, Danyang; Li, Xiaohua; Zhu, Jianglong

    2016-04-01

    A new and efficient approach for direct and stereoselective synthesis of β-mannopyranosides by anomeric O-alkylation has been developed. This anomeric O-alkylation of mannopyranose-derived lactols is proposed to occur under synergistic control of a kinetic anomeric effect and metal chelation. The presence of a conformationally flexible C6 oxygen atom in the sugar-derived lactol donors is required for this anomeric O-alkylation to be efficient, probably because of its chelation with cesium ion. In contrast, the presence of a C2 oxygen atom plays a minor role. This glycosylation method has been successfully utilized for the synthesis of the trisaccharide core of complex N-linked glycans. PMID:26948686

  13. Stereoselective Synthesis of 1,3-Diaminotruxillic Acid Derivatives: An Advantageous Combination of C-H-ortho-Palladation and On-Flow [2+2]-Photocycloaddition in Microreactors.

    PubMed

    Serrano, Elena; Juan, Alberto; García-Montero, Angel; Soler, Tatiana; Jiménez-Márquez, Francisco; Cativiela, Carlos; Gomez, M Victoria; Urriolabeitia, Esteban P

    2016-01-01

    The stereoselective synthesis of ε-isomers of dimethyl esters of 1,3-diaminotruxillic acid in three steps is reported. The first step is the ortho-palladation of (Z)-2-aryl-4-aryliden-5(4H)-oxazolones 1 to give dinuclear complexes 2 with bridging carboxylates. The reaction occurs through regioselective activation of the ortho-CH bond of the 4-arylidene ring in carboxylic acids. The second step is the [2+2]-photocycloaddition of the CC exocyclic bonds of the oxazolone skeleton in 2 to afford the corresponding dinuclear ortho-palladated cyclobutanes 3. This key step was performed very efficiently by using LED light sources with different wavelengths (465, 525 or 625 nm) in flow microreactors. The final step involved the depalladation of 3 by hydrogenation in methanol to afford the ε-1,3-diaminotruxillic acid derivatives as single isomers. PMID:26597315

  14. On the Stereoselective Synthesis of (+)-Pinoresinol in Forsythia Suspensa from its Achiral Precursor, Coniferyl Alcohol

    NASA Technical Reports Server (NTRS)

    Davin, Laurence B.; Bedgar, Diana L.; Katayama, Takeshi; Lewis, Norman G.

    1992-01-01

    The residue from Forsythia suspensa stems, upon removal of soluble enzymes, has provided the first evidence for a stereoselective coupling enzyme in lignan biosynthesis. This preparation catalyses the preferred formation (ca 65%) of (+)-[8,8'- C-14] pinoresinol from [8-C-14]coniferyl alcohol in the absence of exogenously provided cofactors; addition of H2O2 had little effect on enantiomeric composition. However, when NAD and malate were supplied, the stereoselectivity of the coupling reaction was significantly enhanced and pinoresinol consisting of ca 80% of the (+)-antipode was obtained. Clearly, the insoluble residue contains a specific coupling enzyme which catalyses (+)-pinoresinol formation from coniferyl alcohol. By contrast, when [8- C-14] sinapyl alcohol was employed as substrate, only racemic syringaresinols were formed: this non-stereoselective peroxidase-catalysed coupling reaction presumably accounts for the low levels of (-)-pinoresinol encountered in this system when coniferyl alcohol is used as a substrate.

  15. Stereoselective Electrophilic Cyclization.

    PubMed

    Sakakura, Akira; Ishihara, Kazuaki

    2015-08-01

    Electrophilic cyclizations of unactivated alkenes play highly important roles in the synthesis of useful building blocks. This account describes our contributions to the rational design of monofunctionalized chiral Lewis base catalysts for enantioselective iodo- and protocyclizations. For the stereoselective promotion of electrophilic bromocyclizations, nucleophilic phosphite-urea cooperative catalysts have been designed. PMID:26147781

  16. Stereoselective synthesis of (Z)-13-hexadecen-11-yn-1-yl acetate, the major component of the sex pheromone of the pine processionary moth (Thaumetopoea pityocampa).

    PubMed

    Shani, A; Klug, J T; Skorka, J

    1983-07-01

    A short and stereoselective synthesis of (Z)-13-hexadecen-1 1-yn-1-yl acetate is described. The main feature is a low-temperature Wittig reaction of a triphenylpropylphosphonium bromide with a long-chain alkylated propargyl aldehyde. PMID:24407758

  17. Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

    PubMed Central

    Zimmermann, Nicole; Hilgraf, Robert; Lehmann, Lutz; Ibarra, Daniel

    2012-01-01

    Summary Starting from the enantiomers of limonene, all eight stereoisomers of trans-fused dihydronepetalactones were synthesized. Key compounds were pure stereoisomers of 1-acetoxymethyl-2-methyl-5-(2-hydroxy-1-methylethyl)-1-cyclopentene. The stereogenic center of limonene was retained at position 4a of the target compounds and used to stereoselectively control the introduction of the other chiral centers during the synthesis. Basically, this approach could also be used for the synthesis of enantiomerically pure trans-fused iridomyrmecins. Using synthetic reference samples, the combination of enantioselective gas chromatography and mass spectrometry revealed that volatiles released by the endohyperparasitoid wasp Alloxysta victrix contain the enantiomerically pure trans-fused (4R,4aR,7R,7aS)-dihydronepetalactone as a minor component, showing an unusual (R)-configured stereogenic center at position 7. PMID:23019455

  18. Copper mediated stereoselective synthesis of C-glycosides from unactivated alkynes.

    PubMed

    Kusunuru, Anil Kumar; Tatina, Madhubabu; Yousuf, Syed Khalid; Mukherjee, Debaraj

    2013-10-01

    A highly stereoselective rapid C-glycosylation reaction has been developed between glycal and unactivated alkynes in the presence of coppertriflate and ascorbic acid at low catalyst loading and at room temperature. A wide variety of glycals and aryl acetylenes participate in the reaction smoothly. TfOH generated during the reduction of Cu(OTf)2 by ascorbic acid may be the active catalyst for the glycosylation. PMID:24049771

  19. Stereoselective synthesis of tetrasubstituted alkenes via a sequential carbocupration and a new sulfur–lithium exchange

    PubMed Central

    Unsinn, Andreas; Dunst, Cora

    2012-01-01

    Summary We have designed a new sequential carbocupration and sulfur–lithium exchange that leads stereo- and regioselectively to trisubstituted alkenyllithiums. Subsequent trapping with various electrophiles yields tetrasubstituted olefins with good control of the double-bond geometry (E/Z ratio up to 99:1). The novel sulfur–lithium exchange could be extended to the stereoselective preparation of Z-styryl lithium derivatives with almost complete retention of the double-bond geometry. PMID:23365630

  20. Selective carbon-carbon bond cleavage for the stereoselective synthesis of acyclic systems.

    PubMed

    Marek, Ilan; Masarwa, Ahmad; Delaye, Pierre-Olivier; Leibeling, Markus

    2015-01-01

    Most of the efforts of organic chemists have been directed to the development of creative strategies to build carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. In this Review, we show an alternative approach where challenging molecular skeletons could be prepared through selective cleavage of carbon-carbon bonds. We demonstrate that it has the potential to be a general principle in organic synthesis for the regio-, diastereo-, and even enantioselective preparation of adducts despite the fact that C-C single bonds are among the least reactive functional groups. The development of such strategies may have an impact on synthesis design and can ultimately lead to new selective and efficient processes for the utilization of simple hydrocarbons. PMID:25266824

  1. Ligand-Enabled, Copper-Catalyzed Regio- and Stereoselective Synthesis of Trialkylsubstituted Alkenylboronates from Unactivated Internal Alkynes.

    PubMed

    Itoh, Taisuke; Shimizu, Yohei; Kanai, Motomu

    2016-06-22

    We report the first copper-catalyzed regio- and stereoselective borylalkylation of dialkylsubstituted internal alkynes with bis(pinacolato)diboron and alkyl halides. A catalytically generated borylcopper species containing a novel π-accepting N-heterocyclic carbene ligand chemoselectively reacted with unactivated internal alkynes over alkyl halides. The intermediate alkenylcopper species subsequently reacted with alkyl halides, affording the desired products. The copper catalyst differentiated steric demands between the two aliphatic substituents on the C≡C triple bond of the alkyne substrates to exhibit high regioselectivity from a wide range of alkyne/alkyl halide combinations. This method is useful for the straightforward synthesis of trialkylsubstituted alkenylboronates, i.e., versatile precursors for tetrasubstituted alkenes containing three or four different alkylsubstituents, which are difficult to synthesize by other methods. PMID:27269988

  2. Stereoselectivity in Polyphenol Biosynthesis

    NASA Technical Reports Server (NTRS)

    Lewis, Norman G.; Davin, Laurence B.

    1992-01-01

    Stereoselectivity plays an important role in the late stages of phenyl-propanoid metabolism, affording lignins, lignans, and neolignans. Stereoselectivity is manifested during monolignol (glucoside) synthesis, e.g., where the geometry (E or Z) of the pendant double bond affects the specificity of UDPG:coniferyl alcohol glucosyltransferases in different species. Such findings are viewed to have important ramifications in monolignol transport and storage processes, with roles for both E- and Z-monolignols and their glucosides in lignin/lignan biosynthesis being envisaged. Stereoselectivity is also of great importance in enantiose-lective enzymatic processes affording optically active lignans. Thus, cell-free extracts from Forsythia species were demonstrated to synthesize the enantiomerically pure lignans, (-)-secoisolariciresinol, and (-)-pinoresinol, when NAD(P)H, H2O2 and E-coniferyl alcohol were added. Progress toward elucidating the enzymatic steps involved in such highly stereoselective processes is discussed. Also described are preliminary studies aimed at developing methodologies to determine the subcellular location of late-stage phenylpropanoid metabolites (e.g., coniferyl alcohol) and key enzymes thereof, in intact tissue or cells. This knowledge is essential if questions regarding lignin and lignan tissue specificity and regulation of these processes are to be deciphered.

  3. Stereoselective Synthesis of Saturated Heterocycles via Pd-Catalyzed Alkene Carboetherification and Carboamination Reactions

    PubMed Central

    Wolfe, John P.

    2009-01-01

    The development of Pd-catalyzed carboetherification and carboamination reactions between aryl/alkenyl halides and alkenes bearing pendant heteroatoms is described. These transformations effect the stereoselective construction of useful heterocycles such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines, and piperazines. The scope, limitations, and applications of these reactions are presented, and current stereochemical models are described. The mechanism of product formation, which involves an unusual intramolecular syn-insertion of an alkene into a Pd-Heteroatom bond is also discussed in detail. PMID:19183704

  4. New stereoselective titanium reductive amination synthesis of 3-amino and polyaminosterol derivatives possessing antimicrobial activities.

    PubMed

    Salmi, Chanaz; Loncle, Celine; Vidal, Nicolas; Letourneux, Yves; Brunel, Jean Michel

    2008-03-01

    A series of 3-amino and polyaminosterol analogues of squalamine and trodusquemine were synthesized involving a new stereoselective titanium reductive amination reaction in high chemical yields of up to 95% in numerous cases. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. Activity was highly dependent on the different compounds' structures involved and best results have been obtained with aminosterol derivatives 4b, 4e and 6i exhibiting activities against yeasts, Gram positive and Gram negative bacteria at average concentrations of 6.25-12.5 microg/mL. PMID:17566609

  5. Stereoselective synthesis of γ-hydroxynorvaline through combination of organo- and biocatalysis.

    PubMed

    Simon, Robert C; Busto, Eduardo; Schrittwieser, Joerg H; Sattler, Johann H; Pietruszka, Jörg; Faber, Kurt; Kroutil, Wolfgang

    2014-12-25

    An efficient route for the synthesis of all four diastereomers of PMP-protected α-amino-γ-butyrolacton to access γ-hydroxynorvaline was established. The asymmetric key steps comprise an organocatalytic Mannich reaction and an enzymatic ketone reduction. Three reaction steps could be integrated in a one-pot process, using 2-PrOH both as solvent and as reducing agent. The sequential construction of stereogenic centres gave access to each of the four stereoisomers in high yield and with excellent stereocontrol. PMID:25251725

  6. A stereoselective and short total synthesis of the polyhydroxylated gamma-amino acid (-)-detoxinine, based on stereoselective preparation of dihydropyrrole derivatives from lithiated alkoxyallenes.

    PubMed

    Flögel, Oliver; Okala Amombo, Marlyse Ghislaine; Reissig, Hans-Ulrich; Zahn, Gernot; Brüdgam, Irene; Hartl, Hans

    2003-03-17

    Based on our earlier results employing lithiated methoxyallene 2 as C(3) building block and imines 3 for the synthesis of dihydropyrrole derivatives 5, we have investigated chiral imines 6, 10, and 15 as electrophilic components. Combined with lithiated alkoxyallenes, these imines provide the corresponding primary adducts and finally the dihydropyrrole derivatives 8, 12, 17, 20, and 22 in good yields and with high to excellent syn selectivities. This stereochemical outcome is interpreted as a result of alpha-chelate control. Treatment with hydrochloric acid converted syn-8 and syn-12 into bicyclic compounds 9 and 13, whereas under more mildly acidic conditions adduct syn-17 was transformed into diol syn-18. The total synthesis of the uncommon gamma-amino acid (-)-detoxinine could be achieved by starting from (S)-malic acid, which was converted into imine 15 in four steps. Lithiated benzyloxyallene added to imine 15 and efficiently furnished the crucial dihydropyrrole derivative syn-22. The hydrogenolysis of this compound did not directly provide the protected triol 29 as anticipated, but a stepwise protocol made the triol available in a fairly satisfactory manner. A second crucial step of the synthesis was the selective oxidation of 29, which could be achieved by employing platinum dioxide and oxygen. The resulting bicyclic lactone 30 was smoothly transformed into enantiopure (-)-detoxinine. Thus, a fairly short synthesis of this natural product based on a lithiated alkoxyallene could be performed, demonstrating the potential of these intermediates for syntheses of interesting functionalized heterocyclic compounds. PMID:12645030

  7. A highly stereoselective synthesis of C-24 and C-25 oxysterols from desmosterol.

    PubMed

    Zhao, Qian; Qian, Chao; Chen, Xin-Zhi

    2016-05-01

    A new highly stereoselective construction of the side chain of the C-24 and C-25 oxysterols has been achieved by using desmosterol acetate as the starting material and an improved Sharpless catalytic asymmetric dihydroxylation with 100% d.e. (diastereomeric excess) as the key step. The result is much better than the usual asymmetric dihydroxylation procedure. t-Butyl nitrite/2,2,6,6-tetramethylpiperidine N-oxyl radical/FeCl3 catalyst system was developed to activate molecular oxygen for the aerobic oxidation of 24-hydroxycholesterol and the 24-ketocholesterol was obtained in 86.2% yield. The oxidation system has never been reported before. The mechanism for the catalytic aerobic oxidation was also proposed. PMID:26968128

  8. Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity.

    PubMed

    Stavrinides, Anna; Tatsis, Evangelos C; Caputi, Lorenzo; Foureau, Emilien; Stevenson, Clare E M; Lawson, David M; Courdavault, Vincent; O'Connor, Sarah E

    2016-01-01

    Plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. These changes in stereochemistry dramatically impact biological activity. Notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. We reported a medium chain dehydrogenase/reductase (MDR) from Catharanthus roseus that catalyses formation of a heteroyohimbine isomer. Here we report the discovery of additional heteroyohimbine synthases (HYSs), one of which produces a mixture of diastereomers. The crystal structures for three HYSs have been solved, providing insight into the mechanism of reactivity and stereoselectivity, with mutation of one loop transforming product specificity. Localization and gene silencing experiments provide a basis for understanding the function of these enzymes in vivo. This work sets the stage to explore how MDRs evolved to generate structural and biological diversity in specialized plant metabolism and opens the possibility for metabolic engineering of new compounds based on this scaffold. PMID:27418042

  9. Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity

    PubMed Central

    Stavrinides, Anna; Tatsis, Evangelos C.; Caputi, Lorenzo; Foureau, Emilien; Stevenson, Clare E. M.; Lawson, David M.; Courdavault, Vincent; O'Connor, Sarah E.

    2016-01-01

    Plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. These changes in stereochemistry dramatically impact biological activity. Notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. We reported a medium chain dehydrogenase/reductase (MDR) from Catharanthus roseus that catalyses formation of a heteroyohimbine isomer. Here we report the discovery of additional heteroyohimbine synthases (HYSs), one of which produces a mixture of diastereomers. The crystal structures for three HYSs have been solved, providing insight into the mechanism of reactivity and stereoselectivity, with mutation of one loop transforming product specificity. Localization and gene silencing experiments provide a basis for understanding the function of these enzymes in vivo. This work sets the stage to explore how MDRs evolved to generate structural and biological diversity in specialized plant metabolism and opens the possibility for metabolic engineering of new compounds based on this scaffold. PMID:27418042

  10. Stereoselective synthesis of (E)-trisubstituted alpha,beta-unsaturated amides and acids.

    PubMed

    Feuillet, Fred J P; Cheeseman, Matt; Mahon, Mary F; Bull, Steven D

    2005-08-21

    Potassium alkoxides of N-acyl-oxazolidin-2-one-syn-aldols undergo stereoselective elimination reactions to afford a range of trisubstituted (E)-alpha,beta-unsaturated amides in >95% de, that may be subsequently converted into their corresponding (E)-alpha,beta-unsaturated acids or (E)-alpha,beta-unsaturated oxazolines in good yield. syn-Aldols derived from alpha,beta-unsaturated aldehydes gave their corresponding trisubstituted (E)-alpha,beta-unsaturated-amides with poorer levels of diastereocontrol, whilst there was a similar loss in (E)-selectivity during elimination of syn-aldols derived from chiral aldehydes. These elimination reactions proceed via rearrangement of the potassium alkoxide of the syn-aldol to a 1,3-oxazinane-2,4-dione enolate intermediate that subsequently eliminates carbon dioxide to afford a trisubstituted (E)-alpha,beta-unsaturated amide. The (E)-selectivity observed during the E1cB-type elimination step has been rationalised using a simple conformational model that employs a chair-like transition state to explain the observed stereocontrol. PMID:16186928

  11. Regio- and Stereoselective Synthesis of Spiropyrrolizidines and Piperazines through Azomethine Ylide Cycloaddition Reaction.

    PubMed

    Haddad, Saoussen; Boudriga, Sarra; Porzio, François; Soldera, Armand; Askri, Moheddine; Knorr, Michael; Rousselin, Yoann; Kubicki, Marek M; Golz, Christopher; Strohmann, Carsten

    2015-09-18

    A series of original spiropyrrolizidine derivatives has been prepared by a one-pot three-component [3 + 2] cycloaddition reaction of (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-diones, l-proline, and the cyclic ketones 1H-indole-2,3-dione (isatin), indenoquinoxaline-11-one and acenaphthenequinone. We disclose an unprecedented isomerization of some spiroadducts leading to a new family of spirooxindolepyrrolizidines. Furthermore, these cycloadducts underwent retro-1,3-dipolar cycloaddition yielding unexpected regioisomers. Upon treatment of the dipolarophiles with in situ generated azomethine ylides from l-proline or acenaphthenequinone, formation of spiroadducts and unusual polycyclic fused piperazines through a stepwise [3 + 3] cycloaddition pathway is observed. The stereochemistry of these N-heterocycles has been confirmed by several X-ray diffraction studies. Some of these compounds exhibit extensive hydrogen bonding in the crystalline state. To enlighten the observed regio- and stereoselectivity of the [3 + 2] cycloaddition, calculations using the DFT approach at the B3LYP/6-31G(d,p) level were carried out. It was found that this reaction is under kinetic control. PMID:26291879

  12. Stereoselective Synthesis and Retentive Trapping of α-Chiral Secondary Alkyllithiums Leading to Stereodefined α,β-Dimethyl Carboxylic Esters.

    PubMed

    Morozova, Varvara; Moriya, Kohei; Mayer, Peter; Knochel, Paul

    2016-07-11

    The treatment of α-chiral secondary alkyl iodides with tBuLi at -100 °C leads to the corresponding secondary alkyllithiums with high retention of configuration. Subsequent quenching with various electrophiles such as Bu2 S2 , DMF, MeOB(OR)2 , or Et2 CO provides the desired products with retention of configuration. Furthermore, a transmetalation with CuBr⋅P(OEt)3 also allows retentive trapping with acid chlorides and ethylene oxide. The quenching of the resulting alkyllithiums with ClCO2 Et furnishes stereoselectively syn- and anti-ethyl-2,3-dimethyl ester carboxylates (d.r.>94 %). Related esters bearing three adjacent stereo-controlled centers (stereotriads) have also been prepared. This method has been applied to the synthesis of the ant pheromone (±)-lasiol in 26 % overall yield (four steps) with d.r.=97:3 starting from commercially available cis-2,3-epoxybutane. PMID:27140953

  13. Chiral hybrid inorganic-organic materials: synthesis, characterization, and application in stereoselective organocatalytic cycloadditions.

    PubMed

    Puglisi, Alessandra; Benaglia, Maurizio; Annunziata, Rita; Chiroli, Valerio; Porta, Riccardo; Gervasini, Antonella

    2013-11-15

    The synthesis of chiral imidazolidinones on mesoporous silica nanoparticles, exploiting two different anchoring sites and two different linkers, is reported. Catalysts 1-4 were prepared starting from l-phenylalanine or l-tyrosine methyl esters and supporting the imidazolidinone onto silica by grafting protocols or azide-alkyne copper(I)-catalyzed cycloaddition. The four catalysts were fully characterized by solid-state NMR, N2 physisorption, SEM, and TGA in order to provide structural assessments, including an evaluation of surface areas, pore dimensions, and catalyst loading. They were used in organocatalyzed Diels-Alder cycloadditions between cyclopentadiene and different aldehydes, affording results comparable to those obtained with the nonsupported catalyst (up to 91% yield and 92% ee in the model reaction between cyclopentadiene and cinnamic aldehyde). The catalysts were recovered from the reaction mixture by simple filtration or centrifugation. The most active catalyst was recycled two times with some loss of catalytic efficiency and a small erosion of ee. PMID:24134403

  14. Stereoselective total synthesis of the glycosyl phosphatidylinositol (GPI) anchor of Trypanosoma brucei.

    PubMed

    Murakata, C; Ogawa, T

    1992-11-01

    The total synthesis of O-(O-[6-O-(2-aminoethylphosphono)-alpha-D-mannopyranosyl]-(1-->2)- O-alpha- D-mannopyranosyl-(1-->6)-O-[O-alpha-D-galactopyranosyl-(1-->6)-alpha-D- galactopyranosyl-(1-->3)]-O-alpha-D-mannopyranosyl-(1-->4)-2-amino-2-deo xy- alpha-D-glucopyranosyl)-(1-->6)-[1-O-(1,2-dimyristoyl-sn-glycero-3-phosp hono) - 1D-myo-inositol], the GPI anchor of Trypanosoma brucei was achieved for the first time. The core structure of the GPI molecule, the glycoheptaosyl part, was constructed in a highly stereocontrolled manner from O-[O-(2,4-di-O-benzyl-alpha-D-mannopyranosyl-(1-->4)-2-azido-3,6-di-O-be nzyl- 2-deoxy-D-glucopyranosyl]-(1-->6)-2,3,4,5-tetra-O-benzyl-1-O-(4- methoxybenzyl)-D-myo-inositol, O-(2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl)-(1-->6)-2,3,4-tri-O- benzyl-D-galactopyranosyl fluoride, 2-O-acetyl-3,4,6-tri-O-benzyl-alpha-D-mannopyranosyl chloride, and 6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-mannopyranosyl fluoride. The introduction of two phosphodiester functions was efficiently achieved using the H-phosphonate method. PMID:1473115

  15. Efficient synthesis and reactions of 1,2-dipyrrolylethynes

    PubMed Central

    Tanui, Hillary K.; Hao, Erhong; Ihachi, Moses I.; Fronczek, Frank R.; Smith, Kevin M.; Vicente, M. Graça H.

    2011-01-01

    Various dipyrroles possess important motifs for construction of pyrrole-containing pigments. A series of 1,2-dipyrrolylethynes (4a–d) has been efficiently synthesized using an improved one-pot double Sonagashira coupling from trimethylsilylethyne and various 2-iodopyrroles. The resulting 1,2-dipyrrolylethynes were further transformed into novel indolyl-, ethenyl- and carboranyl-dipyrroles (5–7) using the Larock indole synthesis, stereoselective catalytic hydrogenation, or B10H14. Indolyl-dipyrroles were found to selectively bind fluoride ions using one pyrrolic and the indolyl NHs, whereas the carboranyl- and ethenyl-dipyrroles are potentially valuable precursors for the synthesis of porphyrin isomers and expanded pigments. PMID:21822371

  16. Highly regio- and stereoselective synthesis of alpha-(N-alkyl-N-p-toluenesulfonyl)-beta-bromo-ketones via Ni(OAc)2-catalyzed aminobromination of chalcones.

    PubMed

    Sun, Hao; Zhi, San-Jun; Han, Jian-Lin; Li, Guigen; Pan, Yi

    2010-03-01

    The combinations of N-methyl-p-toluenesulfonamide/NBS and N-ethyl-p-toluenesulfonamide/NBS were found to be good nitrogen/halogen resources for the aminohalogenation of alpha,beta-unsaturated ketones in the presence of Ni(OAc)(2) as the catalyst for the synthesis of vicinal haloamino ketone derivatives. The introduction of N-alkyl groups to the nitrogen resources resulted in excellent regio- and stereoselectivity for both electron-donating and electron-withdrawing group-attached unsaturated ketone substrates. The structure of the resulting products has been unambiguously confirmed by X-ray crystal structure analysis. PMID:20331646

  17. Stereoselective and Regiodivergent Allylic Suzuki-Miyaura Cross-Coupling of 2-Ethoxydihydropyranyl Boronates: Synthesis and Confirmation of Absolute Stereochemistry of Diospongin B.

    PubMed

    Rybak, Taras; Hall, Dennis G

    2015-09-01

    Oxygen-containing heterocycles such as pyrans are a common substructure present in a variety of natural products and pharmaceutical drugs. Highly functionalized 4- and 6-aryl/heteroaryl dihydropyran derivatives are assembled by a highly stereoselective, ligand-controlled regiodivergent sp(3)-sp(2) Suzuki-Miyaura cross-coupling of a 2-ethoxy dihydropyranyl boronate derived from a catalytic enantioselective inverse-electron-demand oxa[4 + 2] cycloaddition. The scope and selectivity of this method were assessed along with an application to a concise total synthesis of the diarylheptanoid natural product diospongin B. PMID:26291472

  18. Highly Stereoselective Synthesis of Saccharin-Substituted β-Lactams via in Situ Generation of a Heterosubstituted Ketene and a Zwitterionic Intermediate as Potential Antibacterial Agents.

    PubMed

    Mortazavi, Zahra F A; Islami, Mohammad R; Khaleghi, Moj

    2015-06-19

    Highly stereoselective synthesis of saccharin derivatives containing functionalized 2-azetidinone moiety was achieved starting from saccharin as an available precursor. The approach to these valuable heterocyclic scaffolds involves a formal [2π + 2π] cycloaddition between Schiff bases and the saccharinylketene as a novel ketene which was generated in situ and an electrocyclic reaction of a zwitterionic intermediate. The identification of the ketene was confirmed by reaction with the stable free radical TEMPO (TO•). Also, the antimicrobial activities of some new substituted saccharin against nine standard bacteria, four bacteria which were isolated from clinical samples and one yeast, were evaluated. PMID:26029959

  19. Stereoselection in Intramolecular Diels-Alder Reactions of 2-Cyano-1-azadienes: Indolizidine and Quinolizidine Synthesis.

    PubMed

    Tay, Gidget C; Sizemore, Nicholas; Rychnovsky, Scott D

    2016-07-01

    Progress toward understanding the scope and diastereoselectivity of intramolecular Diels-Alder reactions using 2-cyano-1-azadienes is described herein. The resulting cyanoenamine products are underutilized intermediates in organic synthesis. Assembly of the Diels-Alder precursors was achieved using an improved imine condensation/oxidative cyanation protocol. By this method, several highly substituted indolizidine and quinolizidine architectures were constructed. Quantum mechanical DFT calculations at the B3LYP/6-31+G(d) level of theory were performed for these cyclizations and provide insights into the origins of the observed diastereoselectivities. PMID:27295460

  20. From glycals to aminosugars: a challenging test for new stereoselective aminohydroxylation and related methodologies.

    PubMed

    Mirabella, S; Cardona, F; Goti, A

    2016-06-21

    The introduction of amino functionalities in a regio- and stereoselective manner onto sugar scaffolds represents a great challenge in carbohydrate synthesis. The most relevant methods to access 1-, 2-, 3-amino or 1,2-diaminosugars starting from glycals and 2,3-hexenopyranosides derived from them are concisely reviewed. The main synthetic strategies for accessing this class of compounds are classified in intermolecular and intramolecular approaches and the key features of each class are discussed. This review highlights how carbohydrate derivatives always pose great challenges representing a benchmark for assessing the efficiency of stereoselective strategies, and aims to give the readers inspiration for the development of new procedures. PMID:27185584

  1. An efficient synthesis of loline alkaloids

    NASA Astrophysics Data System (ADS)

    Cakmak, Mesut; Mayer, Peter; Trauner, Dirk

    2011-07-01

    Loline (1) is a small alkaloid that, in spite of its simple-looking structure, has posed surprising challenges to synthetic chemists. It has been known for more than a century and has been the subject of extensive biological investigations, but only two total syntheses have been achieved to date. Here, we report an asymmetric total synthesis of loline that, with less then ten steps, is remarkably short. Our synthesis incorporates a Sharpless epoxidation, a Grubbs olefin metathesis and an unprecedented transannular aminobromination, which converts an eight-membered cyclic carbamate into a bromopyrrolizidine. The synthesis is marked by a high degree of chemo- and stereoselectivity and gives access to several members of the loline alkaloid family. It delivers sufficient material to support a programme aimed at studying the complex interactions between plants, fungi, insects and bacteria brokered by loline alkaloids.

  2. A non-canonical caleosin from Arabidopsis efficiently epoxidizes physiological unsaturated fatty acids with complete stereoselectivity.

    PubMed

    Blée, Elizabeth; Flenet, Martine; Boachon, Benoît; Fauconnier, Marie-Laure

    2012-10-01

    In plants, epoxygenated fatty acids (EFAs) are constituents of oil seeds as well as defence molecules and components of biopolymers (cutin, suberin). While the pleiotropic biological activities of mammalian EFAs have been well documented, there is a paucity of information on the physiological relevance of plant EFAs and their biosynthesis. Potential candidates for EFA formation are caleosin-type peroxygenases which catalyze the epoxidation of unsaturated fatty acids in the presence of hydroperoxides as co-oxidants. However, the caleosins characterized so far, which are mostly localized in seeds, are poor epoxidases. In sharp contrast, quantitative RT-PCR analysis revealed that PXG4, a class II caleosin gene, is expressed in roots, stems, leaves and flowers of Arabidopsis. Expressed in yeast, PXG4 encodes a calcium-dependent membrane-associated hemoprotein able to catalyze typical peroxygenase reactions. Moreover, we show here that purified recombinant PXG4 is an efficient fatty acid epoxygenase, catalyzing the oxidation of cis double bonds of unsaturated fatty acids. Physiological linoleic and linolenic acids proved to be the preferred substrates for PXG4; they are oxidized into the different positional isomers of the monoepoxides and into diepoxides. An important regioselectivity was observed; the C-12,13 double bond of these unsaturated fatty acids being the least favored unsaturation epoxidized by PXG4, linolenic acid preferentially yielded the 9,10-15,16-diepoxide. Remarkably, PXG4 catalyzes exclusively the formation of (R),(S)-epoxide enantiomers, which is the absolute stereochemistry of the epoxides found in planta. These findings pave the way for the study of the functional role of EFAs and caleosins in plants. PMID:22913587

  3. Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles.

    PubMed

    Kesornpun, Chatchai; Aree, Thammarat; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

    2016-03-14

    Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4-5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five- and six-membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having a unique hybrid isoxazoline-oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly-like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis. PMID:26914177

  4. Unstabilized azomethine ylides for the stereoselective synthesis of substituted piperidines, tropanes and azabicyclo[3.1.0] systems

    PubMed Central

    Ischay, Michael A.; Takase, Michael K.; Bergman, Robert G.; Ellman, Jonathan A.

    2013-01-01

    Acid treatment of densely substituted 2-silyl-1,2-dihydropyridines provides a new and convenient entry to reactive azomethine ylides that can (1) be protonated and reduced with high stereoselectivity to give piperidines, (2) participate in [3+2] dipolar cycloaddition to give tropanes, and (3) undergo a Nazarov-like 6-π electrocyclization that upon reduction give 2-azabicyclo[3.1.0] systems. PMID:23398467

  5. Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N-H Insertion Reaction of Metallocarbenes with β-Aminoketone Derivatives.

    PubMed

    Nicolle, Simon M; Lewis, William; Hayes, Christopher J; Moody, Christopher J

    2016-03-01

    A highly stereoselective route to functionalized pyrrolidines by the metal-catalyzed diverted N-H insertion of a range of diazocarbonyl compounds with β-aminoketone derivatives is described. A number of catalysts (rhodium(II) carboxylate dimers, copper(I) triflate, and an iron(III) porphyrin) are shown to promote the process under mild conditions to give a wide range of highly substituted proline derivatives. The reaction starts as a metallocarbene N-H insertion but is diverted by an intermolecular aldol reaction. PMID:26847664

  6. One-pot regio- and stereoselective synthesis of α'-methoxy-γ-pyrones: biological evaluation as mitochondrial respiratory complex inhibitors.

    PubMed

    Rosso, Helena; De Paolis, Michaël; Collin, Valérie C; Dey, Sriloy; Hecht, Sidney M; Prandi, Cristina; Richard, Vincent; Maddaluno, Jacques

    2011-11-18

    The one-pot construction of functionalized α'-methoxy-γ-pyrones is detailed. Starting from α,α'-dimethoxy-γ-pyrone, molecular diversity is attained by a regio- and stereoselective desymmetrization using allyllithium followed by vinylogous aldol reaction. Mechanistic considerations including density functional theory calculations and insightful experiments have been gathered to shed light on this complex multistep process. To illustrate the versatility of this methodology, some of the molecules prepared were evaluated for their ability to inhibit NADH-oxidase and NADH-ubiquinone oxidoreductase. In the process, a potent new inihibitor of NADH-oxidase activity (IC(50) 44 nM) was identified. PMID:22011074

  7. Chemical synthesis and enzymatic, stereoselective hydrolysis of a functionalized dihydropyrimidine for the synthesis of β-amino acids.

    PubMed

    Slomka, Christin; Zhong, Sabilla; Fellinger, Anna; Engel, Ulrike; Syldatk, Christoph; Bräse, Stefan; Rudat, Jens

    2015-12-01

    A novel substrate, 6-(4-nitrophenyl)dihydropyrimidine-2,4(1H,3H)-dione (pNO2PheDU), was chemically synthesized and analytically verified for the potential biocatalytic synthesis of enantiopure β-amino acids. The hydantoinase (EC 3.5.2.2) from Arthrobacter crystallopoietes DSM20117 was chosen to prove the enzymatic hydrolysis of this substrate, since previous investigations showed activities of this enzyme toward 6-monosubstituted dihydrouracils. Whole cell biotransformations with recombinant Escherichia coli expressing the hydantoinase showed degradation of pNO2PheDU. Additionally, the corresponding N-carbamoyl-β-amino acid (NCarbpNO2 βPhe) was chemically synthesized, an HPLC-method with chiral stationary phases for detection of this product was established and thus (S)-enantioselectivity toward pNO2PheDU has been shown. Consequently this novel substrate is a potential precursor for the enantiopure β-amino acid para-nitro-β-phenylalanine (pNO2 βPhe). PMID:26705241

  8. ent-Kaurane-Based Regio- and Stereoselective Inverse Electron Demand Hetero-Diels-Alder Reactions: Synthesis of Dihydropyran-Fused Diterpenoids†

    PubMed Central

    Ding, Chunyong; Wang, Lili; Chen, Haijun; Wild, Christopher; Ye, Na; Ding, Ye; Wang, Tianzhi; White, Mark A.; Shen, Qiang; Zhou, Jia

    2014-01-01

    A mild and concise approach for the construction of 3,4-dihydro-2H-pyran ring integrated into the A-ring of the natural product oridonin using an optimized inverse electron demand hetero-Diels-Alder (IED HDA) reaction is reported herein. A self-dimerization of the exocyclic enone installed in the A-ring through a homo-HDA reaction was identified to exclusively give a dimeric ent-kaurane diterpenoid with the spirochroman core. Moreover, the efficient cross-HDA cycloadditions of this enone with various vinyl ethers or vinyl sulfides, instead of its own homo-HDA dimerization, were achieved in regio- and stereoselective manners, thus providing the access to novel dihydropyran-fused diterpenoids as potential anticancer agents to overcome chemoresistance. PMID:25225052

  9. ent-Kaurane-based regio- and stereoselective inverse electron demand hetero-Diels-Alder reactions: synthesis of dihydropyran-fused diterpenoids.

    PubMed

    Ding, Chunyong; Wang, Lili; Chen, Haijun; Wild, Christopher; Ye, Na; Ding, Ye; Wang, Tianzhi; White, Mark A; Shen, Qiang; Zhou, Jia

    2014-11-14

    A mild and concise approach for the construction of a 3,4-dihydro-2H-pyran ring integrated into the A-ring of the natural product oridonin using an optimized inverse electron demand hetero-Diels-Alder (IED HDA) reaction is reported herein. A self-dimerization of the exocyclic enone installed in the A-ring through a homo-HDA reaction was identified to exclusively give a dimeric ent-kaurane diterpenoid with the spirochroman core. Moreover, efficient cross-HDA cycloadditions of this enone with various vinyl ethers or vinyl sulfides, instead of its own homo-HDA dimerization, were achieved in a regio- and stereoselective manner, thus providing access to novel dihydropyran-fused diterpenoids as potential anticancer agents to overcome chemoresistance. PMID:25225052

  10. Stereoselective synthesis of β-d-GlcNAc-(1→4)-D-Glc disaccharide starting from lactose.

    PubMed

    Guazzelli, Lorenzo; Catelani, Giorgio; D'Andrea, Felicia; Gragnani, Tiziana

    2014-03-31

    The stereoselective preparation of the β-d-GlcNAc-(1→4)-D-Glc disaccharide starting from known 4-O-[6-O-(1-methoxy-1-methylethyl)-3,4-O-isopropylidene-β-d-talopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose dimethyl acetal (2), in turn easily obtained from lactose, is reported. Key steps of this new procedure, that avoids the glycosylation reaction, are (a) a first epimerization at C-4' through an unusual procedure involving a completely stereospecific hydroboration-oxidation of the enol ether group of the hex-4-enopyranoside 4, obtained from 3 by base promoted acetone elimination, (b) an amination with inversion by S(N)2 reaction on an imidazylate intermediate, and, finally, (c) N-acetylation followed by complete deprotection. PMID:24614689

  11. Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups.

    PubMed

    Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold; Reissig, Hans-Ulrich

    2016-01-01

    Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID:27559374

  12. Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

    PubMed Central

    Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold

    2016-01-01

    Summary Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID:27559374

  13. Chemical synthesis of two series of nerve agent model compounds and their stereoselective interaction with human acetylcholinesterase and human butyrylcholinesterase

    PubMed Central

    Barakat, Nora H.; Zheng, Xueying; Gilley, Cynthia B.; MacDonald, Mary; Okolotowicz, Karl; Cashman, John R.; Vyas, Shubham; Beck, Jeremy M.; Hadad, Christopher M.; Zhang, Jun

    2009-01-01

    Both G- and V-type nerve agents possess a center of chirality about phosphorus. The Sp-enantiomers are generally more potent inhibitors than their Rp-counterparts toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To develop model compounds with defined centers of chirality that mimic the target nerve agent structures, we synthesized both the Sp and Rp stereoisomers of two series of G-type nerve agent model compounds in enantiomerically enriched form. The two series of model compounds contained identical substituents on the phosphorus as the G-type agents, except that thiomethyl (CH3-S-) and thiocholine ((CH3)3NCH2CH2-S-) groups were used to replace the traditional nerve agent leaving groups (i.e., fluoro for GB, GF, and GD; and cyano for GA). Inhibition kinetic studies of the thiomethyl- and thiocholine-substituted series of nerve agent model compounds revealed that the Sp enantiomers of both series of compounds showed greater inhibition potency toward AChE and BChE. The level of stereoselectivity, as indicated by the ratio of the bimolecular inhibition rate constants between Sp and Rp enantiomers, was greatest for the GF model compounds in both series. The thiocholine analogs were much more potent than the corresponding thiomethyl analogs. With the exception of the GA model compounds, both series showed greater potency against AChE than BChE. The stereoselectivity (i.e., Sp > Rp), enzyme selectivity, and dynamic range of inhibition potency contributed from these two series of compounds suggest that the combined application of these model compounds will provide useful research tools for understanding interactions of nerve agents with cholinesterase and other enzymes involved in nerve agent and organophosphate pharmacology. The potential of and limitations for using these model compounds in the development of biological therapeutics against nerve agent toxicity are also discussed. PMID:19715346

  14. Design and Stereoselective Preparation of a New Class of Chiral Olefin Metathesis Catalysts and Application to Enantioselective Synthesis of Quebrachamine: Catalyst Development Inspired by Natural Product Synthesis

    PubMed Central

    Sattely, Elizabeth S.; Meek, Simon J.; Malcolmson, Steven J.; Schrock, Richard R.; Hoveyda, Amir H.

    2010-01-01

    A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. A key catalytic ring-closing metathesis of an achiral triene is used to establish the all-carbon quaternary stereogenic center and the tetracyclic structure of the natural product; the catalytic transformation proceeds with reasonable efficiency through the use of existing achiral Ru or Mo catalysts. Ru- or Mo-based chiral olefin metathesis catalysts have proven to be inefficient and entirely nonselective in cases where the desired product is observed. In the present study, the synthesis route thus serves as a platform for the discovery of new olefin metathesis catalysts that allow for efficient completion of an enantioselective synthesis of quebrachamine. Accordingly, on the basis of mechanistic principles, stereogenic-at-Mo complexes bearing only monodentate ligands have been designed. The new catalysts provide significantly higher levels of activity than observed with the previously reported Ru- or Mo-based complexes. Enantiomerically enriched chiral alkylidenes are generated through diastereoselective reactions involving achiral Mo-based bispyrrolides and enantiomerically pure silyl-protected binaphthols. Such chiral catalysts initiate the key enantioselective ring-closing metathesis step in the total synthesis of quebrachamine efficiently (1 mol % loading, 22 °C, 1 h, >98% conversion, 84% yield) and with high selectivity (98:2 er, 96% ee). PMID:19113867

  15. Regio- and stereoselective synthesis of benzothiazolo-pyrimidinones via an NHC-catalyzed Mannich/lactamization domino reaction† †Electronic supplementary information (ESI) available. CCDC 1029497. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4cc08594a

    PubMed Central

    Ni, Qijian; Song, Xiaoxiao; Xiong, Jiawen; Raabe, Gerhard

    2015-01-01

    An NHC-catalyzed regio- and stereoselective Mannich/lactamization domino reaction of N-(benzothiazolyl)imines with α-chloroaldehydes has been developed. This new protocol provides a facile approach for the asymmetric synthesis of benzothiazolo-pyrimidinones and a pyrrolo[1,2-a]indolone in moderate to good yields (34–78%) and excellent stereoselectivities (87–99% ee, up to >20 : 1 d.r.). PMID:25476422

  16. Efficient N-Acyldopamine Synthesis.

    PubMed

    Matsumoto, Yotaro; Ito, Akihiro; Uesugi, Motonari; Kittaka, Atsushi

    2016-01-01

    N-Acyldopamines are endogenous analogs of capsaicin that exhibit cannabinoid-like activities and were identified from brain extracts. Among them, N-arachidonoyldopamine (AADA) and N-oleoyldopamine (ODA) were characterized as transient receptor potential vanilloid type V1 channel (TRPV1) ligands. Recently, it was shown that N-acyldopamines may possess diverse physiological roles in addition to their ligand activities. To study the multiple functions and action mechanisms of endogenous N-acyldopamines, a simple and efficient method of N-acyldopamine synthesis was investigated. The eighteen potentially endogenous N-acyldopamines and two deuterated ones, N-palmitoyl dopamine-d5 and N-stearoyl dopamine-d5, were efficiently synthesized without protective groups in CH2Cl2 under optimized conditions using propylphosphoric acid cyclic anhydride (PPACA) as a condensation agent. PMID:27373649

  17. Creation of a Broad-Range and Highly Stereoselective d-Amino Acid Dehydrogenase for the One-Step Synthesis of d-Amino Acids

    PubMed Central

    Vedha-Peters, Kavitha; Gunawardana, Manjula; Rozzell, J. David; Novick, Scott J.

    2008-01-01

    Using both rational and random mutagenesis, we have created the first known broad substrate range, nicotinamide cofactor dependent, and highly stereoselective d-amino acid dehydrogenase. This new enzyme is capable of producing d-amino acids via the reductive amination of the corresponding 2-keto acid with ammonia. This biocatalyst was the result of three rounds of mutagenesis and screening performed on the enzyme meso-diaminopimelate d-dehydrogenase. The first round targeted the active site of the wild-type enzyme and produced mutants that were no longer strictly dependent on the native substrate. The second and third rounds produced mutants that had an increased substrate range including straight- and branched-aliphatic amino acids and aromatic amino acids. The very high selectivity towards the d-enantiomer (95 to > 99% e.e) was shown to be preserved even after the addition of the five mutations found in the three rounds of mutagenesis and screening. This new enzyme could complement and improve upon current methods for d-amino acid synthesis. PMID:16910688

  18. Efficient total synthesis of novel bioactive microbial metabolites.

    PubMed

    Sunazuka, Toshiaki; Hirose, Tomoyasu; Omura, Satoshi

    2008-02-01

    neuroblastoma cell to further discover new AD medicines. Lactacystin has a novel gamma-lactam thioester structure and is also a selective and strong proteasome inhibitor. We have developed a concise approach to synthesize lactacystin designed to afford easy access to the original compound and a variety of analogs. Macrosphelides were isolated from Microsphaeropsis sp. FO-5050 from our screening of microbial metabolites that inhibit the adhesion of HL-60 cells to human umbilical vein endothelial cells (HUVEC). Macrosphelides are the first 16-membered macrotriolides. Macrosphelides prevent cell-cell adhesion by inhibiting the binding of sialyl Lewis X to E-selectin. We have accomplished the first efficient total synthesis of macrosphelides. Madindolines were isolated from Streptomyces nitrosporeus K93-0711 by our program to discover new interleukin 6 (IL-6) modulators. Madindolines are comprised of a 3a-hydroxyfuroindoline ring connected at nitrogen via a methylene bridge to a cyclopentene-1,3-dione ring. We have developed an efficient and practical total synthesis of madindolines. Madindoline A binds to gp130 selectively and inhibits IL-6 activity. Neoxaline was isolated from Aspergillus japonicus Fg-551. Neoxaline is a member of a novel class of biologically active indole alkaloids characterized by a unique indoline spiroaminal framework and binds to tubulin, which results in inhibition of tubulin polymerization. We have developed a concise stereoselective synthesis of the indoline spiroaminal framework of neoxaline. PMID:18217720

  19. Expanding the Scope of Primary Amine Catalysis: Stereoselective Synthesis of Indanedione-Fused 2,6-Disubstituted trans-Spirocyclohexanones.

    PubMed

    Madhusudhan Reddy, G; Ko, Chi-Ting; Hsieh, Kai-Hong; Lee, Chia-Jui; Das, Utpal; Lin, Wenwei

    2016-03-18

    A cinchona-alkaloid-derived chiral primary-amine-catalyzed enantioselective method for the synthesis of the thermodynamically less stable indanedione-fused 2,6-trans-disubstituted spirocyclohexanones is demonstrated. Both the enantiomeric forms of the trans isomer are obtained in excellent yields and enantioselectivities. Furthermore, one of the enantiopure trans-spiranes bearing an additional α-substitution on the cyclohexanone ring was then epimerized into its thermodynamically stable cis counterpart, with little loss of enantioselectivity to demonstrate the feasibility of such a transformation. Mechanistic investigations revealed two competing pathways, a concerted Diels-Alder reaction and a stepwise Michael addition, for the formation of corresponding products. PMID:26907160

  20. Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

    PubMed Central

    Hilgraf, Robert; Zimmermann, Nicole; Lehmann, Lutz; Tröger, Armin

    2012-01-01

    Summary Following our earlier approach to the synthesis of dihydronepetalactones, all eight stereoisomers of trans-fused iridomyrmecins were synthesized starting from the enantiomers of limonene. Combined gas chromatography and mass spectrometry including enantioselective gas chromatography revealed that volatiles released by the endohyperparasitoid wasp Alloxysta victrix contain (4S,4aR,7S,7aR)-iridomyrmecin of 95–97% ee and stereochemically pure (4S,4aS,7R,7aS)-iridomyrmecin as a minor component. PMID:23019456

  1. Direct Stereocontrolled Synthesis of 3-Amino-3-deoxy-β-Mannopyranosides: Importance of the Nitrogen Protecting Group on Stereoselectivity

    PubMed Central

    Crich, David; Xu, Huadong

    2008-01-01

    The highly stereocontrolled synthesis of the 3-amino-3-deoxy-β-mannopyranosides is achieved by means of thioglycoside donors protected with a 4,6-O-benzylidene or alkylidene acetal and a benzylidene imine group. Among the various nitrogen protecting groups investigated only the Schiff’s base was found to give high β-selectivity. N-Phthalimido and N-acetamido protected donors were found to be highly α-selective, whereas 3-azido-3-deoxy glycosyl donors gave intermediate selectivity. The reasons for the protecting group dependency are discussed in terms of the change in the O2-C2-C3-N3 torsional interaction on conversion of the covalent glycosyl triflates to the transient oxacarbenium ions. PMID:17567072

  2. Regio- and stereoselective biomimetic synthesis of oligostilbenoid dimers from resveratrol analogues: influence of the solvent, oxidant, and substitution.

    PubMed

    Velu, Saraswati S; Buniyamin, Irmaizatussyehdany; Ching, Lee Kiew; Feroz, Fareeda; Noorbatcha, Ibrahim; Gee, Lim Chuan; Awang, Khalijah; Wahab, Ibtisam Abd; Weber, Jean-Frédéric Faizal

    2008-01-01

    Oligostilbenoids are polyphenols that are widely distributed in nature with multifaceted biological activities. To achieve biomimetic synthesis of unnatural derivatives, we subjected three resveratrol analogues to oligomerization by means of one-electron oxidants. Upon varying the metal oxidant (AgOAc, CuBr(2), FeCl(3)6 H(2)O, FeCl(3)6 H(2)O/NaI, PbO(2), VOF(3)), the solvent (over the whole range of polarities), and the oxygenated substitution pattern of the starting material, stilbenoid oligomers with totally different carbon skeletons were obtained. Here we propose to explain the determinism of the type of skeleton produced with the aid of hard and soft acid/base concepts in conjunction with the solvating properties of the solvents and the preferred alignment by the effect of pi stacking. PMID:19003831

  3. Redesigning Aldolase Stereoselectivity by Homologous Grafting

    PubMed Central

    Henßen, Birgit; Metz, Alexander; Gohlke, Holger; Pietruszka, Jörg

    2016-01-01

    The 2-deoxy-d-ribose-5-phosphate aldolase (DERA) offers access to highly desirable building blocks for organic synthesis by catalyzing a stereoselective C-C bond formation between acetaldehyde and certain electrophilic aldehydes. DERA´s potential is particularly highlighted by the ability to catalyze sequential, highly enantioselective aldol reactions. However, its synthetic use is limited by the absence of an enantiocomplementary enzyme. Here, we introduce the concept of homologous grafting to identify stereoselectivity-determining amino acid positions in DERA. We identified such positions by structural analysis of the homologous aldolases 2-keto-3-deoxy-6-phosphogluconate aldolase (KDPG) and the enantiocomplementary enzyme 2-keto-3-deoxy-6-phosphogalactonate aldolase (KDPGal). Mutation of these positions led to a slightly inversed enantiopreference of both aldolases to the same extent. By transferring these sequence motifs onto DERA we achieved the intended change in enantioselectivity. PMID:27327271

  4. Redesigning Aldolase Stereoselectivity by Homologous Grafting.

    PubMed

    Bisterfeld, Carolin; Classen, Thomas; Küberl, Irene; Henßen, Birgit; Metz, Alexander; Gohlke, Holger; Pietruszka, Jörg

    2016-01-01

    The 2-deoxy-d-ribose-5-phosphate aldolase (DERA) offers access to highly desirable building blocks for organic synthesis by catalyzing a stereoselective C-C bond formation between acetaldehyde and certain electrophilic aldehydes. DERA´s potential is particularly highlighted by the ability to catalyze sequential, highly enantioselective aldol reactions. However, its synthetic use is limited by the absence of an enantiocomplementary enzyme. Here, we introduce the concept of homologous grafting to identify stereoselectivity-determining amino acid positions in DERA. We identified such positions by structural analysis of the homologous aldolases 2-keto-3-deoxy-6-phosphogluconate aldolase (KDPG) and the enantiocomplementary enzyme 2-keto-3-deoxy-6-phosphogalactonate aldolase (KDPGal). Mutation of these positions led to a slightly inversed enantiopreference of both aldolases to the same extent. By transferring these sequence motifs onto DERA we achieved the intended change in enantioselectivity. PMID:27327271

  5. Organocatalytic Synthesis of Higher‐Carbon Sugars: Efficient Protocol for the Synthesis of Natural Sedoheptulose and d‐Glycero‐l‐galacto‐oct‐2‐ulose†

    PubMed Central

    Popik, Oskar; Pasternak‐Suder, Monika; Baś, Sebastian

    2015-01-01

    Abstract Herein we report a short and efficient protocol for the synthesis of naturally occurring higher‐carbon sugars—sedoheptulose (d‐altro‐hept‐2‐ulose) and d‐glycero‐l‐galacto‐oct‐2‐ulose—from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn‐selective aldol reaction of DHA with d‐erythrose and d‐xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn‐selective carbon–carbon‐bond‐forming aldol reactions promoted by primary‐based organocatalysts. For example, this methodology provided useful access to d‐glycero‐d‐galacto‐oct‐2‐ulose and 1‐deoxy‐d‐glycero‐d‐galacto‐oct‐2‐ulose from d‐arabinose in high yield (85 and 74 %, respectively) and high stereoselectivity (99:1). PMID:27308197

  6. Stereoselective synthesis of glycobiosyl phosphatidylinositol, a part structure of the glycosyl-phosphatidylinositol (GPI) anchor of Trypanosoma brucei.

    PubMed

    Murakata, C; Ogawa, T

    1992-10-01

    O-alpha-D-Mannopyranosyl-(1-->4)-O-2-amino-2-deoxy-alpha-D-glucopyranosy l- (1-->6)-1D-myo-inositol 1-(1,2-di-O-myristoyl-sn-glycer-3-yl hydrogen phosphate), a part structure of the glycosyl-phosphatidylinositol (GPI) anchor of Trypanosoma brucei, was synthesised efficiently by the phosphonate approach. The glycobiosylinositol core was prepared in a stereocontrolled manner from 1D-2,3,4,5-tetra-O-benzyl-1-O-(4-methoxybenzyl)-myo-inositol, tert-butyldimethylsilyl 2-azido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside, and methyl 3,6-di-O-acetyl-2,6-di-O-benzyl-2-thio-alpha-D-mannopyranoside. PMID:1468082

  7. Assembly of a Complex Branched Oligosaccharide by Combining Fluorous-Supported Synthesis and Stereoselective Glycosylations using Anomeric Sulfonium Ions.

    PubMed

    Huang, Wei; Gao, Qi; Boons, Geert-Jan

    2015-09-01

    There is an urgent need to develop reliable strategies for the rapid assembly of complex oligosaccharides. This paper presents a set of strategically selected orthogonal protecting groups, glycosyl donors modified by a (S)-phenylthiomethylbenzyl ether at C-2, and a glycosyl acceptor containing a fluorous tag, which makes it possible to rapidly prepare complex branched oligosaccharides of biological importance. The C-2 auxiliary controlled the 1,2-cis anomeric selectivity of the various galactosylations. The orthogonal protecting groups, 2-naphthylmethyl ether (Nap) and levulinic ester (Lev), made it possible to generate glycosyl acceptors and allowed the installation of a crowded branching point. After the glycosylations, the chiral auxiliary could be removed using acidic conditions, which was compatible with the presence of the orthogonal protecting groups Lev and Nap, thereby allowing the efficient installation of 1,2-linked glycosides. The light fluorous tag made it possible to purify the compounds by a simple filtration method using silica gel modified by fluorocarbons. The set of building blocks was successfully employed for the preparation of the carbohydrate moiety of the GPI anchor of Trypanosoma brucei, which is a parasite that causes sleeping sickness in humans and similar diseases in domestic animals. PMID:26250358

  8. Exploring stereoselectivity of 3-indolyl cyclopent[b]indoles: a parallel synthesis and anti-EGFR study on human cancer cells.

    PubMed

    Fan, Dacheng; Sun, Weizhi; Qiu, Peiju; Wu, Zhiyong; Li, Yantuan; Wan, Shengbiao; Jiang, Tao; Zhang, Lijuan

    2014-03-01

    We synthesized a series of novel 3-indolyl cyclopent[b]indoles by trifluoroacetic acid mediated cyclodimerizations. The reaction showed high stereoselectivity and moderate to good yields. The influencing factors for stereoselectivity were systematically analyzed and a stepwise reaction mechanism was proposed. The cell viability tests in two colon and two lung cancer cell lines indicated the 1-benzyl-2-phenyl-group in 3-indolyl cyclopent[b]indoles was critical for the observed lower IC₅₀s in these compounds. Western blot analysis demonstrated that the compound inhibited the expression and phosphorylation of EGFR through altered HSP90 expression. Further cell cycle and cell cycle check point protein analyses showed expected anti-cellular proliferation and cell cycle arresting properties associated with suppressed EGFR expression and phosphorylation. These data revealed a novel molecular mechanism explaining the observed cytotoxicities for these compounds. PMID:24518873

  9. A highly efficient preparative method of alpha-ylidene-beta-diketones via Au(III)-catalyzed acyl migration of propargylic esters.

    PubMed

    Wang, Shaozhong; Zhang, Liming

    2006-07-01

    A highly efficient synthesis of alpha-alkylidene or benzylidene-beta-diketones from readily available propargylic esters has been developed. The proposed key transformation is a novel intramolecular acyl migration to nucleophilic AuIII-C(sp2) bonds. Noteworthy features of this method are its efficiency and stereoselectivity. The yields of this reaction were mostly close to quantitative, and high to excellent stereoselectivities were observed in the cases of dienyl beta-diketones. PMID:16802803

  10. Tactical Synthesis Of Efficient Global Search Algorithms

    NASA Technical Reports Server (NTRS)

    Nedunuri, Srinivas; Smith, Douglas R.; Cook, William R.

    2009-01-01

    Algorithm synthesis transforms a formal specification into an efficient algorithm to solve a problem. Algorithm synthesis in Specware combines the formal specification of a problem with a high-level algorithm strategy. To derive an efficient algorithm, a developer must define operators that refine the algorithm by combining the generic operators in the algorithm with the details of the problem specification. This derivation requires skill and a deep understanding of the problem and the algorithmic strategy. In this paper we introduce two tactics to ease this process. The tactics serve a similar purpose to tactics used for determining indefinite integrals in calculus, that is suggesting possible ways to attack the problem.

  11. One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular SN2 reaction.

    PubMed

    Xiong, Yiwen; Qian, Ping; Cao, Chenhui; Mei, Haibo; Han, Jianlin; Li, Guigen; Pan, Yi

    2014-01-01

    We report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) . PMID:25161740

  12. One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular SN2 reaction

    PubMed Central

    Xiong, Yiwen; Qian, Ping; Cao, Chenhui; Mei, Haibo; Li, Guigen

    2014-01-01

    Summary We report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) . PMID:25161740

  13. Palladium(II)-Catalyzed Cross-Dehydrogenative Coupling (CDC) of N-Phthaloyl Dehydroalanine Esters with Simple Arenes: Stereoselective Synthesis of Z-Dehydrophenylalanine Derivatives.

    PubMed

    Bartoccini, Francesca; Cannas, Diego Maria; Fini, Francesco; Piersanti, Giovanni

    2016-06-01

    Pd(II)-catalyzed cross-dehydrogenative coupling (CDC) of methyl N-phthaloyl dehydroalanine esters with simple aromatic hydrocarbons is reported. The reaction, which involves the cleavage of two sp(2) C-H bonds followed by C-C bond formation, stereoselectively generates highly valuable Z-dehydrophenylalanine skeletons in a practical, versatile, and atom economical manner. In addition, a perfluorinated product was expediently converted into important nonproteinogenic amino acid building blocks through copper-catalyzed conjugate additions of boron, silicon, and hydride moieties. PMID:27206072

  14. Aryl(trifluoroethyl)iodonium Triflimide and Nitrile Solvent Systems: A Combination for the Stereoselective Synthesis of Armed 1,2-trans-β-Glycosides at Noncryogenic Temperatures.

    PubMed

    Chu, An-Hsiang Adam; Minciunescu, Andrei; Bennett, Clay S

    2015-12-18

    Armed thioglycosides can be activated with aryl(trifluoroethyl)iodonium triflimide in 2:1 CH2Cl2/pivalonitrile or a solvent combination of CH2Cl2, acetonitrile, isobutyronitrile, and pivalonitrile (6:1:1:1) at 0 °C for glycosylation reactions that proceed in good yield and moderate to excellent selectivity (up to 25:1 β/α). Comparison to other common glycosylation promoters reveals that both the mixed solvent and the iodonium salt promoter are required for stereoselectivity. PMID:26634960

  15. Efficient Biocatalytic Synthesis of Chiral Chemicals.

    PubMed

    Zhang, Zhi-Jun; Pan, Jiang; Ma, Bao-Di; Xu, Jian-He

    2016-01-01

    Chiral chemicals are a group of important chiral synthons for the synthesis of a series of pharmaceuticals, agrochemicals, and fine chemicals. In past decades, a number of biocatalytic approaches have been developed for the green and effective synthesis of various chiral chemicals. However, the practical application of these biocatalytic processes is still hindered by the lack of highly efficient and robust biocatalysts, which usually results in the low volumetric productivity and high cost of the bioprocesses. Further step forward of biocatalysis in industrial application strongly requires the development of versatile and highly efficient biocatalysts, aiming to increase the process efficiency and facilitate the downstream processing. Recently, the fast growth of genome sequences in the database in post-genomic era offers great opportunities for accessing numerous biocatalysts with practical application potential, and the so-called genome mining approach provides time-effective and highly specific strategy for the fast identification of target enzymes with desired properties and outperforms the traditional screening of soil samples for microbial enzyme producers of interest. A number of biocatalytic processes with industrial application potential were developed thereafter. Further development of protein engineering strategies, process optimization, and cooperative work between biologists, organic chemists, and engineers is expected to make biocatalysis technology the first choice approach for the eco-friendly, highly efficient, and cost-effective synthesis of chiral chemicals in the near future. PMID:25537446

  16. Unexpected isocyanide-based three-component bicyclizations for stereoselective synthesis of densely functionalized pyrano[3,4-c]pyrroles

    PubMed Central

    Gao, Qian; Hao, Wen-Juan; Liu, Feng; Wang, Shu-Liang

    2015-01-01

    A novel three-component bicyclization strategy for efficient synthesis of densely functionalized pyrano[3,4-c]pyrroles has been established from readily accessible 3-aroylacrylic acids, dialkyl acetylenedicarboxylates and isocyanides. The reaction pathway involves Huisgen 1,3-dipole formation, Passerini-type reaction, Mumm rearrangement and oxo-Diels–Alder reaction sequence, resulting in continuous multiple bond-forming events including C–N, C–O and C–H bonds to rapidly build up molecular complexity. PMID:26576646

  17. Approximation concepts for efficient structural synthesis

    NASA Technical Reports Server (NTRS)

    Schmit, L. A., Jr.; Miura, H.

    1976-01-01

    It is shown that efficient structural synthesis capabilities can be created by using approximation concepts to mesh finite element structural analysis methods with nonlinear mathematical programming techniques. The history of the application of mathematical programming techniques to structural design optimization problems is reviewed. Several rather general approximation concepts are described along with the technical foundations of the ACCESS 1 computer program, which implements several approximation concepts. A substantial collection of structural design problems involving truss and idealized wing structures is presented. It is concluded that since the basic ideas employed in creating the ACCESS 1 program are rather general, its successful development supports the contention that the introduction of approximation concepts will lead to the emergence of a new generation of practical and efficient, large scale, structural synthesis capabilities in which finite element analysis methods and mathematical programming algorithms will play a central role.

  18. Diastereoselective Total Synthesis of (-)-Galiellalactone.

    PubMed

    Kim, Taewoo; Han, Young Taek; An, Hongchan; Kim, Kyeojin; Lee, Jeeyeon; Suh, Young-Ger

    2015-12-18

    An enantioselective total synthesis of (-)-galiellalactone has been accomplished. The key features of the synthesis involve the highly stereoselective construction of the cis-trisubstituted cyclopentane intermediate by a Pd(0)-catalyzed cyclization, the stereospecific introduction of an angular hydroxyl group by Riley oxidation, and the efficient construction of the tricyclic system of (-)-galiellalactone via a combination of diastereoselective Hosomi-Sakurai crotylation and ring-closing metathesis (RCM). PMID:26544529

  19. [Saccharomyces cerevisiae B5 efficiently and stereoselectively reduces 2'-chloroacetophenone to R-2'-chloro-1-phenylethanol in the presence of 5% ethanol].

    PubMed

    Ou, Zhi-Min; Wu, Jian-Ping; Yang, Li-Rong; Cen, Pei-Lin; Liu, Lin; Qi, Nan

    2003-03-01

    (R)-chlorprenaline, a selective activator of beta2 receptor and an effective drug for bronchitis and asthma, is industrially prepared from (R)-2'-chloro-1-phenyl-ethanol. In this communication, we describe (1) the identification of Saccharomyces cerevisiae B5 as an effective host for stereoselective reduction of 2'-chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol; (2) the presence of ethanol enhances the conversion; and (3) the biochemical factors that effect the yield of the product. Among the four yeast strains capable of reduction 2'-chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol we screened, Saccharomyces cerevisiae B5 showed the highest activity and stereoselectivity, and was used for the subsequent study. The effect of the presence of methanol, ethanol, 2-propanol, 1-butanol, glucose, glycerol and lactic acid was first investigated, as it was previously reported that they increased the yield and stereoselectivity of the reaction. The addition of the co-substrate methanol, ethanol, 2-propanol, 1-butanol, glucose and glycerol favored the formation of the 2'-chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol. Lactic acid inhibited the enzyme activity. Ethanol is the best co-substrate among the seven co-substrates and under the optimum concentration of 5% , the yield of (R)-2'-chloro-1-phenyl-ethanol was increased from 17% to 74%. The oxidation of ethanol regenerates NADH required for the reduction. The effects of the reaction time, pH, cell concentration, substrate concentration and temperature on the reduction were investigated next. The enantiometric excess of (R)-2'-chloro-1-phenyl-ethanol reached 100% under the optimal condition: pH8.0, 25 degrees C and 5% ethanol. The product yield went up with the increasing Saccharomyces cerevisiae B5 concentration and reached 100% when the cell dry weight was 10.75 mg/mL and 2'-chloroacetophenone was 6.47 mmol/L. The yield of (R)-2'-chloro-1-phenyl-ethanol decreased sharply with the increase of substrate

  20. Stereoselective Reduction of Imines with Trichlorosilane Using Solid-Supported Chiral Picolinamides.

    PubMed

    Fernandes, Sílvia D; Porta, Riccardo; Barrulas, Pedro C; Puglisi, Alessandra; Burke, Anthony J; Benaglia, Maurizio

    2016-01-01

    The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials revealed that polystyrene gave better results than silica in terms of stereoselectivity. The applicability of the solid-supported catalyst of choice to the reduction of different imines was also demonstrated. Additionally, for the first time, a catalytic reactor containing a polymer-immobilized chiral picolinamide has been employed for the stereoselective reduction of imines with trichlorosilane under continuous flow conditions. PMID:27608000

  1. Regio- and stereoselective synthesis of pregnane-fused isoxazolines by nitril-oxide/alkene 1,3-dipolar cycloaddition and an evaluation of their cell-growth inhibitory effect in vitro

    NASA Astrophysics Data System (ADS)

    Mótyán, Gergő; Baji, Ádám; Zupkó, István; Frank, Éva

    2016-04-01

    Efficient syntheses of some pregnane-fused isoxazolines from 16-dehydropregnenolone acetate with different arylnitrile oxides were carried out by 1,3-dipolar cycloadditions. The intermolecular ring-closures occurred in a highly regio- and stereoselective manner permitting the formation of a single 16α,17α-condensed diastereomer in which the O terminus of the nitrile oxide dipole is attached to C-17 of the sterane core. The conversions were found to be affected significantly by the electronic character of the substituents on the aromatic moiety of the 1,3-dipoles. Deacetylation of the primary products resulted in the corresponding 3β-OH analogs. All of the synthesized compounds were subjected to in vitro pharmacological studies for the determination of their antiproliferative effects on four breast cancer cell lines (MCF7, T47D, MDA-MB-231 and MDA-MB-361).

  2. Azomethine Ylides from Nitrones: Using Catalytic nBuLi for the Totally Stereoselective Synthesis of trans-2-Alkyl-3-oxazolines.

    PubMed

    Juste-Navarro, Veronica; Delso, Ignacio; Tejero, Tomás; Merino, Pedro

    2016-08-01

    The cycloaddition of azomethine ylide N-oxides (nitrone ylides) with aldehydes provides 3-oxazolines in a completely stereoselective manner in the presence of a catalytic amount of n-butyllithium. The process involves an initial nucleophilic attack on the aldehyde, followed by intramolecular oxygen addition to the nitrone moiety and lithium-assisted elimination of water, regenerating the catalytic species. Various Li-based catalytic systems are possible and the in situ generated water is required for continuing the catalytic cycle. The best results are observed with 20 mol % of n-butyllithium, whereas the use of stoichiometric amounts inhibit the rate of catalysis. Experimental, spectroscopic, and computational mechanistic studies have provided evidence of lithium-ion catalysis and rationalized several competing catalytic pathways. PMID:27258625

  3. Stereoselective synthesis of 11-phenylundeca-5Z,9Z-dienoic acid and investigation of its human topoisomerase I and IIα inhibitory activity.

    PubMed

    D'yakonov, Vladimir A; Dzhemileva, Lilya U; Makarov, Aleksey A; Mulukova, Alfiya R; Baev, Dmitry S; Khusnutdinova, Elza K; Tolstikova, Tatiana G; Dzhemilev, Usein M

    2015-06-01

    (5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of Cp2TiCl2 catalyst giving 2,5-dialkylidenemagnesacyclopentane in 86% yield. The acid hydrolysis of the product and the Jones oxidation of the resulting 2-{[(5Z,9Z)-11-phenylundeca-5,9-dien-1-yl]oxy}tetrahydro-2Н-pyran afforded (5Z,9Z)-11-phenylundeca-5,9-dienoic acid in an overall yield of 75%. A high inhibitory activity of the synthesized acid with respect to human topoisomerase I (hTop1) and II (hTop2α) was determined. PMID:25913198

  4. Macrocyclic polyenynes: a stereoselective route to vinyl-ether-containing skipped diene systems.

    PubMed

    Ronson, Thomas O; Voelkel, Martin H H; Taylor, Richard J K; Fairlamb, Ian J S

    2015-05-11

    The stereoselective synthesis of a challenging macrocyclic polyene scaffold, containing a sensitive vinyl ether motif, has been accomplished using O,C-dilithiation/selective C-alkylation, Pd-catalysed etherification and Wittig reactions as key steps. An end-game macrocyclisation strategy employed a regio- and stereoselective Stille cross-coupling using Pd(Br)(N-Succ)(AsPh3)2 (AsCat) as the precatalyst. PMID:25891970

  5. Efficient synthesis of benzamide riboside, a potential anticancer agent.

    PubMed

    Bonnac, Laurent F; Gao, Guang-Yao; Chen, Liqiang; Patterson, Steven E; Jayaram, Hiremagalur N; Pankiewicz, Krzysztof W

    2007-01-01

    An efficient five step synthesis of benzamide riboside (BR) amenable for a large scale synthesis has been developed. It allows for extensive pre-clinical studies of BR as a potential anticancer agent. PMID:18066762

  6. Efficient Synthesis of Fluorescent Squaraine Rotaxane Dendrimers

    PubMed Central

    Xiao, Shuzhang; Fu, Na; Peckham, Kaitlin; Smith, Bradley D.

    2009-01-01

    A squaraine rotaxane scaffold with four alkynes groups is readily converted into a range of dendritic architectures using high yielding copper catalyzed alkyne azide cycloaddition (CuAAC) chemistry. A convergent synthesis approach is more efficient than a divergent pathway. Dendritic squaraine rotaxanes with peripheral amine groups can be further functionalized to produce multivalent deep-red fluorescent derivatives that exhibit high brightness and outstanding chemical stability in biological solution. The surface groups on these functionalized fluorescent dendrimers include guanidinium, mannose, and phosphatidylcholine. PMID:19957971

  7. Stereoselective aminoacylation of RNA

    NASA Technical Reports Server (NTRS)

    Usher, D. A.; Needels, M. C.; Brenner, T.

    1986-01-01

    Prebiotic chemistry is faced with a major problem: how could a controlled and selective reaction occur, when there is present in the same solution a large number of alternative possible coreactants? This problem is solved in the modern cell by the presence of enzymes, which are not only highly efficient and controllable catalysts, but which also can impose on their substrates a precise structural requirement. However, enzymes are the result of billions of years of evolution, and we cannot invoke them as prebiotic catalysts. One approach to solving this problem in the prebiotic context is to make use of template-directed reactions. These reactions increase the number of structural requirements that must be simultaneously present in a molecule for it to be able to react, and thereby increase the selectivity of the reaction. They also can give a large increase in the rate of a reaction, if the template constrains two potential coreactants to lie close together. A third benefit is that information that is present in the template molecule can be passed on to the product molecules. If the earliest organisms were based on proteins and nucleic acids, then the investigation of peptide synthesis on an oligonucleotide template is highly relevant to the study of the origin of life.

  8. Stereoselective synthesis of biphenolate/binaphtolate titanate and zirconate alkoxide species: structural characterization and use in the controlled ROP of lactide.

    PubMed

    Azor, Laurine; Bailly, Corinne; Brelot, Lydia; Henry, Marc; Mobian, Pierre; Dagorne, Samuel

    2012-10-15

    Well-defined biphenol/binaphtolate group 4 alkoxide salt species [(Ph-Biphen-O)(2)M(O(i)Pr)]Li(THF) (2a, M = Ti; 4a, M = Zr) and [(Ph-binapht-O)(2)M(O(i)Pr)]Li(THF) (2b, M = Ti; 4b, M = Zr) were found to be readily accessible in good yields via alcohol elimination routes and/or substitution reactions from the corresponding pro-ligands Ph-Biphen-OH (1a) and rac-Ph-Binapht-OH (1b). As established via X-ray crystallographic analysis, the molecular structures of the Ti derivatives 2a and 2b consist of Li(+) salts of anionic Ti-O(i)Pr moieties in which the Ti center adopts a distorted tbp geometry and is effectively chelated by two biphenolate/binaphtolate units. Remarkably, the solution and solid state data for salt species 2a,b agree with the sole presence of one diastereomer (with a (Δ, aS, aS)/(Λ, aR, aR) configuration), thus indicating that formation of the Ti and Zr alkoxide complexes 2a,b/4a,b proceeds stereoselectively. In contrast, the neutral biphenolate/binaphtolate Zr complexes (Ph-biphen-O)(2)Zr(THF)(2) (3a) and (Ph-binapht-O)(2)Zr(THF)(2) (3b) were both isolated and X-ray characterized as stereomers in a heterochiral configuration (Δ, aR, aS)/(Λ, aS, aR). The Ti and Zr alkoxide anionic chelates were found to initiate the ROP of rac-lactide in a controlled manner for production of narrowly disperse and ester-end group PLA, as deduced from SEC, kinetic, and MALDI-TOF data. The Zr-O(i)Pr derivatives 4a,b exhibit superior performance to their Ti counterparts (whether regarding activity, polymerization control, or stereoselectivity) to produce narrowly disperse and heterotactically enriched PLA (P(r) = 0.67, PDI < 1.15). The significantly decreased Lewis acidity of the Zr metal center in anions 4a,b (versus neutral analogues) due to the anionic charge and a likely substantial electronic π donation of the four Zr-O(ArO) oxygens to the Zr metal center may rationalize the moderate polymerization activity. Control experiments suggest that the nature of the

  9. Synthesis of cyclic sulfones by ring-closing metathesis.

    PubMed

    Yao, Qingwei

    2002-02-01

    A general and highly efficient synthesis of cyclic sulfones based on ring-closing metathesis has been developed. The synthetic utility of the resulting cyclic sulfones was demonstrated by their participation in stereoselective Diels-Alder reactions and transformation to cyclic dienes by the Ramberg-Bäcklund reaction. PMID:11820896

  10. Biotransformation: a green and efficient way of antioxidant synthesis.

    PubMed

    Zafar, Salman; Ahmed, Rida; Khan, Rasool

    2016-09-01

    Antioxidant compounds play a vital role in human physiology. They prevent the oxidation of biomolecules by scavenging free radicals produced during physiochemical processes and/or as a result of several pathological states. A balance between the reactive oxygen species (free radicals) and antioxidants is essential for proper physiological conditions. Excessive free radicals cause oxidative stress which can lead to several human diseases. Therefore, synthesis of the effective antioxidants is crucial in managing the oxidative stress. Biotransformation has evolved as an effective technique for the production of structurally diverse molecules with a wide range of biological activities. This methodology surpasses the conventional chemical synthesis due to the fact that enzymes, being specific in nature, catalyze reactions affording products with excellent regio- and stereoselectivities. Structural transformation of various classes of compounds such as alkaloids, steroids, flavonoids, and terpenes has been carried out through this technique. Several bioactive molecules, especially those having antioxidant potential have also been synthesized by using different biotransformation techniques and enzymes. Hydroxylated, glycosylated, and acylated derivatives of phenols, flavonoids, cinnamates, and other molecules have proven abilities as potential antioxidants. A critical review of the biotransformation of these compounds into potent antioxidant metabolites is presented here. PMID:27383446

  11. Stereoselective Synthesis and Modelling-Driven Optimisation of Carane-Based Aminodiols and 1,3-Oxazines as Catalysts for the Enantioselective Addition of Diethylzinc to Benzaldehyde.

    PubMed

    Szakonyi, Zsolt; Csőr, Árpád; Csámpai, Antal; Fülöp, Ferenc

    2016-05-17

    The reductive amination of (-)-2-carene-3-aldehyde, prepared in two steps from (-)-perillaldehyde, furnished 2-carene-based allylamines. tert-Butyloxycarbonyl (Boc) or carbobenzyloxy (Cbz) protection of the resulting amines, followed by stereoselective dihydroxylation in highly stereospecific reactions with OsO4 and subsequent deprotection, resulted in N-benzylaminodiols, which were transformed to primary and tertiary aminodiols. The reactions of the N-benzyl- and N-(1-phenylethyl)-substituted derivatives with formaldehyde led to highly regioselective ring closure, resulting in carane-fused 1,3-oxazines. The aminodiols and their 1,3-oxazine derivatives were applied as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. The best (R) enantioselectivity was observed in the case of the N-((R)-1-phenylethyl)-substituted aminodiol, whereas the opposite chiral direction was preferred when the 1,3-oxazines were applied. Through the use of molecular modelling at an ab initio level, this phenomenon was interpreted in terms of competing reaction pathways. Molecular modelling at the RHF/LANL2DZ level of theory was successfully applied for a mechanism-based interpretation of the stereochemical outcome of the reactions leading to the development of further 1,3-oxazine-based ligands, which display excellent (S) enantioselectivity (95 and 98 % ee) in the examined transformation. PMID:27072603

  12. endo/exo stereoselectivity in Diels-Alder reactions of α,β-dialkylated conjugated enals to cyclic 1,3-dienes: intermediates in the synthesis of (-)-β-santalol and its analogs.

    PubMed

    Chapuis, Christian; Skuy, David; de Saint Laumer, Jean-Yves; Brauchli, Robert

    2014-10-01

    Highly exo-selective [4+2] cycloadditions of cyclopenta-1,3-diene 2a to α,β-dialkyl conjugated enals 5 are compared with the analogous endo-favored Diels-Alder reaction of cyclohexa-1,3-diene 7. The exo-stereoselectivity is lower in the homologous case of methylcyclopenta-1,3-diene 9. This diastereoselectivity is discussed either in terms of a retro-homo-Diels-Alder reaction, associated with thermodynamic control, or with respect to either a competing hetero-Diels-Alder/Claisen or Cope domino pathway, or retro-Claisen/retro-hetero-Diels-Alder of the endo-homo-cycloadducts. These hypothetical mechanisms have been examined by DFT calculations at the MPW1K(CH2 Cl2 )/6-31+G** level of theory for the AlCl3 -mediated cycloadditions of 5d to 2a and 7. Application of Corey's methodology to the γ-halogeno-α-methyl-substituted dienophiles 5a and 5b allowed an enantioselective preparation of known and useful intermediates for the synthesis of either the naturally occurring (-)-β-santalol or its potentially olfactive structural analogs. PMID:25329781

  13. Chemoenzymatic collective synthesis of optically active hydroxyl(methyl)tetrahydronaphthalene-based bioactive terpenoids.

    PubMed

    Batwal, Ramesh U; Argade, Narshinha P

    2015-12-14

    Starting from succinic anhydride and 2-methylanisole, a chemoenzymatic collective formal/total synthesis of several optically active tetrahydronaphthalene based bioactive natural products has been presented via advanced level common precursors; the natural product and antipode (-)/(+)-aristelegone B. Regioselective benzylic oxidations, stereoselective introduction of hydroxyl groups at the α-position of ketone moiety in syn-orientation, efficient enzymatic resolutions with high enantiomeric purity, stereoselective reductions, samarium iodide induced deoxygenations and tandem acylation-Wittig reactions without racemization and/or eliminative aromatization were the key features. An attempted diastereoselective synthesis of (±)-vallapin has also been described. PMID:26419842

  14. Enantiopure N-acyldihydropyridones as synthetic intermediates: asymmetric synthesis of (-)-slaframine.

    PubMed

    Comins, D L; Fulp, A B

    1999-12-16

    [formula: see text] An asymmetric synthesis of (-)-slaframine and N-acetylslaframine has been accomplished starting from an enantiopure dihydropyridone building block. The oxygen-carbon bond at C-1 was incorporated with complete stereoselectivity by using an efficient phenylselenocyclocarbamation reaction. PMID:10836051

  15. Asymmetric formal synthesis of schulzeines A and C.

    PubMed

    Jang, Jaebong; Jung, Jong-Wha; Ahn, Jaeseung; Sim, Jaehoon; Chang, Dong-Jo; Kim, Dae-Duk; Suh, Young-Ger

    2012-07-21

    The asymmetric formal synthesis of schulzeines A and C is described. Key features of the synthesis include the efficient and stereoselective construction of the benzoquinolizidine skeleton via the aza-Claisen rearrangement-induced ring expansion of the 1-vinyl-N-glycyl-isoquinoline, which was prepared by the highly enantioselective asymmetric allylation of the 8-benzyloxy-substituted dihydroisoquinoline and by the acid-catalyzed transannulation of the resulting 10-membered lactam. PMID:22692049

  16. Stereoselective, one-step assembly of the strained protoilludane framework by cobalt-mediated cyclization of an acyclic enediyne precursor. A total synthesis of illudol

    SciTech Connect

    Johnson, E.P.; Vollhardt, K.P.C. )

    1991-01-02

    A number of basidiomycete sesquiterpenoids exhibit considerable toxic, antibiotic, and antitumor activity, including members of the protoilludane, illudane, marasmane, and sterpurane families. The first type is considered to play an important biogenetic role with respect to the remainder. Among the synthetically most challenging protoilludanes ranks illudol (1), because it combines the task of constructing the unusual angular and strained hydrocyclobutaindane nucleus with that of controlling five contiguous stereocenters. The authors report the synthesis of illudol.

  17. Efficient Synthesis of 5-Carboxy-2'-Deoxypyrimidine Nucleoside 5'-Triphosphates.

    PubMed

    Gong, Shan-Shan; Sun, Jian; You, Yue-Hai; Chen, Ji-Zong; Liu, Guo-Dong; Sun, Qi

    2016-06-01

    An efficient P(V)-N activation method for the synthesis of 5-carboxy-2'-deoxyuridine and 5-carboxy-2'-deoxycytidine triphosphates directly from the corresponding phosphoropiperidate precursors has been developed. PMID:27104859

  18. Total Synthesis of Cyclomarin A, a Marine Cycloheptapeptide with Anti-Tuberculosis and Anti-Malaria Activity.

    PubMed

    Barbie, Philipp; Kazmaier, Uli

    2016-01-15

    An efficient synthetic protocol for the stereoselective synthesis of cyclomarin A is reported. Key steps in the syntheses of the building blocks are an asymmetric chelate-enolate Claisen rearrangement, an asymmetric hydrogenation, and highly diastereoselective additions of organozinc and -titanium reagents. PMID:26699807

  19. Nickel-catalyzed synthesis of (E)-olefins from benzylic alcohol derivatives and arylacetonitriles via C-O activation.

    PubMed

    Xiao, Jing; Yang, Jia; Chen, Tieqiao; Han, Li-Biao

    2016-02-01

    An efficient Ni-catalyzed synthesis of (E)-olefins using the readily available benzylic alcohol derivatives and arylacetonitriles is described. This transformation should proceed via a tandem process involving nickel-catalyzed cross coupling via C-O activation and subsequent stereoselective E2 elimination. PMID:26699396

  20. Rapid and Stereoselective Conversion of a "trans"-Cinnamic Acid to a beta-Bromostyrene

    ERIC Educational Resources Information Center

    Evans, Thomas A.

    2006-01-01

    The stereoselective synthesis of an aryl vinyl bromide is accomplished in a rapid microscale reaction of "trans"-4-methoxycinnamic acid with N-bromosuccinimide in dichloromethane. The product is purified by dry column vacuum chromatography and its stereochemistry is determined by [superscript 1]H NMR. TLC, GC and GC-MSD can also be used. This…

  1. Stereoselective synthesis of cis- and trans-2,3-disubstituted tetrahydrofurans via oxonium-prins cyclization: access to the cordigol ring system.

    PubMed

    Spivey, Alan C; Laraia, Luca; Bayly, Andrew R; Rzepa, Henry S; White, Andrew J P

    2010-03-01

    SnBr(4)-promoted oxonium-Prins cyclizations to form 2,3-disubstituted tetrahydrofurans (THFs) are reported. In the absence of an internal nucleophile, the carbocation intermediates are trapped by bromide to give 2,3-cis- and 2,3-trans-configured products; two variations with intramolecular trapping are also reported. One of these allows a single-step stereocontrolled synthesis of the core 2,3-cis-THF ring system of cordigol, a fungicidal polyphenol from the stem bark of Cordia goetzei. For this latter transformation, a stepwise oxonium-Prins/cation trapping pathway rather than orthoquinonemethide formation/hetero-Diels-Alder cycloaddition is supported computationally. PMID:20143863

  2. An Efficient Total Synthesis of Ammosamide B

    PubMed Central

    Reddy, P. V. Narasimha; Banerjee, Biplab; Cushman, Mark

    2010-01-01

    A total synthesis of ammosamide B, a metabolite of the marine-derived Streptomyces strain CNR-698, has been executed in nine steps and 6.9% overall yield. The key step involves the condensation of a 4,6-diBoc protected 1,3,4,6-tetraaminobenzene derivative with dimethyl 2-ketoglutaconate, which effectively constructs the pyrrolidinone ring and the quinoline ring in a single step. This contributes a unique approach to the synthesis of pyrroloquinoline alkaloids that offers the advantages of brevity and relatively high overall yield. PMID:20515072

  3. Total synthesis of (-)-spinosyn A: examination of structural features that govern the stereoselectivity of the key transannular Diels-Alder reaction.

    PubMed

    Winbush, SusAnn M; Mergott, Dustin J; Roush, William R

    2008-03-01

    A study of elements of stereochemical control in transannular Diels-Alder reactions leading to the decahydro-as-indacene core of (-)-spinosyn A is described. Initial studies focused on macrocyclic pentaene 9, which includes C(6)-Br and C(8)-OTBS substituents. Excellent selectivity (>95:5) was observed in the cycloaddition of 9 as a consequence of 1,3-allylic strain interactions involving the C(6) and C(8) substituents in the disfavored TS-2. The major cycloadduct 22 was used in a formal synthesis of (-)-spinosyn A. The TDA cyclizations of 12 (which lacks the C(8)-OTBS unit of 9), 13 (which lacks the C(6)-Br substituent of 12), and 14 (which lacks the C(6)-Br and C(21)-Et substituents of 12) were also studied. Macrocycles 12 and 13 served as precursors to (-)-spinosyn A and the (-)-spinosyn A aglycon (34), respectively. It is striking that substrates 12-14 give very similar distributions of transannular Diels-Alder cycloadducts, indicating that the C(6)-Br and C(21)-stereocenter do not play a significant role in the diastereoselectivity of the TDA cycloaddition of spinosyn A precursor 12. It is likely that some as yet unidentified conformational or structural features of macrocycles 12-14 contribute to the levels of diastereoselectivity achieved, since these TDA reactions are more selective for the C(7)-C(9) stereochemical relationship found in the natural product than are the IMDA reactions of trienes 4 and 7. PMID:18215065

  4. Practical asymmetric synthesis of the herbicide (S)-indanofan via lipase-catalyzed kinetic resolution of a diol and stereoselective acid-catalyzed hydrolysis of a chiral epoxide.

    PubMed

    Tanaka, Ken; Yoshida, Kenji; Sasaki, Chiduko; Osano, Yasuko T

    2002-05-01

    Racemic indanofan [(+/-)-1] was efficiently converted to enantiopure (S)-indanofan [(S)-1] by a combination of enzymatic resolution and chemical inversion techniques. An additional important technique is the use of an o-xylene complex of a hemiketal (S)-3c as a precursor, which can be quantitatively converted to (S)-indanofan and easily purified by recrystallization from o-xylene. PMID:11975580

  5. Stereoselective Synthesis of Diazabicyclic β-Lactams through Intramolecular Amination of Unactivated C(sp(3))-H Bonds of Carboxamides by Palladium Catalysis.

    PubMed

    Zhang, Shi-Jin; Sun, Wen-Wu; Cao, Pei; Dong, Xiao-Ping; Liu, Ji-Kai; Wu, Bin

    2016-02-01

    An efficient C(sp(3))-H bond activation and intramolecular amination reaction via palladium catalysis at the β-position of carboxyamides to make β-lactams was described. The investigation of the substrate scope showed that the current reaction conditions favored activation of the β-methylene group. Short sequences were developed for preparation of various diazabicyclic β-lactam compounds with this method as the key step from chiral proline and piperidine derivatives. PMID:26745308

  6. Stereoselective Microbial Dehalorespiration with Vicinal Dichlorinated Alkanes

    PubMed Central

    De Wildeman, Stefaan; Diekert, Gabriele; Van Langenhove, Herman; Verstraete, Willy

    2003-01-01

    The suspected carcinogen 1,2-dichloroethane (1,2-DCA) is the most abundant chlorinated C2 groundwater pollutant on earth. However, a reductive in situ detoxification technology for this compound does not exist. Although anaerobic dehalorespiring bacteria are known to catalyze several dechlorination steps in the reductive-degradation pathway of chlorinated ethenes and ethanes, no appropriate isolates that selectively and metabolically convert them into completely dechlorinated end products in defined growth media have been reported. Here we report on the isolation of Desulfitobacterium dichloroeliminans strain DCA1, a nutritionally defined anaerobic dehalorespiring bacterium that selectively converts 1,2-dichloroethane and all possible vicinal dichloropropanes and -butanes into completely dechlorinated end products. Menaquinone was identified as an essential cofactor for growth of strain DCA1 in pure culture. Strain DCA1 converts chiral chlorosubstrates, revealing the presence of a stereoselective dehalogenase that exclusively catalyzes an energy-conserving anti mechanistic dichloroelimination. Unlike any known dehalorespiring isolate, strain DCA1 does not carry out reductive hydrogenolysis reactions but rather exclusively dichloroeliminates its substrates. This unique dehalorespiratory biochemistry has shown promising application possibilities for bioremediation purposes and fine-chemical synthesis. PMID:12957955

  7. Cu-Catalyzed Multicomponent Reaction of Styrenes, Perfluoroalkyl Halide, Alcohol, and tert-Butyl Hydroperoxide: One-Pot Synthesis of (Z)-β-Alkoxyperfluoroalkenone.

    PubMed

    Luo, Qiang; Liu, Chunmei; Tong, Jingjing; Shao, Ying; Shan, Wenyu; Wang, Hanghang; Zheng, Hao; Cheng, Jiang; Wan, Xiaobing

    2016-04-15

    An efficient synthesis of Z-perfluoroalkyl-substituted enones by a multicomponent reaction strategy has been described. A variety of elusive perfluoroalkylated enones are furnished under mild reaction conditions in good yields with unique chemo- and stereoselectivity. A sequence of radical-mediated Kornblum-DeLaMare reaction, Michael addition, and HF elimination is proposed for the mechanism. PMID:26980724

  8. Efficient synthesis of esermethole and its analogues.

    PubMed

    Zhou, Yongyun; Zhao, Yuanhong; Dai, Xiaoyong; Liu, Jianping; Li, Liang; Zhang, Hongbin

    2011-06-01

    In this work, a general and flexible synthetic route towards the synthesis of pyrroloindoline alkaloids was developed. This new strategy features with a palladium mediated sequential arylation-allylation of o-bromoanilides and leads to the construction of oxindoles bearing a full carbon quaternary center. The cheap triphenylphosphine was proved to be a highly effective ligand for this one pot transformation. On the basis of this new method, esermethole and its analogues were synthesized. PMID:21472186

  9. An Efficient Microscale Procedure for the Synthesis of Aspirin

    NASA Astrophysics Data System (ADS)

    Pandita, Sangeeta; Goyal, Samta

    1998-06-01

    The synthesis of aspirin is a part of many undergraduate organic synthesis labs and is frequently used in qualitative organic analysis laboratory for the identification of salicylic acid. We have found that aspirin can be synthesized on microscale by a simple and efficient procedure that eliminates the heating step employed in literature procedures and gives a pure, ferric-negative product (no purple color with alcoholic ferric chloride solution).

  10. Applications of cationic aza-cope rearrangements for alkaloid synthesis. Stereoselective preparation of cis-3a-aryloctahydroindoles and a new short route to amaryllidaceae alkaloids. [cis-3a-aryloctahydroindoles

    SciTech Connect

    Overman, L.E.; Mendelson, L.T.; Jacobsen, E.J.

    1983-11-02

    A new synthesis of cis-3a-aryloctahydroindoles is detailed. The key step is a ring-enlarging pyrrolidine annulation reaction which occurs when 2-amino-1-(1-arylethenyl)cyclopentanols are treated under mild conditions with an aldehyde and acid. Three different methods (Schemes I-III) for assemblying the 2-amino(1-arylethenyl)cyclopentanol intermediates are reported. An efficient formal total synthesis of the Amaryllidaceae alkaloid (+-)-crinine (Scheme III) is reported, in which key intermediate 26 was assembled with virtually complete stereocontrol in four steps and 44% overall yield from readily available 1,2-bis(trimethylsilyoxy)cyclopentene.

  11. Oxidative Prins and Prins/Friedel-Crafts cyclizations for the stereoselective synthesis of dioxabicycles and hexahydro-1H-benzo[f]isochromenes via the benzylic C-H activation.

    PubMed

    Reddy, B V Subba; Borkar, Prashant; Yadav, J S; Reddy, P Purushotham; Kunwar, A C; Sridhar, B; Grée, René

    2012-02-21

    1-Benzyl ethers of (E)- and (Z)-hex-3-en-1,6-diols and hept-3-en-1,7-diols undergo a smooth oxidative cyclization with DDQ in the presence of In(OTf)(3) through a sequential C-H bond activation and an intramolecular Prins cyclization to afford the corresponding trans- and cis-fused hexahydro-2H-furo[3,2-c]pyrans and octahydropyrano[4,3-b]pyrans respectively in good yields with an excellent stereoselectivity. Aryl tethered homoallylbenzyl ethers such as benzyl ethers of (E)- and (Z)-6-arylhex-3-enyl alcohols undergo a tandem Prins/Friedel-Crafts cyclization in the presence of stoichiometric amounts of DDQ and SnCl(4)via the benzylic C-H bond activation to furnish the corresponding trans- and cis-fused hexahydro-1H-benzo[f]isochromenes in good yields with complete stereoselectivity. PMID:22187046

  12. The Total Synthesis of Inostamycin A.

    PubMed

    Yu, Guangri; Jung, Byunghyuck; Lee, Hee-Seung; Kang, Sung Ho

    2016-02-12

    The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8, respectively, in which the use of LaCl3 for transmetallation was critical for high coupling efficiency. PMID:26800259

  13. Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis

    PubMed Central

    Brabham, Robin

    2016-01-01

    Abstract The utility of sulfoxides in a diverse range of transformations in the field of carbohydrate chemistry has seen rapid growth since the first introduction of a sulfoxide as a glycosyl donor in 1989. Sulfoxides have since developed into more than just anomeric leaving groups, and today have multiple roles in glycosylation reactions. These include as activators for thioglycosides, hemiacetals, and glycals, and as precursors to glycosyl triflates, which are essential for stereoselective β‐mannoside synthesis, and bicyclic sulfonium ions that facilitate the stereoselective synthesis of α‐glycosides. In this review we highlight the mechanistic investigations undertaken in this area, often outlining strategies employed to differentiate between multiple proposed reaction pathways, and how the conclusions of these investigations have and continue to inform upon the development of more efficient transformations in sulfoxide‐based carbohydrate synthesis. PMID:26744250

  14. Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars.

    PubMed

    Albler, Christopher; Hollaus, Ralph; Kählig, Hanspeter; Schmid, Walther

    2014-01-01

    Higher aminosugars are interesting targets in carbohydrate synthesis since these compounds play important roles in biological systems. However, their availability from natural sources is limited. Thus, in order to investigate their biological function, the development of facile and adaptable routes to this class of compounds is of fundamental importance. Our synthetic route towards these target molecules makes use of readily accessible pentoses and hexoses, which are subjected to indium-mediated two-carbon chain elongation. Subsequent ozonolysis and treatment with base yields α,β-unsaturated aldehydes, which are stereoselectively epoxidized using Jørgenson's protocol. After Wittig chain elongation the obtained allylic epoxides were regio- and stereoselectively opened with trimethylsilyl azide under palladium catalysis. Finally, a suitable deprotection protocol, starting with acidic acetate cleavage and ozonolysis was established. Peracetylation of the products simplifies purification and subsequent azide reduction followed by final deacetylation using methanolic sodium methoxide furnishes the title compounds. PMID:25246982

  15. Efficient synthesis of the antigenic phosphoglycans of the Leishmania parasite.

    PubMed

    Ruhela, D; Vishwakarma, R A

    2001-10-01

    Antigenic phosphoglycan repeats of the Leishmania parasite can be assembled in a flexible and efficient manner without involving any glycosidation steps, and the chain can be extended either towards the non-reducing (6'-OH) or reducing (1-OH) end suitable for synthesis of lipophosphoglycan, proteophosphoglycan and analogues. PMID:12240271

  16. Selective synthesis of either enantiomer of an anti-breast cancer agent via a common enantioenriched intermediate

    PubMed Central

    Johnson, Aaron George; Tranquilli, Marissa M.; Harris, Michael R.; Jarvo, Elizabeth R.

    2015-01-01

    A stereoselective synthesis of a bioactive triarylmethane is described. Key to the synthesis is a nickel-catalyzed Suzuki-Miyaura coupling which proceeds with retention at the benzylic center. This method is complementary to our previously reported nickel-catalyzed Kumada coupling which proceeds with inversion. Together, the two methods allow for efficient access to either enantiomer of biologically relevant triarylmethanes from a common enantioenriched intermediate. PMID:26085695

  17. Structure elucidation via stereoselective synthesis of the acetate center of 1-Azabicyclo[2.2.2]oct-3-yl {alpha}-hydroxy-{alpha}(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP). A high affinity muscarinic imaging agent for SPECT

    SciTech Connect

    McPherson, D.W.; Knapp, F.F. Jr.

    1996-11-15

    A facile stereoselective synthesis of {alpha}-hydroxy-{alpha}-phenyl-{alpha}-(1-propyn-3-yl)acetic acid in high enantiomeric excess has been developed and allows determination of the (R/S) conformation at this center. In addition, comparison of the specific rotation, HPLC, and NMR data of (E)-(R,R)-and (E)-(R,S)-IQNP to those prepared by a classical resolution of the acetate moiety allows the assignment of (E)-(R,R)-IQNP as the isomer demonstrating binding to the M{sub 1} mAChR subtype and (Z)-(R,R)-IQNP as the isomer binding to both the M{sub 1} and M{sub 2} mAChR subtypes.

  18. Stereoselective synthesis: Molecular editing of carbohydrates

    NASA Astrophysics Data System (ADS)

    McNally, Andrew

    2015-07-01

    Deoxygenation reactions have been used to convert biomass-derived carbohydrates into useful platform chemicals. Now, a method has been described that can selectively excise C-O bonds to produce valuable chiral synthons.

  19. Total Synthesis of a Diacetonide Derivative of Thuggacin A.

    PubMed

    Yadav, Jhillu S; Dutta, Palash

    2016-03-01

    A highly stereoselective total synthesis of the diacetonide derivative of the antibiotic thuggacin A has been described. The synthesis features the stereoselective Stille cross-coupling reaction to set up the whole carbon framework, aldol condensation to construct the highly substituted conjugated diene, non-Evans syn aldol, CBS reduction, Hantzsch's thiazole synthesis, Horner-Wadsworth-Emmons reaction, and Shiina's macrolactonization. PMID:26856208

  20. Synthesis of a Precursor to Sacubitril Using Enabling Technologies.

    PubMed

    Lau, Shing-Hing; Bourne, Samuel L; Martin, Benjamin; Schenkel, Berthold; Penn, Gerhard; Ley, Steven V

    2015-11-01

    An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3·HCl) over 7 steps in 54% overall yield. PMID:26509957

  1. Stereoselective synthesis of 2,3-disubstituted indoline, pyrrolidine and cyclic ether-fused 1,2-dihydroquinoline derivatives using alkyne iminium ion cyclization of vinylogous carbamates: switch of regioselectivity using an internal hydroxy group as a nucleophile.

    PubMed

    Gharpure, Santosh J; Prasath, V; Kumar, Vinod

    2015-09-14

    An intramolecular, alkyne iminium ion cyclization of vinylogous carbamates derived from o-alkynyl anilines and N-protected homopropargyl amines is developed for the stereoselective construction of trans-2,3-disubstituted indolines and pyrrolidine derivatives, respectively. The regioselectivity of the alkyne iminium ion cyclization could be switched using a hydroxy group as an internal nucleophile resulting in cyclic ether-fused 1,2-dihydroquinolines. The entire process of nitrogen heterocycle formation can also be carried out in a 'one-pot' manner starting from o-iodo aniline derivatives. PMID:26226402

  2. Copper(I)-Y Zeolite-Catalyzed Regio- and Stereoselective [2 + 2 + 2] Cyclotrimerization Cascade: An Atom- and Step-Economical Synthesis of Pyrimido[1,6-a]quinoline.

    PubMed

    Ramanathan, Devenderan; Pitchumani, Kasi

    2015-10-16

    An elegant copper(I)-Y zeolite-catalyzed tandem process, involving ketenimine-based termolecular [2 + 2 + 2]/[NC + CC + NC] cycloaddition, using sulfonyl azide, alkyne, and quinoline, to prepare pyrimido[1,6-a]quinolines is reported. In this straightforward, highly atom- and step-economical protocol, copper(I) promotes for azide-alkyne [3 + 2] cycloaddition which is followed by ring-rearrangement/ketenimine formation/regio- and stereoselective [2 + 2 + 2] termolecular cycloaddition and dehydrogenation cascade to yield selectively the E-isomer of pyrimido[1,6-a]quinoline. PMID:26390020

  3. Total Synthesis of (±)-Englerin A Using An Intermolecular [3+2] Cycloaddition Reaction of Platinum-Containing Carbonyl Ylide.

    PubMed

    Kusama, Hiroyuki; Tazawa, Aoi; Ishida, Kento; Iwasawa, Nobuharu

    2016-01-01

    Total synthesis of (±)-Englerin A has been achieved starting from γ,δ-ynone 5 in 14 steps. The key feature of this synthesis is the highly efficient and stereoselective preparation of 8-oxabicyclo[3.2.1]octane derivative 6, a core skeleton of Englerin A, based on an inverse electron-demand [3+2] cycloaddition reaction of the platinum-containing carbonyl ylide, which was developed in our laboratory. PMID:26377511

  4. A Multi-Enzymatic Cascade Reaction for the Stereoselective Production of γ-Oxyfunctionalyzed Amino Acids.

    PubMed

    Enoki, Junichi; Meisborn, Jaqueline; Müller, Ann-Christin; Kourist, Robert

    2016-01-01

    A stereoselective three-enzyme cascade for synthesis of diasteromerically pure γ-oxyfunctionalized α-amino acids was developed. By coupling a dynamic kinetic resolution (DKR) using an N-acylamino acid racemase (NAAAR) and an L-selective aminoacylase from Geobacillus thermoglucosidasius with a stereoselective isoleucine dioxygenase from Bacillus thuringiensis, diastereomerically pure oxidized amino acids were produced from racemic N-acetylamino acids. The three enzymes differed in their optimal temperature and pH-spectra. Their different metal cofactor dependencies led to inhibitory effects. Under optimized conditions, racemic N-acetylmethionine was quantitatively converted into L-methionine-(S)-sulfoxide with 97% yield and 95% de. The combination of these three different biocatalysts allowed the direct synthesis of diastereopure oxyfunctionalized amino acids from inexpensive racemic starting material. PMID:27092111

  5. A Multi-Enzymatic Cascade Reaction for the Stereoselective Production of γ-Oxyfunctionalyzed Amino Acids

    PubMed Central

    Enoki, Junichi; Meisborn, Jaqueline; Müller, Ann-Christin; Kourist, Robert

    2016-01-01

    A stereoselective three-enzyme cascade for synthesis of diasteromerically pure γ-oxyfunctionalized α-amino acids was developed. By coupling a dynamic kinetic resolution (DKR) using an N-acylamino acid racemase (NAAAR) and an L-selective aminoacylase from Geobacillus thermoglucosidasius with a stereoselective isoleucine dioxygenase from Bacillus thuringiensis, diastereomerically pure oxidized amino acids were produced from racemic N-acetylamino acids. The three enzymes differed in their optimal temperature and pH-spectra. Their different metal cofactor dependencies led to inhibitory effects. Under optimized conditions, racemic N-acetylmethionine was quantitatively converted into L-methionine-(S)-sulfoxide with 97% yield and 95% de. The combination of these three different biocatalysts allowed the direct synthesis of diastereopure oxyfunctionalized amino acids from inexpensive racemic starting material. PMID:27092111

  6. An efficient and sustainable synthesis of NHC gold complexes.

    PubMed

    Johnson, Alice; Gimeno, M Concepción

    2016-08-11

    A simple, efficient and sustainable method for the general synthesis of NHC gold(i) complexes is described. The reaction of imidazolium salts, of different electronic and steric requirements, with [AuX(tht)] (tht = tetrahydrothiophene) derivatives, in the presence of NBu4(acac), in air and at room temperature leads to the NHC gold species in good yields and with very short reaction times. PMID:27401053

  7. Enantioselective organocatalytic reduction of β-trifluoromethyl nitroalkenes: an efficient strategy for the synthesis of chiral β-trifluoromethyl amines.

    PubMed

    Massolo, Elisabetta; Benaglia, Maurizio; Orlandi, Manuel; Rossi, Sergio; Celentano, Giuseppe

    2015-02-23

    An efficient organocatalytic stereoselective reduction of β-trifluoromethyl-substituted nitroalkenes, mediated by 3,5-dicarboxylic ester-dihydropyridines (Hantzsch ester type), has been successfully developed. A multifunctional thiourea-based (S)-valine derivative was found to be the catalyst of choice, promoting the reaction in up to 97% ee. The methodology has been applied to a wide variety of substrates, leading to the formation of differently substituted precursors of enantiomerically enriched β-trifluoromethyl amines. The mechanism of the reaction and the mode of action of the metal-free catalytic species were computationally investigated; on the basis of DFT transition-state (TS) analysis, a model of stereoselection was also proposed. PMID:25573847

  8. Regio- and stereoselectivities in plant cell biotransformation

    SciTech Connect

    Hamada, H.

    1995-12-01

    The ability of plant cultured cells to convert foreign substrates into more useful substances is of considerable interest. Therefore I have studied biotransformation of foreign substrate by plant cell suspension cultures. In this presentation, I report regio- and stereoselectivities in biotransformation of steroids and indole alkaloids and taxol by plant (tobacco, periwinkle, moss, orchid) cell suspension cultures.

  9. Stereoselective intermolecular C-H amination reactions.

    PubMed

    Lebel, Hélène; Trudel, Carl; Spitz, Cédric

    2012-08-14

    A novel chiral N-mesyloxycarbamate to perform rhodium-catalyzed stereoselective C-H amination reactions is reported. Chiral benzylic and propargylic amines are produced in good yields and selectivities using ethyl acetate as solvent. The corresponding free amines are easily obtained by cleavage of the chiral reagent, which could also be recovered. PMID:22751570

  10. Energy efficiency in nanoscale synthesis using nanosecond plasmas

    PubMed Central

    Pai, David Z.; (Ken) Ostrikov, Kostya; Kumar, Shailesh; Lacoste, Deanna A.; Levchenko, Igor; Laux, Christophe O.

    2013-01-01

    We report a nanoscale synthesis technique using nanosecond-duration plasma discharges. Voltage pulses 12.5 kV in amplitude and 40 ns in duration were applied repetitively at 30 kHz across molybdenum electrodes in open ambient air, generating a nanosecond spark discharge that synthesized well-defined MoO3 nanoscale architectures (i.e. flakes, dots, walls, porous networks) upon polyamide and copper substrates. No nitrides were formed. The energy cost was as low as 75 eV per atom incorporated into a nanostructure, suggesting a dramatic reduction compared to other techniques using atmospheric pressure plasmas. These findings show that highly efficient synthesis at atmospheric pressure without catalysts or external substrate heating can be achieved in a simple fashion using nanosecond discharges. PMID:23386976

  11. Efficient synthesis of longer Aβ peptides via removable backbone modification.

    PubMed

    Zuo, Chao; Tang, Shan; Si, Yan-Yan; Wang, Zhipeng A; Tian, Chang-Lin; Zheng, Ji-Shen

    2016-06-14

    Longer amyloid-beta (Aβ) peptides (43 to 49 amino acids) play essential roles in the pathology of Alzheimer's disease (AD). The difficulty in the preparation of longer Aβ peptides is still an obstacle to elucidate their roles in AD. Herein we report a robust and efficient strategy for the chemical synthesis of longer Aβ peptides (Aβ48 and Aβ49). A key feature of this method is the installation of removable Arg4-tagged backbone modification groups into the hydrophobic region of Aβ. This modification can improve the handling properties of the purification, ligation and mass characterization of longer Aβ peptides. The practicability of the new method has been demonstrated by the successful synthesis of Aβ48 and Aβ49 peptides. PMID:27188564

  12. The first asymmetric synthesis of marliolide from readily accessible carbohydrate as chiral template.

    PubMed

    Mailar, Karabasappa; Choi, Won Jun

    2016-09-01

    A simple and efficient strategy for the first asymmetric total synthesis of marliolide was accomplished by using stereoselective alkylation of the dianion of the β-hydroxy lactone enolate with myristyl aldehyde as a key step. The key intermediate, β-hydroxyl γ-methyl butyrolactone was prepared by transformation of L-lyxonolactone starting from D-ribose, a naturally abundant chiral carbohydrate. PMID:27356234

  13. Nickel-Catalyzed Regioselective Cleavage of Csp(2)-S Bonds: Method for the Synthesis of Tri- and Tetrasubstituted Alkenes.

    PubMed

    Chen, Jinyang; Chen, Sihai; Xu, Xinhua; Tang, Zhi; Au, Chak-Tong; Qiu, Renhua

    2016-04-15

    We describe here an efficient route for the synthesis of (Z)-vinylic sulfides 3 via the highly regio- and stereoselective coupling of (Z)-1,2-bis(aryl(alkyl)thio)alkenes and Grignard reagents over a Ni catalyst under mild conditions. (Z)-Vinylic sulfides 3 are important intermediates in the synthesis of tri- and tetrasubstituted alkenes that are important construction blocks for drugs and natural products. The directing organosulfur groups (SR) can be converted to diaryl(alkyl) disulfides (RSSR) using H2O2 as oxidant, hence avoiding the waste of sulfur resources. The protocol provides a general method that is highly regio- and stereoselective for the synthesis of a diversity of tri- and tetrasubstituted alkenes. PMID:26999304

  14. Microbial transformations of warfarin: stereoselective reduction by Nocardia corallina and Arthrobacter species.

    PubMed Central

    Davis, P J; Rizzo, J D

    1982-01-01

    The microbiological metabolism of warfarin was examined as a model of metabolism in higher organisms, including humans, and to determine the chirality of microbial reductases for application in organic synthesis. Nineteen cultures were examined based on their reported abilities to reduce ketonic substrates, and several were shown to catalyze the desired reaction. Nocardia corallina (ATCC 19070) exhibited complete substrate and product stereoselectivity as it reduced S-warfarin to the corresponding S-alcohol. Arthrobacter species (ATCC 19140) exhibited marked substrate and complete product stereoselectivity since S-warfarin, and to a lesser extent R-warfarin, were reduced to the corresponding S-alcohols. These reductions parallel those reported to occur in mammalian species. PMID:7081986

  15. Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides

    PubMed Central

    2016-01-01

    The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products. PMID:27350334

  16. A simple, universal, efficient PCR-based gene synthesis method: sequential OE-PCR gene synthesis.

    PubMed

    Zhang, Pingping; Ding, Yingying; Liao, Wenting; Chen, Qiuli; Zhang, Huaqun; Qi, Peipei; He, Ting; Wang, Jinhong; Deng, Songhua; Pan, Tianyue; Ren, Hao; Pan, Wei

    2013-07-25

    Herein we present a simple, universal, efficient gene synthesis method based on sequential overlap extension polymerase chain reactions (OE-PCRs). This method involves four key steps: (i) the design of paired complementary 54-mer oligonucleotides with 18 bp overlaps, (ii) the utilisation of sequential OE-PCR to synthesise full-length genes, (iii) the cloning and sequencing of four positive T-clones of the synthesised genes and (iv) the resynthesis of target genes by OE-PCR with correct templates. Mispriming and secondary structure were found to be the principal obstacles preventing successful gene synthesis and were easily identified and solved in this method. Compensating for the disadvantages of being laborious and time-consuming, this method has many attractive advantages, such as the ability to guarantee successful gene synthesis in most cases and good allowance for Taq polymerase, oligonucleotides, PCR conditions and a high error rate. Thus, this method provides an alternative tool for individual gene synthesis without strict needs of the high-specialised experience. PMID:23597923

  17. A novel and practical asymmetric synthesis of dapoxetine hydrochloride.

    PubMed

    Zhu, Yijun; Liu, Zhenren; Li, Hongyan; Ye, Deyong; Zhou, Weicheng

    2015-01-01

    A novel and practical asymmetric synthesis of dapoxetine hydrochloride by using the chiral auxiliary (S)-tert-butanesulfinamide was explored. The synthesis was concise, mild, and easy to perform. The overall yield and stereoselectivity were excellent. PMID:26734109

  18. A novel and practical asymmetric synthesis of dapoxetine hydrochloride

    PubMed Central

    Zhu, Yijun; Liu, Zhenren; Li, Hongyan

    2015-01-01

    Summary A novel and practical asymmetric synthesis of dapoxetine hydrochloride by using the chiral auxiliary (S)-tert-butanesulfinamide was explored. The synthesis was concise, mild, and easy to perform. The overall yield and stereoselectivity were excellent. PMID:26734109

  19. Framework for efficient synthesis of spatially embedded morphologies.

    PubMed

    Vanherpe, Liesbeth; Kanari, Lida; Atenekeng, Guy; Palacios, Juan; Shillcock, Julian

    2016-08-01

    Many problems in science and engineering require the ability to grow tubular or polymeric structures up to large volume fractions within a bounded region of three-dimensional space. Examples range from the construction of fibrous materials and biological cells such as neurons, to the creation of initial configurations for molecular simulations. A common feature of these problems is the need for the growing structures to wind throughout space without intersecting. At any time, the growth of a morphology depends on the current state of all the others, as well as the environment it is growing in, which makes the problem computationally intensive. Neuron synthesis has the additional constraint that the morphologies should reliably resemble biological cells, which possess nonlocal structural correlations, exhibit high packing fractions, and whose growth responds to anatomical boundaries in the synthesis volume. We present a spatial framework for simultaneous growth of an arbitrary number of nonintersecting morphologies that presents the growing structures with information on anisotropic and inhomogeneous properties of the space. The framework is computationally efficient because intersection detection is linear in the mass of growing elements up to high volume fractions and versatile because it provides functionality for environmental growth cues to be accessed by the growing morphologies. We demonstrate the framework by growing morphologies of various complexity. PMID:27627420

  20. Donor Substrate Regeneration for Efficient Synthesis of Globotetraose and Isoglobotetraose

    PubMed Central

    Shao, Jun; Zhang, Jianbo; Kowal, Przemyslaw; Wang, Peng George

    2002-01-01

    Here we describe the efficient synthesis of two oligosaccharide moieties of human glycosphingolipids, globotetraose (GalNAcβ1→3Galα1→4Galβ1→4Glc) and isoglobotetraose (GalNAcβ1→3Galα1→3Galβ1→4Glc), with in situ enzymatic regeneration of UDP-N-acetylgalactosamine (UDP-GalNAc). We demonstrate that the recombinant β-1,3-N-acetylgalactosaminyltransferase from Haemophilus influenzae strain Rd can transfer N-acetylgalactosamine to a wide range of acceptor substrates with a terminal galactose residue. The donor substrate UDP-GalNAc can be regenerated by a six-enzyme reaction cycle consisting of phosphoglucosamine mutase, UDP-N-acetylglucosamine pyrophosphorylase, phosphate acetyltransferase, pyruvate kinase, and inorganic pyrophosphatase from Escherichia coli, as well as UDP-N-acetylglucosamine C4 epimerase from Plesiomonas shigelloides. All these enzymes were overexpressed in E. coli with six-histidine tags and were purified by one-step nickel-nitrilotriacetic acid affinity chromatography. Multiple-enzyme synthesis of globotetraose or isoglobotetraose with the purified enzymes was achieved with relatively high yields. PMID:12406759

  1. Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

    PubMed Central

    Matthessen, Roman; Fransaer, Jan; Binnemans, Koen

    2014-01-01

    Summary The near-unlimited availability of CO2 has stimulated a growing research effort in creating value-added products from this greenhouse gas. This paper presents the trends on the most important methods used in the electrochemical synthesis of carboxylic acids from carbon dioxide. An overview is given of different substrate groups which form carboxylic acids upon CO2 fixation, including mechanistic considerations. While most work focuses on the electrocarboxylation of substrates with sacrificial anodes, this review considers the possibilities and challenges of implementing other synthetic methodologies. In view of potential industrial application, the choice of reactor setup, electrode type and reaction pathway has a large influence on the sustainability and efficiency of the process. PMID:25383120

  2. Radical additions to chiral hydrazones: stereoselectivity and functional group compatibility.

    PubMed

    Friestad, Gregory K

    2012-01-01

    Free radical additions to imino compounds offer increased synthetic accessibility of chiral amines, but lack of general methods for stereocontrol has hindered their development. This review focuses on two asymmetric amine synthesis strategies designed to address this problem, with emphasis on addition of functionalized radicals which may facilitate applications to synthesis of complex targets. First, chiral N-acylhydrazones are acceptors for intermolecular radical additions of a wide range of primary, secondary, and tertiary alkyl halides to the C=N bond, with radicals generated under manganese-, tin-, or boron-mediated conditions. A variety of aldehydes and ketones serve as viable precursors for the chiral hydrazones, and the highly stereoselective reactions tolerate electrophilic functionality in both coupling components. Second, radical precursors may be linked to chiral α-hydroxyhydrazones via a silicon tether to the hydroxyl group; conformational constraints impart stereocontrol during 5-exo radical cyclization under stannyl- or thiyl-mediated conditions. The silicon tether may later be removed to reveal the formal adducts of hydroxymethyl, vinyl, acetyl, and 2-oxoethyl radicals to the C=N bond. Methodology development and applications to biologically important targets are discussed. PMID:21842359

  3. Ir-Catalyzed Regio- and Stereoselective Hydrosilylation of Internal Thioalkynes: A Combined Experimental and Computational Study.

    PubMed

    Song, Li-Juan; Ding, Shengtao; Wang, Yong; Zhang, Xinhao; Wu, Yun-Dong; Sun, Jianwei

    2016-08-01

    Iridium complexes are known catalysts for a range of silylation reactions. However, the exploitation for selective hydrosilylation of unsymmetrical internal alkynes has been limitedly known. Described here is a new example of this type. Specifically, [(cod)IrCl]2 catalyzes the efficient and mild hydrosilylation of thioalkynes by various silanes with excellent regio- and stereoselectivity. DFT studies suggested a new mechanism involving Ir(I) hydride as the key intermediate. PMID:27232905

  4. Heterogeneous Diastereoselective Catalysis--A Powerful Strategy Toward C(15) Stereoselectivity from PGF2α Analogues Structure.

    PubMed

    Coman, Simona M; Parvulescu, Vasile I

    2015-01-01

    A major trend in fine chemicals and pharmaceuticals is the synthesis of molecules with increased complexity. This trend translates the aim of organic syntheses to conditions in which high degrees of chemo-, regio- and stereoselectivity can be provided. In this context, the chemoselective hydrogenation of one functional group in the presence of other reactive groups is a frequently encountered problem in fine chemicals manufacture. This study provides a critical analysis including elegant examples of reactions in which high chemo- and diastereoselectivities were achieved in the hydrogenation of a C=O group in the presence of C=C double bond. A particular emphasis is addressed to the stereoselective C(15) synthesis from Cloprostenol--a PGF2α structural analogue. PMID:26553252

  5. Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

    PubMed Central

    Minko, Yury; Pasco, Morgane; Chechik, Helena

    2013-01-01

    Summary The carbocupration reactions of heterosubstituted alkynes allow the regio- and stereoselective formation of vinyl organometallic species. N-Alkynylamides (ynamides) are particularly useful substrates for the highly regioselective carbocupration reaction, as they lead to the stereodefined formation of vinylcopper species geminated to the amide moiety. The latter species are involved in numerous synthetically useful transformations leading to valuable building blocks in organic synthesis. Here we describe in full the results of our studies related to the carbometallation reactions of N-alkynylamides. PMID:23616793

  6. Synthesis of all nineteen appropriately protected chiral alpha-hydroxy acid equivalents of the alpha-amino acids for Boc solid-phase depsi-peptide synthesis.

    PubMed

    Deechongkit, Songpon; You, Shu-Li; Kelly, Jeffery W

    2004-02-19

    [reaction: see text] The preparation of depsi-peptides, amide-to-ester-substituted peptides used to probe the role of hydrogen bonding in protein folding energetics, is accomplished by replacing specific l-alpha-amino acid residues by their alpha-hydroxy acid counterparts in a solid-phase synthesis employing a t-Boc strategy. Herein we describe the efficient stereoselective synthesis of all 19 appropriately protected alpha-hydroxy acid equivalents of the l-alpha-amino acids, employing commercially available materials, expanding the number of available alpha-hydroxy acids from 9 to 19. PMID:14961607

  7. On the stereoselective aminoacylation of RNA

    NASA Technical Reports Server (NTRS)

    Usher, D. A.; Needels, M. C.

    1984-01-01

    Gabbay and Kleinman (1970) have found that stereospecific complex formation (noncovalent) occurs between nucleic acids and a number of derivatives of amino acids. However, until recently, chiral selection in any nonenzymatic RNA-aminoacylation reaction was unknown. Profy and Usher (1984) reported that aminoacylation of the 'internal' 2-prime-ester occurred with a significant amount of stereoselection. Profy and Usher (1984) have also observed that aminoacylation of the 'internal' 2-prime-hydroxyl groups of polyribonucleotides by the imidazolide of N-3,5-dinitrobenzoylalanine occurs with chiral selection. In order to obtain further information regarding the considered phenomena, a systematic investigation was initiated of the factors which contribute to the observed stereoselectivity of the aminoacylation reaction. In the present paper, the effect of a change in the amino acid from alanine to leucine is considered along with an investigation of the D- and L-alanyl internal' 2-prime esters of the dinucleoside monophosphate of 3-prime,5-prime-ApA.

  8. Total Synthesis of (−)-Calyciphylline N

    PubMed Central

    Shvartsbart, Artem; Smith, Amos B.

    2014-01-01

    The total synthesis of the architecturally complex Daphniphyllum alkaloid (−)-calyciphylline N has been achieved. Highlights of the synthesis include a Et2AlCl promoted, highly stereoselective susbtrate controlled intramolecular Diels-Alder reaction, a transannular enolate alkylation, an effective Stille carbonylation/Nazarov cyclization sequence, and a high risk dia-stereoselective hydrogenation of a fully substituted conjugated diene ester. PMID:24319987

  9. Efficient chemoenzymatic synthesis of 4-nitrophenyl β-d-apiofuranoside and its use in screening of β-d-apiofuranosidases.

    PubMed

    Kis, Peter; Potocká, Elena; Mastihuba, Vladimír; Mastihubová, Mária

    2016-07-22

    4-Nitrophenyl β-d-apiofuranoside as a chromogenic probe for detection of β-d-apiofuranosidase activity was prepared in 61% yield from 2,3-isopropylidene-α,β-d-apiofuranose through a sequence of five reactions. The synthesis involves one regioselective enzymatic step-benzoylation of primary hydroxyl of 2,3-isopropylidene-α,β-d-apiofuranose catalysed by Lipolase 100T and stereoselective β-d-apiofuranosylation of p-nitrophenol using BF3⋅OEt2/Et3N. The product was used for screening of β-d-apiofuranosidase activity in 61 samples of crude commercial enzymes and plant materials. Fifteen enzyme preparations originating from different strains of genera Aspergillus display β-d-apiofuranosidase activity. The highest activity was found in Rapidase AR 2000 (78.27 U/g) and lyophilized Viscozyme L (64,36 U/g). PMID:27196312

  10. Iodine catalyzed simple and efficient synthesis of antiproliferative 2-pyridones.

    PubMed

    Buduma, Komuraiah; Chinde, Srinivas; Arigari, Niranjana Kumar; Grover, Paramjit; Srinivas, K V N S; Kotesh Kumar, J

    2016-05-01

    A simple and efficient method for the selective synthesis of 2-pyrdones from 4H-pyrans using iodine as catalyst and ethanol as solvent was developed. The present method is equally effective for both aromatic and hetero aromatic ring containing 4H-pyrans. The compatibility with various functional groups, mild reaction conditions, high yields and application of inexpensive, readily and easily available iodine as catalyst and formation of 2-pyridones as major products are the advantages of the present procedure. In vitro antiproliferative activity of the final synthesized compounds was evaluated with four different human cancer cell lines (Lung adenocarcinoma-A549, Hepatocarcinoma-HepG2, Breast carcinoma-MCF-7 and Ovarian carcinoma-SKOV3) and normal human lung fibroblast cell line (MRC-5). Compounds 2b showed better inhibition against MCF-7, HepG2 and A549 cell lines (IC50 8.00 ± 0.11, 11.93 ± 0.01 and 15.85 ± 0.04 μM, respectively) as compared with doxorubicin and also 2e showed moderate inhibition against MCF-7, HepG2 (IC50 9.32 ± 0.21 and 20.22 ± 0.01 μM, respectively, cell lines, respectively) as compared with doxorubicin. As many clinically used antiproliferative agents induce apoptosis in cancer cells hence, the 2-pyridone analogues were also tested for their ability to induce apoptosis in MCF-7 cells using the caspases-3 and -9 assays. PMID:27036521

  11. Total Synthesis of Enantiopure (+)-γ -Lycorane Using Highly Efficient Pd-Catalyzed Asymmetric Allylic Alkylation

    PubMed Central

    Chapsal, Bruno D.; Ojima, Iwao

    2008-01-01

    Highly efficient short total synthesis of γ -lycorane (>99% ee, 41% overall yield) was achieved by using the asymmetric allylic alkylation in the key step catalyzed by palladium complexes with novel chiral biphenol-based monodentate phosphoramidite ligands. PMID:16562900

  12. Directed Evolution of Stereoselective Hybrid Catalysts

    NASA Astrophysics Data System (ADS)

    Reetz, Manfred T.

    Whereas the directed evolution of stereoselective enzymes provides a useful tool in asymmetric catalysis, generality cannot be claimed because enzymes as catalysts are restricted to a limited set of reaction types. Therefore, a new concept has been proposed, namely directed evolution of hybrid catalysts in which proteins serve as hosts for anchoring ligand/transition metal entities. Accordingly, appropriate genetic mutagenesis methods are applied to the gene of a given protein host, providing after expression a library of mutant proteins. These are purified and a ligand/transition metal anchored site-specifically. Following en masse ee-screening, the best hit is identified, and the corresponding mutant gene is used as a template for another round of mutagenesis, expression, purification, bioconjugation, and screening. This allows for a Darwinian optimization of transition metal catalysts.

  13. Stereoselectivity of phosphotriesterase with paraoxon derivatives: a computational study.

    PubMed

    Zhan, Dongling; Guan, Shanshan; Jin, Hanyong; Han, Weiwei; Wang, Song

    2016-01-01

    The bacterial enzyme phosphotriesterase (PTE) exhibits stereoselectivity toward hydrolysis of chiral substrates with a preference for the Sp enantiomer. In this work, docking analysis and two explicit-solvent molecular dynamics (MD) simulations were performed to characterize and differentiate the structural dynamics of PTE bound to the Sp and Rp paraoxon derivative enantiomers (Rp-1 and Sp-1) hydrolyzed with distinct catalytic efficiencies. Comparative analysis of the molecular trajectories for PTE bound to Rp-1 and Sp-1 suggested that substrate binding induced conformational changes in the loops near the active site. After 100 ns of MD simulation, the Zn β(2+) metal ion formed hexacoordinated- and tetracoordinated geometries in the Sp-1-PTE and Rp-1-PTE ensembles, respectively. Simulation results further showed that the hydrogen bond between Asp301 and His254 occurred with a higher probability after Sp-1 binding to PTE (47.5%) than that after Rp-1 binding (22.2%). These results provide a qualitative and molecular-level explanation for the 10 orders of magnitude increase in the catalytic efficiency of PTE toward the Sp enantiomer of paraoxon. PMID:25929154

  14. Highly Efficient Formal [2+2+2] Strategy for the Rapid Construction of Polycyclic Spiroindolines: A Concise Synthesis of 11-Demethoxy-16-epi-myrtoidine.

    PubMed

    Zhu, Jun; Cheng, Yu-Jing; Kuang, Xiao-Kang; Wang, Lijia; Zheng, Zhong-Bo; Tang, Yong

    2016-08-01

    A novel formal [2+2+2] strategy for the stereoselective elaboration of polycyclic indole alkaloids is described. Upon treatment with the catalyst InCl3 (5 mol %), tryptamine-derived enamides reacted readily with methylene malonate, thus enabling rapid and gram-scale access to versatile tetracyclic spiroindolines with excellent diastereoselectivity (21 examples, up to 95 % yield, up to d.r.>95:5). This strategy provides a concise approach to alkaloids isolated from Strychnos myrtoides, as demonstrated by a short synthesis of 11-demethoxy-16-epi-myrtoidine. PMID:27312730

  15. Chemical Synthesis of the Tumor-Associated Globo H Antigen†

    PubMed Central

    Mandal, Satadru S.; Liao, Guochao; Guo, Zhongwu

    2015-01-01

    A derivative of the tumor-associated globo H antigen, a complex hexasaccharide, was synthesized by a convergent and efficient [3+2+1] strategy using various glycosylation methods. All glycosylation reactions afforded good to excellent yields and outstanding stereoselectivity, including the installation of cis α-linked D-galactose and L-fucose. The longest linear sequence for this synthesis was 11 steps from a galactose derivative 11 to give an overall yield of 2.6%. The synthetic target had a free and reactive amino group at the glycan reducing end, facilitating its conjugation with other molecules for various applications. PMID:26257889

  16. Perylenequinone Natural Products: Total Synthesis of Hypocrellin A

    PubMed Central

    O’Brien, Erin M.; Morgan, Barbara J.; Mulrooney, Carol A.; Carroll, Patrick J.; Kozlowski, Marisa C.

    2009-01-01

    An efficient and stereoselective total synthesis of the perylenequinone natural product hypocrellin A (1) is described. The key features include a potentially biomimetic 1,8-diketone aldol cyclization to set the centrochiral C7,C7’-stereochemistry, bis(trifluoroacetoxy)iodobenzene mediated oxygenation, a palladium-catalyzed decarboxylation, and an enantioselective catalytic oxidative 2-naphthol coupling to establish the biaryl axial chirality. The helical stereochemistry is formed from an axial chiral intermediate and is then utilized in a dynamic stereochemical transfer to dictate the stereochemistry of the C7,C7’-seven membered ring formed during the aldol cyclization. PMID:19894741

  17. 2,2',5,5'-tetramethyl-4,4'-bis(diphenylphoshino)-3,3'-bithiophene: a new, very efficient, easily accessible, chiral biheteroaromatic ligand for homogeneous stereoselective catalysis

    PubMed

    Benincori; Cesarotti; Piccolo; Sannicolo

    2000-04-01

    The four-step straightforward synthesis of enantiopure (+)- and (-)-2,2',5,5'-tetramethyl-4,4'-bis-(diphenylphoshino)-3,3'-bithiophene (tetraMe-BITIOP), a new C2-symmetry chelating ligand for transition metals, is described, starting from 2,5-dimethylthiophene. The complexes of this electron-rich diphosphine with Ru(II) and Rh(I) were used as catalysts in some homogeneous hydrogenation reactions of prostereogenic carbonyl functions of alpha- and beta-ketoesters, of prostereogenic carbon-carbon double bonds of substituted acrylic acids, and of N-acetylenamino acids. The enantiomeric excesses were found to be excellent in all the experiments and comparable with the best results reported in the literature for the same reactions, carried out under similar experimental conditions, with the metal complexes of the most popular chiral diphosphine ligands as catalysts. PMID:10774024

  18. An enzyme-encapsulated microreactor for efficient theanine synthesis.

    PubMed

    Matsuura, Shun-ichi; Yokoyama, Takuji; Ishii, Ryo; Itoh, Tetsuji; Tomon, Emiko; Hamakawa, Satoshi; Tsunoda, Tatsuo; Mizukami, Fujio; Nanbu, Hironobu; Hanaoka, Taka-aki

    2012-07-18

    A flow-type microreactor containing glutaminase-mesoporous silica composites with 10.6 nm pore diameter (TMPS10.6) was developed for the continuous synthesis of theanine, a unique amino acid. High enzymatic activity was exhibited by the local control of the reaction temperature. PMID:22674037

  19. Stereoselective reaction of 2-carboxythioesters-1,3-dithiane with nitroalkenes: an organocatalytic strategy for the asymmetric addition of a glyoxylate anion equivalent.

    PubMed

    Massolo, Elisabetta; Benaglia, Maurizio; Genoni, Andrea; Annunziata, Rita; Celentano, Giuseppe; Gaggero, Nicoletta

    2015-05-28

    An efficient organocatalytic methodology has been developed to perform the stereoselective addition of 2-carboxythioesters-1,3-dithiane to nitroalkenes. Under mild reaction conditions γ-nitro-β-aryl-α-keto esters with up to 92% ee were obtained, realizing a formal catalytic stereoselective conjugate addition of the glyoxylate anion synthon. The reaction products are versatile starting materials for further synthetic transformations; for example, the simultaneous reduction of the nitro group and removal of the dithiane ring was accomplished, allowing the preparation of a GABAB receptor agonist baclofen. PMID:25883074

  20. Stereoselective Rh-Catalyzed Hydrogenative Desymmetrization of Achiral Substituted 1,4-Dienes.

    PubMed

    Fernández-Pérez, Héctor; Lao, Joan R; Vidal-Ferran, Anton

    2016-06-17

    Highly efficient catalytic stereoselective hydrogenative desymmetrization reactions mediated by rhodium complexes derived from enantiopure phosphine-phosphite (P-OP) ligands are described. The highest performing ligand, which contains a TADDOL-derived phosphite fragment [TADDOL = (2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(diphenylmethanol)], presented excellent catalytic properties for the desymmetrization of a set of achiral 1,4-dienes, providing access to the selective formation of a variety of enantioenriched secondary and tertiary alcohols (six examples, up to 92% ee). PMID:27230728

  1. Highly Chemo-, Regio-, and Stereoselective Cobalt-Catalyzed Markovnikov Hydrosilylation of Alkynes.

    PubMed

    Guo, Jun; Lu, Zhan

    2016-08-26

    A highly chemo-, regio- and stereoselective cobalt-catalyzed Markovnikov hydrosilylation of alkynes was developed. Various functionalized groups, such as halides, free alcohols, free aniline, ketones, esters, amides, and nitriles are tolerated, which may lead to further applications and late-stage derivatizations. To date, this is the most efficient cobalt catalytic system (TOF=65 520 h(-1) ; TOF=turnover frequency) for hydrosilylation of alkynes. The Hiyama-Denmark cross-coupling reactions of vinylsilanes with aryl iodides underwent smoothly to afford 1,1-diarylethenes. A unique regioselectivity-controllable hydrosilylation/hydroboration reaction of alkynes was also described. PMID:27440515

  2. Iridium/Copper Co-catalyzed Anti-Stereoselective Ring Opening of Oxabenzonorbornadienes with Grignard Reagents.

    PubMed

    Cheng, Guo; Yang, Wen; Li, Yue; Yang, Dingqiao

    2016-09-01

    Cooperative catalysis has been widely considered as one of the most powerful strategies to improve synthetic efficiency. A new iridium/copper cocatalyst was developed for the ring-opening reaction of oxabenzonorbornadienes with a wide variety of Grignard reagents, which afforded the corresponding anti-2-substituted 1,2-dihydronaphthalen-1-ols in high yields (up to 99% yield) under mild conditions. The effects of catalyst loading, Lewis acid, Grignard reagent loading, and reaction temperature on the yield were investigated. To the best of our knowledge, it represents the first example of ring-opening reactions of oxabicyclic alkenes with Grignard reagent nucleophiles in a trans-stereoselective manner. PMID:27455165

  3. Continuous-flow stereoselective organocatalyzed Diels-Alder reactions in a chiral catalytic "homemade" HPLC column.

    PubMed

    Chiroli, Valerio; Benaglia, Maurizio; Cozzi, Franco; Puglisi, Alessandra; Annunziata, Rita; Celentano, Giuseppe

    2013-07-19

    Continuous-flow organocatalyzed Diels-Alder reactions have been performed with excellent enantioselectivity for the first time in a chiral "homemade" HPLC column, packed with silica on which a MacMillan catalyst has been supported by a straightforward immobilization procedure. The versatility of the system was also proven by running with the same column continuous-flow stereoselective reactions with three different substrates, showing that the catalytic reactor may efficiently work in continuo for more than 150 h; the regeneration of the HPLC column was also demonstrated, allowing to further extend the activity of the reactor to more than 300 operating hours. PMID:23808663

  4. A Novel Implementation of Efficient Algorithms for Quantum Circuit Synthesis

    NASA Astrophysics Data System (ADS)

    Zeller, Luke

    In this project, we design and develop a computer program to effectively approximate arbitrary quantum gates using the discrete set of Clifford Gates together with the T gate (π/8 gate). Employing recent results from Mosca et. al. and Giles and Selinger, we implement a decomposition scheme that outputs a sequence of Clifford, T, and Tt gates that approximate the input to within a specified error range ɛ. Specifically, the given gate is first rounded to an element of Z[1/2, i] with a precision determined by ɛ, and then exact synthesis is employed to produce the resulting gate. It is known that this procedure is optimal in approximating an arbitrary single qubit gate. Our program, written in Matlab and Python, can complete both approximate and exact synthesis of qubits. It can be used to assist in the experimental implementation of an arbitrary fault-tolerant single qubit gate, for which direct implementation isn't feasible.

  5. Remarkable beta-selectivity in the synthesis of beta-1-C-arylglucosides: stereoselective reduction of acetyl-protected methyl 1-C-arylglucosides without acetoxy-group participation.

    PubMed

    Deshpande, Prashant P; Ellsworth, Bruce A; Buono, Frederic G; Pullockaran, Annie; Singh, Janak; Kissick, Thomas P; Huang, Ming-H; Lobinger, Hildegard; Denzel, Theodor; Mueller, Richard H

    2007-12-01

    An efficient and practical process to generate beta-C-arylglucoside derivatives was achieved. The process described involves Lewis acid mediated ionic reduction of a peracetylated 1-C-aryl methyl glucoside derived from the addition of an aryl-Li to selectively protected delta-D-gluconolactone. The reduction of the 2-acetoxy-1-C-oxacarbenium ion intermediates proceeds with a high degree of selectivity to give beta-C-arylglucosides without 2-acetoxy group participation. Furthermore, during the reduction process we also identified an unprecedented critical role of water. By changing from the usual benzyl ether protecting groups because of cost and chemical compatibility concerns, the new process is made additionally efficient and highly selective. PMID:17997568

  6. Odorless, One-Pot Regio- and Stereoselective Iodothiolation of Alkynes with Sodium Arenesulfinates under Metal-Free Conditions in Water.

    PubMed

    Lin, Ya-mei; Lu, Guo-ping; Cai, Chun; Yi, Wen-bin

    2015-07-01

    A newly developed regio- and stereoselective radical addition of alkyne under metal-free conidtions has been disclosed. This chemistry, in which odorless sodium arenesulfinates in place of thiols are used as the sulfur reagent, provides an efficient, one-pot approach for the generation of β-iodoalkenyl sulfides, which can be easily further functionalized to derive various alkenes and alkynyl sulfides rendering this methodology attractive to both synthetic and medicinal chemistry. PMID:26084011

  7. Synergy, compatibility, and innovation: merging Lewis acids with stereoselective enamine catalysis.

    PubMed

    Gualandi, Andrea; Mengozzi, Luca; Wilson, Claire M; Cozzi, Pier Giorgio

    2014-04-01

    In recent years there has been an accelerated rate of development in the field of organocatalysis, with asymmetric organocatalysis now reaching full maturity. The invention of new organocatalytic reactions and the exploration of new concepts now appear in tandem with the application of organocatalytic techniques in the synthesis of natural products and active pharmaceutical ingredients (APIs). After a "golden rush" in organocatalysis, researchers are now starting to combine different methods, thereby taking advantage of the significant benefits of synergy. Metals are used in combination with organocatalytic processes, thus reaching complexity that is found in nature, where enzymes take advantage of the presence of certain metals to increase the arsenal of organic transformations available. In this Focus review, we illustrate the possibility of a "happy marriage" between Lewis acids and organocatalytic stereoselective processes. Questions have been raised about the combination of Lewis acids and organocatalysis owing to the presence of water and/or strong bases in these processes. Some Lewis acids have been shown to be compatible with organocatalysis and concepts relating to their use will be illustrated herein. To summarize the fruitful use of Lewis acids in stereoselective organocatalytic processes, we will draw attention to the advantages and selectivity achieved using this method. PMID:24677815

  8. Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists

    SciTech Connect

    Eltze, M.; Boer, R.; Sanders, K.H.; Boss, H.; Ulrich, W.R.; Flockerzi, D. )

    1990-01-01

    The biological activity of the (+)-S- and (-)-R-enantiomers of niguldipine, of the (-)-S- and (+)-R-enantiomers of felodipine and nitrendipine, and of rac-nisoldipine and rac-nimodipine was investigated in vitro and in vivo. Inhibition of coronary vasoconstriction due to the thromboxane A2 (TxA2)-mimetic U-46619 in guinea pig Langendorff hearts, displacement of (+)-({sup 3}H)isradipine from calcium channel binding sites of guinea pig skeletal muscle T-tubule membranes, and blood pressure reduction in spontaneously hypertensive rats were determined. The enantiomers were obtained by stereoselective synthesis. Cross-contamination was less than 0.5% for both S- and R-enantiomers of niguldipine and nitrendipine and less than 1% for those of felodipine. From the doses necessary for a 50% inhibition of coronary vasoconstriction, stereoselectivity ratios for (+)-(S)-/(-)-(R)-niguldipine, (-)-(S)-/(+)-(R)-felodipine, and (-)-(S)-/(+)-(R)-nitrendipine of 28, 13, and 7, respectively, were calculated. The potency ratio rac-nisoldipine/rac-nimodipine was 3.5. Ratios obtained from binding experiments and antihypertensive activity were (+)-(S)-/(-)-(R)-niguldipine = 45 and 35, (-)-(S)-/(+)-(R)-felodipine = 12 and 13, (-)-(S)-/(+)-(R)-nitrendipine = 8 and 8, and rac-nisoldipine/rac-nimodipine = 8 and 7, respectively. Highly significant correlations were found between the in vitro potency of the substances to prevent U-46619-induced coronary vasoconstriction and their affinity for calcium channel binding sites as well as their antihypertensive activity.

  9. Assimilation efficiencies of chemical contaminants in aquatic invertebrates: A synthesis

    SciTech Connect

    Wang, W.X.; Fisher, N.S.

    1999-09-01

    Assimilation efficiencies of contaminants from ingested food are critical for understanding chemical accumulation and trophic transfer in aquatic invertebrates. Assimilation efficiency is a first-order physiological parameter that can be used to systematically compare the bioavailability of different contaminants from different foods. The various techniques used to measure contaminant assimilation efficiencies are reviewed. Pulse-chase feeding techniques and the application of gamma-emitting radiotracers have been invaluable in measuring metal assimilation efficiencies in aquatic animals. Uniform radiolabeling of food is required to measure assimilation, but this can be difficult when sediments are the food source. Biological factors that influence contaminant assimilation include food quantity and quality, partitioning of contaminants in the food particles, and digestive physiology of the animals. Other factors influencing assimilation include the behavior of the chemical within the animal's gut and its associations with different geochemical fractions of food particles. Assimilation efficiency is a critical parameter to determine (and to make predictions of) bioaccumulation of chemicals from dietary exposure. Robust estimates of assimilation efficiency coupled with estimates of aqueous uptake can be used to determine the relative importance of aqueous and dietary exposures. For bioaccumulation of metals from sediments, additional studies are required to test whether metals bound to the acid-volatile sulfide fraction of sediments can be available to benthic deposit-feeding inverterbrates. Most assimilation efficiency studies have focused on chemical transfer in organisms at the bottom of the food chain; additional studies are required to examine chemical transfer at higher trophic levels.

  10. Origins of Stereoselectivity in the trans-Diels-Alder Paradigm

    PubMed Central

    Paton, Robert S.; Mackey, Joel L.; Kim, Woo Han; Lee, Jun Hee; Danishefsky, Samuel J.; Houk, K. N.

    2010-01-01

    The regioselectivity and stereoselectivity aspects of the Diels-Alder/radical hydrodenitration reaction sequence leading to trans-fused ring systems have been investigated with density functional calculations. A continuum of transition structures representing Diels-Alder and hetero-Diels-Alder cycloadditions as well as a sigmatropic rearrangement have been located, and they all lie very close in energy on the potential energy surface. All three pathways are found to be important in the formation of the Diels-Alder adduct. Reported regioselectivities are reproduced by the calculations. The stereoselectivity of radical hydrodenitration of the cis-Diels-Alder adduct is found to be related to the relative conformational stabilities of bicyclic radical intermediates. Overall, the computations provide understanding of the regioselectivities and stereoselectivities of the trans-Diels-Alder paradigm. PMID:20557046

  11. Efficiency, error and yield in light-directed maskless synthesis of DNA microarrays

    PubMed Central

    2011-01-01

    Background Light-directed in situ synthesis of DNA microarrays using computer-controlled projection from a digital micromirror device--maskless array synthesis (MAS)--has proved to be successful at both commercial and laboratory scales. The chemical synthetic cycle in MAS is quite similar to that of conventional solid-phase synthesis of oligonucleotides, but the complexity of microarrays and unique synthesis kinetics on the glass substrate require a careful tuning of parameters and unique modifications to the synthesis cycle to obtain optimal deprotection and phosphoramidite coupling. In addition, unintended deprotection due to scattering and diffraction introduce insertion errors that contribute significantly to the overall error rate. Results Stepwise phosphoramidite coupling yields have been greatly improved and are now comparable to those obtained in solid phase synthesis of oligonucleotides. Extended chemical exposure in the synthesis of complex, long oligonucleotide arrays result in lower--but still high--final average yields which approach 99%. The new synthesis chemistry includes elimination of the standard oxidation until the final step, and improved coupling and light deprotection. Coupling Insertions due to stray light are the limiting factor in sequence quality for oligonucleotide synthesis for gene assembly. Diffraction and local flare are by far the largest contributors to loss of optical contrast. Conclusions Maskless array synthesis is an efficient and versatile method for synthesizing high density arrays of long oligonucleotides for hybridization- and other molecular binding-based experiments. For applications requiring high sequence purity, such as gene assembly, diffraction and flare remain significant obstacles, but can be significantly reduced with straightforward experimental strategies. PMID:22152062

  12. Stereoselective cyclotetramerization of a 3-(Hydroxymethyl)salicylaldehyde

    PubMed

    Butler; Brown; Boger; Ferfolia; Fitzgibbons; Jongeling; Kelleher; Malec; Malerich; Weltner

    2000-12-28

    Both 3-(hydroxymethyl)-5-methylsalicylaldehyde and its acetonide condense in the presence of hydrogen chloride in ether to form macrocyclic S(4)-symmetric tetraacetal 2. The reaction is completely oligo- and stereoselective, forming only the tetramer and only the achiral (R,S,R,S)-stereoisomer. Acid-catalyzed equilibration studies and molecular mechanics calculations indicate that the stereoselectivity is thermodynamic in origin. In the crystal the saddle-shaped molecules of 2 form coaxial stacks reminiscent of the packing of Pringles potato chips. PMID:11150180

  13. Efficient synthesis of triarylamine-based dyes for p-type dye-sensitized solar cells

    PubMed Central

    Wild, Martin; Griebel, Jan; Hajduk, Anna; Friedrich, Dirk; Stark, Annegret; Abel, Bernd; Siefermann, Katrin R.

    2016-01-01

    The class of triarylamine-based dyes has proven great potential as efficient light absorbers in inverse (p-type) dye sensitized solar cells (DSSCs). However, detailed investigation and further improvement of p-type DSSCs is strongly hindered by the fact that available synthesis routes of triarylamine-based dyes are inefficient and particularly demanding with regard to time and costs. Here, we report on an efficient synthesis strategy for triarylamine-based dyes for p-type DSSCs. A protocol for the synthesis of the dye-precursor (4-(bis(4-bromophenyl)amino)benzoic acid) is presented along with its X-ray crystal structure. The dye precursor is obtained from the commercially available 4(diphenylamino)benzaldehyde in a yield of 87% and serves as a starting point for the synthesis of various triarylamine-based dyes. Starting from the precursor we further describe a synthesis protocol for the dye 4-{bis[4′-(2,2-dicyanovinyl)-[1,1′-biphenyl]-4-yl]amino}benzoic acid (also known as dye P4) in a yield of 74%. All synthesis steps are characterized by high yields and high purities without the need for laborious purification steps and thus fulfill essential requirements for scale-up. PMID:27196877

  14. Efficient synthesis of triarylamine-based dyes for p-type dye-sensitized solar cells.

    PubMed

    Wild, Martin; Griebel, Jan; Hajduk, Anna; Friedrich, Dirk; Stark, Annegret; Abel, Bernd; Siefermann, Katrin R

    2016-01-01

    The class of triarylamine-based dyes has proven great potential as efficient light absorbers in inverse (p-type) dye sensitized solar cells (DSSCs). However, detailed investigation and further improvement of p-type DSSCs is strongly hindered by the fact that available synthesis routes of triarylamine-based dyes are inefficient and particularly demanding with regard to time and costs. Here, we report on an efficient synthesis strategy for triarylamine-based dyes for p-type DSSCs. A protocol for the synthesis of the dye-precursor (4-(bis(4-bromophenyl)amino)benzoic acid) is presented along with its X-ray crystal structure. The dye precursor is obtained from the commercially available 4(diphenylamino)benzaldehyde in a yield of 87% and serves as a starting point for the synthesis of various triarylamine-based dyes. Starting from the precursor we further describe a synthesis protocol for the dye 4-{bis[4'-(2,2-dicyanovinyl)-[1,1'-biphenyl]-4-yl]amino}benzoic acid (also known as dye P4) in a yield of 74%. All synthesis steps are characterized by high yields and high purities without the need for laborious purification steps and thus fulfill essential requirements for scale-up. PMID:27196877

  15. Efficient synthesis of triarylamine-based dyes for p-type dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Wild, Martin; Griebel, Jan; Hajduk, Anna; Friedrich, Dirk; Stark, Annegret; Abel, Bernd; Siefermann, Katrin R.

    2016-05-01

    The class of triarylamine-based dyes has proven great potential as efficient light absorbers in inverse (p-type) dye sensitized solar cells (DSSCs). However, detailed investigation and further improvement of p-type DSSCs is strongly hindered by the fact that available synthesis routes of triarylamine-based dyes are inefficient and particularly demanding with regard to time and costs. Here, we report on an efficient synthesis strategy for triarylamine-based dyes for p-type DSSCs. A protocol for the synthesis of the dye-precursor (4-(bis(4-bromophenyl)amino)benzoic acid) is presented along with its X-ray crystal structure. The dye precursor is obtained from the commercially available 4(diphenylamino)benzaldehyde in a yield of 87% and serves as a starting point for the synthesis of various triarylamine-based dyes. Starting from the precursor we further describe a synthesis protocol for the dye 4-{bis[4‧-(2,2-dicyanovinyl)-[1,1‧-biphenyl]-4-yl]amino}benzoic acid (also known as dye P4) in a yield of 74%. All synthesis steps are characterized by high yields and high purities without the need for laborious purification steps and thus fulfill essential requirements for scale-up.

  16. Stereoselective fungal metabolism of methylated anthracenes.

    PubMed Central

    Cerniglia, C E; Campbell, W L; Fu, P P; Freeman, J P; Evans, F E

    1990-01-01

    The metabolism of 9-methylanthracene (9-MA), 9-hydroxymethylanthracene (9-OHMA), and 9,10-dimethylanthracene (9,10-DMA) by the fungus Cunninghamella elegans ATCC 36112 is described. The metabolites were isolated by high-performance liquid chromatography and characterized by UV-visible, mass, and 1H nuclear magnetic resonance spectral techniques. The compounds 9-MA and 9,10-DMA were metabolized by two pathways, one involving initial hydroxylation of the methyl group(s) and the other involving epoxidation of the 1,2- and 3,4- aromatic double bond positions, followed by enzymatic hydration to form hydroxymethyl trans-dihydrodiols. For 9-MA metabolism, the major metabolites identified were trans-1,2-dihydro-1,2-dihydroxy and trans-3,4-dihydro-3,4-dihydroxy derivatives of 9-MA and 9-OHMA. 9-OHMA was also metabolized to trans-1,2- and 3,4-dihydrodiol derivatives. The absolute configuration and optical purity were determined for each of the trans-dihydrodiols formed by fungal metabolism and compared with previously published circular dichroism spectral data obtained from rat liver microsomal metabolism of 9-MA, 9-OHMA, and 9,10-DMA. Circular dichroism spectral analysis revealed that the major enantiomer for each dihydrodiol was predominantly in the S,S configuration, in contrast to the predominantly R,R configuration of the trans-dihydrodiol formed by mammalian enzyme systems. These results indicate that C. elegans metabolizes methylated anthracenes in a highly stereoselective manner that is different from that reported for rat liver microsomes. PMID:2317041

  17. Stereoselective construction of the 5-hydroxy diazabicyclo[4.3.1]decane-2-one scaffold, a privileged motif for FK506-binding proteins.

    PubMed

    Bischoff, Matthias; Sippel, Claudia; Bracher, Andreas; Hausch, Felix

    2014-10-17

    A stereoselective synthesis of a derivatized bicyclic [4.3.1]decane scaffold based on an acyclic precursor is described. The key steps involve a Pd-catalyzed sp(3)-sp(2) Negishi-coupling, an asymmetric Shi epoxidation, and an intramolecular epoxide opening. Representative derivatives of this novel scaffold were synthesized and found to be potent inhibitors of the psychiatric risk factor FKBP51, which bound to FKBP51 with the intended molecular binding mode. PMID:25286062

  18. Asymmetric Conjugate Addition of Benzofuran-2-ones to Alkyl 2-Phthalimidoacrylates: Modeling Structure-Stereoselectivity Relationships with Steric and Electronic Parameters.

    PubMed

    Yang, Chen; Zhang, En-Ge; Li, Xin; Cheng, Jin-Pei

    2016-05-23

    A highly predictive model to correlate the steric and electronic parameters of tertiary amine thiourea catalysts with the stereoselectivity of Michael reactions of 3-substituted benzofuranones and alkyl 2-phthalimidoacrylates is described. As predicted, new 3,5-bis(trifluoromethyl)benzyl- and methyl-substituted tertiary amine thioureas turned out to be highly suitable catalysts for this reaction and enabled the synthesis of enantioenriched α-amino acid derivatives with 1,3-nonadjacent stereogenic centers. PMID:27080558

  19. Assessment of the stereoselective metabolism of methaqualone in man by capillary electrophoresis.

    PubMed

    Prost, Francine; Thormann, Wolfgang

    2003-08-01

    Methaqualone (MQ) and its hydroxylated metabolites are quinazoline derivatives that exhibit atropisomerism. As a continuation of our previous work with these compounds (Electrophoresis 2001, 22, 3270-3280), chiral capillary zone electrophoresis with hydroxypropyl-beta-cyclodextrin as buffer additive and multiwavelength absorbance detection is shown to be an effective tool to provide insight into the stereoselectivity of the MQ metabolism. The five major monohydroxy MQ metabolites formed during biotransformation do not show enantiomerization at temperatures up to 85 degrees C. Enzymatic and acidic hydrolysis of urines that were collected after concomitant administration of 250 mg of MQ and 25 mg diphenhydramine (DH) chloride are both shown to provide stereoselective metabolic patterns with 4'-hydroxymethaqualone, the major urinary metabolite, being excreted almost exclusively as a single enantiomer. A stereoselectivity in the formation of 2'-hydroxymethaqualone and 2-hydroxymethaqualone was also observed in vitro using human liver microsomes and preparations containing the cytochrome P450 enzyme (CYP) CYP3A4 only. The presence of DH during incubation with human liver microsomes did not reveal a difference in the metabolic pattern obtained. Furthermore, CYP2D6 and CYP2C19 do not significantly contribute to the metabolism of MQ. This was independently observed in vitro and via analysis of urines of individuals that are either efficient metabolizer phenotypes or poor metabolizer phenotypes for the two polymorphic enzymes. Although interindividual differences in the monitored metabolic patterns were noted, no marked difference could be related to a CYP2D6 or CYP2C19 polymorphism. PMID:12900872

  20. Total Synthesis of (-)-Daphenylline.

    PubMed

    Yamada, Ryosuke; Adachi, Yohei; Yokoshima, Satoshi; Fukuyama, Tohru

    2016-05-10

    Total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid, was achieved. Construction of the tricyclic DEF ring system was initiated by asymmetric Negishi coupling followed by an intramolecular Friedel-Crafts reaction. Installation of a side chain onto the tricyclic core was carried out through Sonogashira coupling, stereocontrolled Claisen rearrangement by taking advantage of the characteristic conformation of the tricyclic DEF core, and the stereoselective alkylation of a lactone. After the introduction of a glycine unit, the ABC ring system was stereoselectively constructed through intramolecular cycloaddition of the cyclic azomethine ylide. PMID:27062676

  1. Efficient one-pot synthesis of 1-arylcycloprop-2-ene-1-carboxamides.

    PubMed

    Edwards, Andrew; Rubin, Michael

    2016-03-14

    An expeditious and cost-efficient method for synthesis of 1-arylcycloprop-2-ene-1-carboxamides was developed. This one-pot protocol involving coupling of amines with acyl chlorides, generated upon treatment of cyclopenylcarboxylic acids with oxalyl chloride, is applicable for the preparation of sensitive products with a reactive, unsubstituted strained double bond. PMID:26864495

  2. ACCESS-2: Approximation Concepts Code for Efficient Structural Synthesis, user's guide

    NASA Technical Reports Server (NTRS)

    Miura, H.; Schmit, L. A., Jr.

    1978-01-01

    A user's guide is presented for the ACCESS-2 computer program. ACCESS-2 is a research oriented program which implements a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and general mathematical programming algorithms are applied in the design optimization procedure.

  3. Domino Strategy for the Stereoselective Construction of Angularly Fused Tricyclic Ethers.

    PubMed

    Reddy, B V Subba; Medaboina, Durgaprasad; Reddy, S Gopal; Reddy, V Hanuman; Singarapu, Kiran Kumar; Sridhar, Balasubramanian

    2015-12-18

    A stereoselective synthesis of decahydrofuro[3,2-d]isochromene derivatives has been achieved by the condensation of 2-cyclohexenylbutane-1,4-diol with aldehydes in the presence of a stochiometric amount of BF3·OEt2 in dichloromethane at -78 °C. Similarly, the condensation of 2-cyclopentenylbutan-1,4-diol with aldehydes provides the corresponding octahydro-2H-cyclopenta[c]furo[2,3-d]pyran derivatives in good yields with high diastereoselectivity. It is an elegant strategy for the quick construction of tricyclic architectures with four contiguous stereogenic centers in a single step. These tricyclic frameworks are the integral part of numerous natural products. PMID:26562722

  4. Stereoselective formation of a 2 prime (3 prime)- aminoacyl ester of a nucleotide

    NASA Technical Reports Server (NTRS)

    Weber, A. L.

    1986-01-01

    Reaction of DL-series and adenosine-5-phosphorimidazolide in the presence of adenosine-5'-(0-methylphosphate) and imidazole resulted in the stereoselective synthesis of the aminoacyl nucleotide ester, 2'(3')-0-seryl-adenosine-5'-(0-methylphosphate). The enantiomeric excess of D-serine incorporated into 2'(3')-0-seryl-adenosine-5'-(0-methylphosphate) was about 9%. Adenylyl-(5->N)-serine and an unknown product also incorporated an excess of D-serine, however, seryl-serine showed an excess of L-serine. The relationship of these results to the origin of the biological pairing of L-amino acids and nucleotides containing D-ribose is discussed.

  5. Improvement of efficiency in the enzymatic synthesis of lactulose palmitate.

    PubMed

    Bernal, Claudia; Illanes, Andres; Wilson, Lorena

    2015-04-15

    Sugar esters are considered as surfactants due to its amphiphilic balance that can lower the surface tension in oil/water mixtures. Enzymatic syntheses of these compounds are interesting both from economic and environmental considerations. A study was carried out to evaluate the effect of four solvents, temperature, substrate molar ratio, biocatalyst source, and immobilization methodology on the yield and specific productivity of lactulose palmitate monoester synthesis. Lipases from Pseudomonas stutzeri (PsL) and Alcaligenes sp. (AsL), immobilized in porous silica functionalized with octyl groups (adsorption immobilization, OS) and with glyoxyl-octyl groups (both adsorption and covalent immobilization, OGS), were used. The highest lactulose palmitate yields were obtained at 47 °C in acetone, for all biocatalysts, while the best lactulose:palmitic acid molar ratio differed according to the immobilization methodology, being 1:1 for AsL-OGS biocatalyst (20.7 ± 3%) and 1:3 for the others (30-50%). PMID:25797166

  6. An efficient prebiotic synthesis of cytosine and uracil

    NASA Astrophysics Data System (ADS)

    Robertson, Michael P.; Miller, Stanley L.

    1995-06-01

    IN contrast to the purines1 3, the routes that have been proposed for the prebiotic synthesis of pyrimidines from simple precursors give only low yields. Cytosine can be synthesized from cyano-acetylene and cyanate4,5; the former precursor is produced from a spark discharge in a CH4/N2 mixture4,5 and is an abundant interstellar molecule6. But this reaction requires relatively high concentrations of cyanate (>0.1 M), which are unlikely to occur in aqueous media as cyanate is hydrolysed rapidly to CO2 and NH3. An alternative route that has been explored7 is the reaction of cyanoacetaldehyde (formed by hydrolysis of cyanoacetylene8) with urea. But at low concentrations of urea, this reaction produces no detectable quantities of cytosine7. Here we show that in concentrated urea solution-such as might have been found in an evaporating lagoon or in pools on drying beaches on the early Earth-cyanoacetaldehyde reacts to form cytosine in yields of 30-50%, from which uracil can be formed by hydrolysis. These reactions provide a plausible route to the pyrimidine bases required in the RNA world9.

  7. Efficient synthesis of probabilistic quantum circuits with fallback

    NASA Astrophysics Data System (ADS)

    Bocharov, Alex; Roetteler, Martin; Svore, Krysta M.

    2015-05-01

    Repeat-until-success (RUS) circuits can approximate a given single-qubit unitary with an expected number of T gates of about 1/3 of what is required by optimal, deterministic, ancilla-free decompositions over the Clifford + T gate set. In this work, we introduce a more general and conceptually simpler circuit decomposition method that allows for synthesis into protocols that probabilistically implement quantum circuits over several universal gate sets including, but not restricted to, the Clifford + T gate set. The protocol, which we call probabilistic quantum circuits with fallback (PQF), implements a walk on a discrete Markov chain in which the target unitary is an absorbing state and in which transitions are induced by multiqubit unitaries followed by measurements. In contrast to RUS protocols, the presented PQF protocols are guaranteed to terminate after a finite number of steps. Specifically, we apply our method to the Clifford + T , Clifford + V , and Clifford + π /12 gate sets to achieve decompositions with expected gate counts of logb(1 /ɛ ) +O {ln[ln(1 /ɛ ) ] } , where b is a quantity related to the expansion property of the underlying universal gate set.

  8. An efficient prebiotic synthesis of cytosine and uracil

    NASA Technical Reports Server (NTRS)

    Robertson, M. P.; Miller, S. L.

    1995-01-01

    In contrast to the purines, the routes that have been proposed for the prebiotic synthesis of pyrimidines from simple precursors give only low yields. Cytosine can be synthesized from cyanoacetylene and cyanate; the former precursor is produced from a spark discharge in a CH4/N2 mixture and is an abundant interstellar molecule. But this reaction requires relatively high concentrations of cyanate (> 0.1 M), which are unlikely to occur in aqueous media as cyanate is hydrolysed rapidly to CO2 and NH3. An alternative route that has been explored is the reaction of cyanoacetaldehyde (formed by hydrolysis of cyanoacetylene) with urea. But at low concentrations of urea, this reaction produces no detectable quantities of cytosine. Here we show that in concentrated urea solution--such as might have been found in an evaporating lagoon or in pools on drying beaches on the early Earth--cyanoacetaldehyde reacts to form cytosine in yields of 30-50%, from which uracil can be formed by hydrolysis. These reactions provide a plausible route to the pyrimidine bases required in the RNA world.

  9. Efficient synthesis of Au99(SR)42 nanoclusters

    NASA Astrophysics Data System (ADS)

    Liu, Chao; Lin, Jizhi; Shi, Yangwei; Li, Gao

    2015-03-01

    We report a new synthetic protocol of Au99(SPh)42 nanoclusters with moderate efficiency (~15% yield based on HAuCl4), via a combination of the ligand-exchange and ``size-focusing'' processes. The purity of the as-prepared gold nanoclusters is characterized by matrix-assisted laser desorption ionization mass spectrometry and size exclusion chromatography.We report a new synthetic protocol of Au99(SPh)42 nanoclusters with moderate efficiency (~15% yield based on HAuCl4), via a combination of the ligand-exchange and ``size-focusing'' processes. The purity of the as-prepared gold nanoclusters is characterized by matrix-assisted laser desorption ionization mass spectrometry and size exclusion chromatography. Electronic supplementary information (ESI) available: Experimental section: the synthetic procedure of the Au99(SPh)42 nanoclusters and characterization of the Au cluster. See DOI: 10.1039/c5nr00543d

  10. Efficient Synthesis of Topologically Linked Three-Ring DNA Catenanes.

    PubMed

    Li, Qi; Wu, Guangqi; Wu, Wei; Liang, Xingguo

    2016-06-16

    Topologically controlled DNA catenanes are promising elements for the construction of molecular machines but present a significant effort in DNA nanotechnology. We report an efficient approach for preparing linear three-ring catenanes (L3C) composed of single-stranded DNA. The linking number was strictly controlled by using short complementary regions (6 nt) between each two DNA rings. High efficiency of forming three-ring catenanes (yield as high as 63 %) was obtained by using an 80 nt oligonucleotide as the scaffold to draw close the three pre-rings for hybridization between short complementary DNA. After assembly, three pre-rings were closed by DNA ligation using three 12 nt oligonucleotides as splints to form interlocked three-ring catenanes. L3C nanostructures were imaged in air by AFM: the catenane exhibited a smooth circular shape and was arranged in a line with well-defined structure, as expected. PMID:27214092

  11. Isomerizing ethenolysis as an efficient strategy for styrene synthesis.

    PubMed

    Baader, Sabrina; Ohlmann, Dominik M; Gooßen, Lukas J

    2013-07-22

    A shrinking chain: A bimetallic system consisting of [{Pd(μ-Br)(tBu3P)}2] and a ruthenium metathesis catalyst has been found to efficiently promote the cross-metathesis between substituted alkenes and ethylene, while continuously migrating the double bond along the alkenyl chain (see scheme). When alkenylarenes, such as the natural products eugenol, safrol, or estragol, were treated with this catalyst under an ethylene atmosphere, they were cleanly converted into the corresponding styrenes and propylene gas. PMID:23776109

  12. High stereoselectivity on low temperature Diels-Alder reactions

    PubMed Central

    da Silva Filho, Luiz Carlos; Lacerda Júnior, Valdemar; Constantino, Mauricio Gomes; da Silva, Gil Valdo José; Invernize, Paulo Roberto

    2005-01-01

    We have found that some of the usually poor dienophiles (2-cycloenones) can undergo Diels-Alder reaction at -78°C with unusually high stereoselectivity in the presence of niobium pentachloride as a Lewis acid catalyst. A remarkable difference in reaction rates for unsubstituted and α- or β-methyl substituted 2-cycloenones was also observed. PMID:16542029

  13. High stereoselectivity on low temperature Diels-Alder reactions.

    PubMed

    da Silva Filho, Luiz Carlos; Lacerda Júnior, Valdemar; Constantino, Mauricio Gomes; da Silva, Gil Valdo José; Invernize, Paulo Roberto

    2005-01-01

    We have found that some of the usually poor dienophiles (2-cycloenones) can undergo Diels-Alder reaction at -78 degrees C with unusually high stereoselectivity in the presence of niobium pentachloride as a Lewis acid catalyst. A remarkable difference in reaction rates for unsubstituted and alpha- or beta-methyl substituted 2-cycloenones was also observed. PMID:16542029

  14. An Efficient, Optimized Synthesis of Fentanyl and Related Analogs

    PubMed Central

    Valdez, Carlos A.; Leif, Roald N.; Mayer, Brian P.

    2014-01-01

    The alternate and optimized syntheses of the parent opioid fentanyl and its analogs are described. The routes presented exhibit high-yielding transformations leading to these powerful analgesics after optimization studies were carried out for each synthetic step. The general three-step strategy produced a panel of four fentanyls in excellent yields (73–78%) along with their more commonly encountered hydrochloride and citric acid salts. The following strategy offers the opportunity for the gram-scale, efficient production of this interesting class of opioid alkaloids. PMID:25233364

  15. New mono- and diethynylsiloxysilsesquioxanes--efficient procedures for their synthesis.

    PubMed

    Dudziec, Beata; Rzonsowska, Monika; Marciniec, Bogdan; Brząkalski, Dariusz; Woźniak, Bartosz

    2014-09-21

    Ethynyl-substituted siloxysilsesquioxanes are promising building blocks for a wide range of substances based on a POSS/DDSQ core, especially for (oligo-)polymer syntheses and modifications (the formation of hybrid materials with interesting photophysical and mechanical properties). In this study, we report on a series of new mono- and diethynylsiloxysilsesquioxanes formed via an efficient and highly selective one-pot process from silsesquioxanes with reactive Si-OH groups based on sequential condensation, hydrolysis, chlorination and substitution reactions. All newly synthesized compounds were isolated and characterized by spectroscopic methods. PMID:25047114

  16. Stereoselective synthesis and molecular modeling of chiral cyclopentanes.

    PubMed

    Abdel-Jalil, Raid J; Steinbrecher, Thomas; Al-Harthy, Thuraya; Mahal, Ahmed; Abou-Zied, Osama K; Voelter, Wolfgang

    2015-10-13

    The reaction of 3-methyseleno-2-methylselenomethyl-propene with benzyl 2,3-anhydro-4-O-triflyl-β-L-ribopyranoside provides a major convenient enantiomeric product of 1-methylene-(benzyl3,4-dideoxy-α-D-arabinopyranoso)-[3,4-c]-cyclopentane, with benzyl-2,3-anhydro-4-deoxy-4-C-(2-methyl- propen-3-yl)-α-D-lyxopyranoside as a minor product. While the reaction of 3-methyseleno-2-[methylselenomethyl]-propene with benzyl 2,3-anhydro-4-O-triflyl-α-D-ribopyranoside produces a good yield of benzyl-2,3-anhydro-4-deoxy-4-C-(2-methylpropen-3-yl)-α-D-lyxo-pyranoside. Molecular modeling and molecular dynamics simulations indicate that the intermediate in the reaction of the β-L sugar frequently occupies an optimal conformation that leads to the formation of cyclopentane, while the intermediate in the reaction of the α-D sugar has a very small probability. The results point to the dominant role of the β-L sugar intermediate in controlling the cyclopentane formation. PMID:26267888

  17. Stereoselective Phytotoxicity of HCH Mediated by Photosynthetic and Antioxidant Defense Systems in Arabidopsis thaliana

    PubMed Central

    Zhang, Qiong; Zhou, Cong; Zhang, Quan; Qian, Haifeng; Liu, Weiping; Zhao, Meirong

    2013-01-01

    Background Hexachlorocyclohexane (HCH) has been used for plant protection and sanitation world-widely, and its isomers have been detected in water, soil, and air as well as in vegetation. As a sink for lipophilic pollutants, vegetation is very important for the degradation and fate of organic contamination; however, little was known about their phytotoxicity and mechanisms of toxic effect. In this study, the stereoselective phototoxicity of four isomers (α, β, γ, and δ) of HCHs mediated by independent as well as interconnecting systems of photosynthesis and enzymatic antioxidant defense system in Arabidopsis thaliana were assessed. Principal Findings Our results revealed that all the HCHs not only stimulated the activities of catalase (CAT) and peroxidase (POD), but also inhibited the activity of superoxide dismutase (SOD). In photosynthesis system, the photosynthetic efficiency of PSI and PSII were all down regulated. Meanwhile, results from both systems showed that δ-HCH was the most toxic one, while α-HCH the least in Arabidopsis thaliana. Conclusions For the first time, stereoselective effects of different isomers of HCH in plant were demonstrated. And the results suggest that it requires further research to fully elucidate the environmental toxicity and their mechanisms. PMID:23349669

  18. Synthesis of (-)-Cannabimovone and Structural Reassignment of Anhydrocannabimovone through Gold(I)-Catalyzed Cycloisomerization.

    PubMed

    Carreras, Javier; Kirillova, Mariia S; Echavarren, Antonio M

    2016-06-13

    The first total synthesis of cannabimovone from Cannabis sativa and anhydrocannabimovone was achieved by means of a highly stereoselective gold(I)-catalyzed cycloisomerization. The results led to reassignment of the structure of anhydrocannabimovone. PMID:27119910

  19. Total synthesis of (-)-spinosyn A.

    PubMed

    Mergott, Dustin J; Frank, Scott A; Roush, William R

    2004-08-17

    A convergent, highly stereoselective total synthesis of (-)-spinosyn A (1) is described. Key features of the synthesis include the transannular Diels-Alder reaction of macrocyclic pentaene 11 and the transannular Morita-Baylis-Hillman cyclization of 12 that generates tetracycle 26. The total synthesis of (-)-spinosyn A was completed by a sequence involving the highly beta-selective glycosidation reaction of 13 and glycosyl imidate 30. PMID:15173590

  20. Efficient synthesis of hexahydroindenopyridines and their potential as melatoninergic ligands.

    PubMed

    Párraga, Javier; Moreno, Laura; Diaz, Amelia; El Aouad, Noureddine; Galán, Abraham; Sanz, María Jesús; Caignard, Daniel-Henri; Figadère, Bruno; Cabedo, Nuria; Cortes, Diego

    2014-10-30

    Hexahydroindenopyridine (HHIP) is an interesting tricyclic piperidine nucleus that is structurally related to melatonin, a serotonin-derived neurohormone. Melatonin receptor ligands have applications in several cellular, neuroendocrine and neurophysiological disorders, including depression and/or insomnia. We report herein an efficient two-step method to prepare new HHIP via enamine C-alkylation-cyclization. The influence of substituents on the benzene ring and the nitrogen atom on melatoninergic receptors has been studied. Among the 25 synthesized HHIPs, some of them containing methylenedioxy (series 2) and 8-chloro-7-methoxy substituents (series 4) on the benzene ring revealed affinity for the MT1 and/or the MT2 receptors within the nanomolar range or low micromolar. Similar activities were also encountered for those presenting urea (4g), N-aryl (2e) and N-alkyl (2f) acetamide functions. Therefore, new synthesized compounds with a HHIP nucleus have emerged as new promising leads towards the discovery of melatoninergic ligands which could provide new therapeutic agents. PMID:25232966

  1. Information and Efficiency in the Nervous System—A Synthesis

    PubMed Central

    Sengupta, Biswa; Stemmler, Martin B.; Friston, Karl J.

    2013-01-01

    In systems biology, questions concerning the molecular and cellular makeup of an organism are of utmost importance, especially when trying to understand how unreliable components—like genetic circuits, biochemical cascades, and ion channels, among others—enable reliable and adaptive behaviour. The repertoire and speed of biological computations are limited by thermodynamic or metabolic constraints: an example can be found in neurons, where fluctuations in biophysical states limit the information they can encode—with almost 20–60% of the total energy allocated for the brain used for signalling purposes, either via action potentials or by synaptic transmission. Here, we consider the imperatives for neurons to optimise computational and metabolic efficiency, wherein benefits and costs trade-off against each other in the context of self-organised and adaptive behaviour. In particular, we try to link information theoretic (variational) and thermodynamic (Helmholtz) free-energy formulations of neuronal processing and show how they are related in a fundamental way through a complexity minimisation lemma. PMID:23935475

  2. Hangman corroles: efficient synthesis and oxygen reaction chemistry.

    PubMed

    Dogutan, Dilek K; Stoian, Sebastian A; McGuire, Robert; Schwalbe, Matthias; Teets, Thomas S; Nocera, Daniel G

    2011-01-12

    The construction of a new class of compounds--the hangman corroles--is provided efficiently by the modification of macrocyclic forming reactions from bilanes. Hangman cobalt corroles are furnished in good yields from a one-pot condensation of dipyrromethane with the aldehyde of a xanthene spacer followed by metal insertion using microwave irradiation. In high oxidation states, X-band EPR spectra and DFT calculations of cobalt corrole axially ligated by chloride are consistent with the description of a Co(III) center residing in the one-electron oxidized corrole macrocycle. These high oxidation states are likely accessed in the activation of O-O bonds. Along these lines, we show that the proton-donating group of the hangman platform works in concert with the redox properties of the corrole to enhance the catalytic activity of O-O bond activation. The hangman corroles show enhanced activity for the selective reduction of oxygen to water as compared to their unmodified counterparts. The oxygen adduct, prior to oxygen reduction, is characterized by EPR and absorption spectroscopy. PMID:21142043

  3. Efficient enzymatic synthesis of ampicillin by mutant Alcaligenes faecalis penicillin G acylase.

    PubMed

    Deng, Senwen; Su, Erzheng; Ma, Xiaoqiang; Yang, Shengli; Wei, Dongzhi

    2015-04-10

    Semi-synthetic β-lactam antibiotics (SSBAs) are one of the most important antibiotic families in the world market. Their enzymatic synthesis can be catalyzed by penicillin G acylases (PGAs). In this study, to improve enzymatic synthesis of ampicillin, site-saturating mutagenesis was performed on three conserved amino acid residues: βF24, αR146, and αF147 of thermo-stable penicillin G acylase from Alcaligenes faecalis (Af PGA). Four mutants βF24G, βF24A, βF24S, and βF24P were recovered by screening the mutant bank. Kinetic analysis of them showed up to 800-fold increased kcat/Km value for activated acyl donor D-phenylglycine methyl ester (D-PGME). When βF24G was used for ampicillin synthesis under kinetic control at industrially relevant conditions, 95% of nucleophile 6-aminopenicillanic acid (6-APA) was converted to ampicillin in aqueous medium at room temperature while 12% process time is needed to reach maximum product accumulation at 25% enzyme concentration compared with the wild-type Af PGA. Consequently, process productivity of enzymatic synthesis of ampicillin catalyzed by Af PGA was improved by more than 130 times, which indicated an enzyme viable for efficient SSBAs synthesis. PMID:25681630

  4. Highly Efficient Synthesis of Clean Biofuels from Biomass Using FeCuZnAlK Catalyst

    NASA Astrophysics Data System (ADS)

    Qiu, Song-bai; Xu, Yong; Ye, Tong-qi; Gong, Fei-yan; Yang, Zhi; Yamamoto, Mitsuo; Liu, Yong; Li, Quan-xin

    2011-12-01

    Highly efficient synthesis of clean biofuels using the bio-syngas obtained from biomass gasification was performed over Fe1.5Cu1Zn1Al1K0.117 catalyst. The maximum biofuel yield from the bio-syngas reaches about 1.59 kg biofuels/(kgcatal·h) with a contribution of 0.57 kg alcohols/(kgcatal·h) and 1.02 kg liquid hydrocarbons/(kgcatal·h). The alcohol products in the resulting biofuels were dominated by the C2+ alcohols (mainly C2—C6 alcohols) with a content of 73.55%-89.98%. The selectivity of the liquid hydrocarbons (C5+) in the hydrocarbon products ranges from 60.37% to 70.94%. The synthesis biofuels also possess a higher heat value of 40.53-41.49 MJ/kg. The effects of the synthesis conditions, including temperature, pressure, and gas hourly space velocity, on the biofuel synthesis were investigated in detail. The catalyst features were characterized by inductively coupled plasma and atomic emission spectroscopy, X-ray diffraction, temperature programmed reduction, and the N2 adsorption-desorption isotherms measurements. The present biofuel synthesis with a higher biofuel yield and a higher selectivity of liquid hydrocarbons and C2+ alcohols may be a potentially useful route to produce clean biofuels and chemicals from biomass.

  5. Total Synthesis of Laulimalide: Assembly of the Fragments and Completion of the Synthesis of the Natural Product and a Potent Analogue

    PubMed Central

    Trost, Barry M.; Amans, Dominique; Seganish, W. Michael; Chung, Cheol K.

    2012-01-01

    In this manuscript, we report the full account of our efforts to couple the northern and the southern building blocks, whose synthesis were described in the preceding paper, along with the modifications required which ultimately lead to a successful synthesis of laulimalide. Key highlights include an exceptionally efficient and atom-economical intramolecular ruthenium-catalyzed alkene-alkyne coupling to build the macrocycle followed by a highly stereoselective 1,3-allylic isomerization promoted by a rhenium complex. Interestingly, the designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity. We also report in this paper a second generation route which provided a more concise synthesis of the natural product. PMID:22307856

  6. Total Synthesis of Notoamides F, I, and R and Sclerotiamide.

    PubMed

    Zhang, Benxiang; Zheng, Weifeng; Wang, Xiaoqing; Sun, Deqian; Li, Chaozhong

    2016-08-22

    The total synthesis of the natural indole alkaloids (+)-notoamide F, I, and R and (-)-sclerotiamide is described. The four heptacyclic compounds were synthesized in 10-12 steps in a convergent and highly stereoselective manner from the readily available Seebach acetal. Key steps of the synthesis include a stereoselective oxidative aza-Prins cyclization to construct the bicyclo[2.2.2]diazaoctane, and a cobalt-catalyzed radical cycloisomerization to create the cyclohexenyl ring. PMID:27443750

  7. A Versatile Organocatalytic Approach for the Synthesis of Enantioenriched gem-Difluorinated Compounds.

    PubMed

    Saulnier, Steve; Ciardi, Moira; Lopez-Carrillo, Veronica; Gualandi, Andrea; Cozzi, Pier Giorgio

    2015-09-21

    The combination of a practical and highly enantioselective organocatalytic reaction, which allows the stereoselective introduction of a benzodithiol group, with a fluorination step, gives a new and effective strategy for the stereoselective synthesis of difluorinated building blocks. The benzodithiol group is a versatile and chameleonic group that can be further functionalized before fluorination, giving customized and tailored useful synthetic strategies. As an example of the application of this facile strategy, the effective enantioselective synthesis of difluoroarundic acid is described. PMID:26239866

  8. Au(I)-catalyzed efficient synthesis of functionalized bicyclo[3.2.0]heptanes.

    PubMed

    Li, Guotao; Huang, Xiaogen; Zhang, Liming

    2008-06-01

    An efficient Au(I)-catalyzed synthesis of highly strained and functionalized bicyclo[3.2.0]heptanes is developed. Subsequent couplings with various nucleophiles offer additional structural features/complexity. These one-pot, three-component reactions are proposed to proceed via a key 1,3-dipolar cycloaddition between a Au carbenoid-containing carbonyl ylide and ethyl vinyl ether. PMID:18465856

  9. Temporary Restraints to Overcome Steric Obstacles—Efficient Strategy for the Synthesis of Mycalamide B**

    PubMed Central

    Jewett, John C.; Rawal, Viresh H.

    2014-01-01

    Restrain and Release: An efficient synthesis of mycalamide B is reported. The synthetic route features (a) a one-pot Mukaiyama–Michael/epoxidation sequence to introduce three of the stereocenters found in the natural product, (b) an intramolecular isocyanate trapping to produce a rigid 10-membered cyclic carbamate, and (c) the selective opening of the cyclic carbamate to reveal the fully constructed natural product. PMID:20931583

  10. Rational design and synthesis of a porous, task-specific polycarbazole for efficient CO2 capture.

    PubMed

    Jin, Tian; Xiong, Yan; Zhu, Xiang; Tian, Ziqi; Tao, Duan-Jian; Hu, Jun; Jiang, De-en; Wang, Hualin; Liu, Honglai; Dai, Sheng

    2016-03-25

    We present a rational design and synthesis of a novel porous pyridine-functionalized polycarbazole for efficient CO2 capture based on the density functional theory calculations. The task-specific polymer, generated through a one-step FeCl3-catalyzed oxidative coupling reaction, exhibits a superior CO2 uptake at 1.0 bar and 273 K (5.57 mmol g(-1)). PMID:26864392

  11. Nano Clinoptilolite: Highly Efficient Catalyst for the Synthesis of Chromene Derivatives Under Solvent-Free Conditions.

    PubMed

    Hallajian, Sara; Khalilzadeh, Mohammad A; Tajbakhsh, Mahgol; Alipour, Eskandar; Safaei, Zahra

    2015-01-01

    An efficient and selective synthesis of substituted chromene derivatives via three-component reaction of 4-hydroxycoumarin or 1,3-dicarbonyl compounds, activated acetylenic compounds and N-nucleophiles is described. The reaction was conducted under solvent-free conditions at 70°C using potassium fluoride impregnated on natural zeolite as a cheap and available solid base. The procedure has several advantages involving selectivity, excellent yields and a convenient work-up method. PMID:25910084

  12. ACCESS 1: Approximation Concepts Code for Efficient Structural Synthesis program documentation and user's guide

    NASA Technical Reports Server (NTRS)

    Miura, H.; Schmit, L. A., Jr.

    1976-01-01

    The program documentation and user's guide for the ACCESS-1 computer program is presented. ACCESS-1 is a research oriented program which implements a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and general mathematical programming algorithms are applied in the design optimization procedure. Implementation of the computer program, preparation of input data and basic program structure are described, and three illustrative examples are given.

  13. Directed evolution of leucine dehydrogenase for improved efficiency of L-tert-leucine synthesis.

    PubMed

    Zhu, Lin; Wu, Zhe; Jin, Jian-Ming; Tang, Shuang-Yan

    2016-07-01

    L-tert-Leucine and its derivatives are used as synthetic building blocks for pharmaceutical active ingredients, chiral auxiliaries, and ligands. Leucine dehydrogenase (LeuDH) is frequently used to prepare L-tert-leucine from the α-keto acid precursor trimethylpyruvate (TMP). In this study, a high-throughput screening method for the L-tert-leucine synthesis reaction based on a spectrophotometric approach was developed. Directed evolution strategy was applied to engineer LeuDH from Lysinibacillus sphaericus for improved efficiency of L-tert-leucine synthesis. After two rounds of random mutagenesis, the specific activity of LeuDH on the substrate TMP was enhanced by more than two-fold, compared with that of the wild-type enzyme, while the activity towards its natural substrate, leucine, decreased. The catalytic efficiencies (k cat/K m) of the best mutant enzyme, H6, on substrates TMP and NADH were all enhanced by more than five-fold as compared with that of the wild-type enzyme. The efficiency of L-tert-leucine synthesis by mutant H6 was significantly improved. A productivity of 1170 g/l/day was achieved for the mutant enzyme H6, compared with 666 g/l/day for the wild-type enzyme. PMID:26898942

  14. A new structural analysis/synthesis capability - ACCESS. [Approximation Concepts Code for Efficient Structural Synthesis

    NASA Technical Reports Server (NTRS)

    Schmit, L. A.; Miura, H.

    1975-01-01

    The creation of an efficient automated capability for minimum weight design of structures is reported. The ACCESS 1 computer program combines finite element analysis techniques and mathematical programming algorithms using an innovative collection of approximation concepts. Design variable linking, constraint deletion techniques and approximate analysis methods are used to generate a sequence of small explicit mathematical programming problems which retain the essential features of the design problem. Organization of the finite element analysis is carefully matched to the design optimization task. The efficiency of the ACCESS 1 program is demonstrated by giving results for several example problems.

  15. An efficiently sustainable dextran-based flocculant: Synthesis, characterization and flocculation.

    PubMed

    Li, Ruo-Han; Zhang, Hong-Bin; Hu, Xue-Qin; Gan, Wei-Wei; Li, Qiu-Ping

    2016-09-01

    Polysaccharide-modified flocculant is a notable material in the field of wastewater treatment. Synthesis of biopolysaccharide derivatives as eco-friendly flocculants is remarkably desired for environmental protection. This work presents an efficient flocculant synthesized through copolymerization of acrylamide, sodium acrylate (AS), and dextran. Physicochemical properties of the flocculant were evaluated. Process parameters of coal-washing wastewater flocculation were tested using Response Surface Method. The application of graft polymers exhibited efficient flocculation performance at low level of flocculant dosage in alkalescent environment. The improved dextran contributes to handle industrial effluent and sanitary sewage. PMID:27317940

  16. Efficient synthesis of [18F]trifluoromethane and its application in the synthesis of PET tracers.

    PubMed

    van der Born, Dion; Herscheid, J Koos D M; Orru, Romano V A; Vugts, Danielle J

    2013-05-11

    A new strategy towards [(18)F]trifluoromethyl-containing compounds is developed. [(18)F]trifluoromethane is synthesised in a fast and efficient manner and subsequently used in the reaction with aldehydes and ketones forming [(18)F]trifluoromethyl carbinols in good yields. PMID:23563284

  17. Simplified Application of Material Efficiency Green Metrics to Synthesis Plans: Pedagogical Case Studies Selected from "Organic Syntheses"

    ERIC Educational Resources Information Center

    Andraos, John

    2015-01-01

    This paper presents a simplified approach for the application of material efficiency metrics to linear and convergent synthesis plans encountered in organic synthesis courses. Computations are facilitated and automated using intuitively designed Microsoft Excel spreadsheets without invoking abstract mathematical formulas. The merits of this…

  18. Efficient Synthesis of 3,3'-Mixed Bisindoles via Lewis Acid Catalyzed Reaction of Spiro-epoxyoxindoles and Indoles.

    PubMed

    Hajra, Saumen; Maity, Subrata; Maity, Ramkrishna

    2015-07-17

    An efficient strategy for the synthesis of 3-(3-indolyl)-oxindole-3-methanol has been developed to achieve a Lewis acid catalyzed, highly regioselective ring opening of spiro-epoxyoxindoles with indoles. The method is used for the gram-scale formal total synthesis of (±)-gliocladin C. PMID:26158390

  19. Molecular basis for the substrate stereoselectivity in Tryptophan Dioxygenase

    PubMed Central

    Capece, Luciana; Lewis-Ballester, Ariel; Marti, Marcelo A.; Estrin, Dario A.; Yeh, Syun-Ru

    2011-01-01

    Tryptophan dioxygenase (TDO) and Indoleamine 2,3 dioxygenase (IDO) are the only two heme-proteins that catalyze the oxidation reaction of tryptophan (Trp) to N-formylkynurenine (NFK). While human IDO (hIDO) is able to oxidize both L and D-Trp, human TDO (hTDO) displays a major specificity towards L-Trp. In this work we aim to interrogate the molecular basis for the substrate stereoselectivity of hTDO. Our previous molecular dynamics simulation studies of Xanthomonas campestris TDO (xcTDO) showed that an H-bond between T254 (T342 in hTDO) and the ammonium group of the substrate is present in the L-Trp-bound enzyme, but not in the D-Trp bound enzyme. The fact that this is the only notable structural alteration induced by the change in the stereo structure of the substrate prompted us to produce and characterize the T342A mutant of hTDO to evaluate the structural role of T342 in controlling the substrate stereoselectivity of the enzyme. The experimental results indicate that the mutation only slightly perturbs the global structural properties of the enzyme, but it totally abolishes the substrate stereoselectivity. Molecular Dynamics simulations of xcTDO show that T254 controls the substrate stereoselectivity of the enzyme by (i) modulating the H-bonding interaction between the NH3+ group and epoxide oxygen of the ferryl/indole 2,3-epoxide intermediate of the enzyme, and (ii) regulating the dynamics of two active site loops, loop250–260 and loop117–130, critical for substrate-binding. PMID:22082147

  20. Twofold polyketide branching by a stereoselective enzymatic Michael addition.

    PubMed

    Heine, Daniel; Sundaram, Srividhya; Bretschneider, Tom; Hertweck, Christian

    2015-06-18

    The versatility of the branching module of the rhizoxin polyketide synthase was tested in an in vitro enzyme assay with a polyketide mimic and branched (di)methylmalonyl-CoA extender units. Comparison of the products with synthetic reference compounds revealed that the module is able to stereoselectively introduce two branches in one step by a Michael addition-lactonisation sequence, thus expanding the scope of previously studied PKS systems. PMID:25994388

  1. Copper-catalyzed stereoselective conjugate addition of alkylboranes to alkynoates

    PubMed Central

    Wakamatsu, Takamichi; Nagao, Kazunori

    2015-01-01

    Summary A copper-catalyzed conjugate addition of alkylboron compounds (alkyl-9-BBN, prepared by hydroboration of alkenes with 9-BBN-H) to alkynoates to form β-disubstituted acrylates is reported. The addition occurred in a formal syn-hydroalkylation mode. The syn stereoselectivity was excellent regardless of the substrate structure. A variety of functional groups were compatible with the conjugate addition. PMID:26734092

  2. Stereoselective Formation of Fully Substituted Ketone Enolates.

    PubMed

    Haimov, Elvira; Nairoukh, Zackaria; Shterenberg, Alexander; Berkovitz, Tiran; Jamison, Timothy F; Marek, Ilan

    2016-04-25

    The application of stereochemically defined acyclic fully substituted enolates of ketones to the enantioselective synthesis of quaternary carbon stereocenters would be highly valuable. Herein, we describe an approach leading to the formation of several new stereogenic centers through a combined metalation-addition of a carbonyl-carbamoyl transfer to reveal in situ stereodefined α,α-disubstituted enolates of ketone as a single stereoisomer. This approach could produce a series of aldol and Mannich products from enol carbamate with excellent diastereomeric ratios. PMID:27027778

  3. Stereoselective Luche reduction of deoxynivalenol and three of its acetylated derivatives at C8.

    PubMed

    Fruhmann, Philipp; Hametner, Christian; Mikula, Hannes; Adam, Gerhard; Krska, Rudolf; Fröhlich, Johannes

    2014-01-01

    The trichothecene mycotoxin deoxynivalenol (DON) is a well known and common contaminant in food and feed. Acetylated derivatives and other biosynthetic precursors can occur together with the main toxin. A key biosynthetic step towards DON involves an oxidation of the 8-OH group of 7,8-dihydroxycalonectrin. Since analytical standards for the intermediates are not available and these intermediates are therefore rarely studied, we aimed for a synthetic method to invert this reaction, making a series of calonectrin-derived precursors accessible. We did this by developing an efficient protocol for stereoselective Luche reduction at C8. This method was used to access 3,7,8,15-tetrahydroxyscirpene, 3-deacetyl-7,8-dihydroxycalonectrin, 15-deacetyl-7,8-dihydroxycalonectrin and 7,8-dihydroxycalonectrin, which were characterized using several NMR techniques. Beside the development of a method which could basically be used for all type B trichothecenes, we opened a synthetic route towards different acetylated calonectrins. PMID:24434906

  4. Facile and efficient one-pot synthesis of benzimidazoles using lanthanum chloride

    PubMed Central

    2013-01-01

    Background We report the synthesis of benzimidazoles using lanthanum chloride as an efficient catalyst. One-pot synthesis of 2-substituted benzimidazole derivatives from o-phenylenediamine and a variety of aldehydes were developed under mild reaction conditions. Results We have examined the effect of different solvents using the same reaction conditions. The yield of the product varied with the nature of the solvents, and better conversion and easy isolation of products were found with acetonitrile. In a similar manner, the reaction with o-phenylenediamine and 3,4,5-trimethoxybenzaldehyde was carried out without any solvents. The observation shows that the reaction was not brought into completion, even after starting for a period of 9 h, and the reaction mixture showed a number of spots in thin-layer chromatography. Conclusions In conclusion, lanthanum chloride has been employed as a novel and efficient catalyst for the synthesis of benzimidazoles in good yields from o-phenylenediamine and a wide variety of aldehydes. All of the reactions were carried out in the presence of lanthanum chloride (10 mol%) in acetonitrile at room temperature. PMID:23919542

  5. N-triazinylammonium tetrafluoroborates. A new generation of efficient coupling reagents useful for peptide synthesis.

    PubMed

    Kamiński, Zbigniew J; Kolesińska, Beata; Kolesińska, Justyna; Sabatino, Giuseppina; Chelli, Mario; Rovero, Paolo; Błaszczyk, Michał; Główka, Marek L; Papini, Anna Maria

    2005-12-01

    A new generation of triazine-based coupling reagents (TBCRs), designed according to the concept of "superactive esters", was obtained by treatment of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) chloride with lithium or silver tetrafluoroborate. The structure of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate was confirmed by X-ray diffraction. Activation of carboxylic acids by using this reagent proceeds via triazine "superactive ester". The coupling reagent was successfully used for the synthesis of Z-, Boc-, and Fmoc-protected dipeptides derived from natural and unnatural sterically hindered amino acids and for fragment condensation, in 80-100% yield and with high enantiomeric purity. The manual SPPS of the ACP(65-74) peptide fragment (H-Val-Gln-Ala-Ala-Ile-Asp-Tyr-Ile-Asn-Gly-OH) proceeded significantly faster than with TBTU or HATU, as well as the automated SPPS of the same fragment gave a purer product than by using TBTU or PyBOP. The reagent was also demonstrated to be efficient in on-resin head-to-tail cyclization of constrained cyclopeptides, in SPPS synthesis of Aib peptides, and in the synthesis of esters from appropriate acids, alcohols, and phenols. The high efficiency and versatility of this new generation of TBCRs confirm, for the first time, the usefulness of the concept of "superactive esters" in rational design of the structure of coupling reagents. PMID:16316237

  6. The Stereoselective Reductions of Ketones to the Most Thermodynamically Stable Alcohols Using Lithium and Hydrated Salts of Common Transition Metals.

    PubMed

    Kennedy, Nicole; Cohen, Theodore

    2015-08-21

    A simple method is presented for the highly stereoselective reductions of ketones to the most thermodynamically stable alcohols. In this procedure, the ketone is treated with lithium dispersion and either FeCl2·4H2O or CuCl2·2H2O in THF at room temperature. This protocol is applied to a large number and variety of ketones and is both more convenient and efficient than those commonly reported for the diastereoselective reduction of five- and six-membered cyclic ketones. PMID:26226182

  7. Enediyne Polyketide Synthases Stereoselectively Reduce the β-Ketoacyl Intermediates to β-d-Hydroxyacyl Intermediates in Enediyne Core Biosynthesis

    PubMed Central

    2015-01-01

    PKSE biosynthesizes an enediyne core precursor from decarboxylative condensation of eight malonyl-CoAs. The KR domain of PKSE is responsible for iterative β-ketoreduction in each round of polyketide chain elongation. KRs from selected PKSEs were investigated in vitro with β-ketoacyl-SNACs as substrate mimics. Each of the KRs reduced the β-ketoacyl-SNACs stereoselectively, all affording the corresponding β-d-hydroxyacyl-SNACs, and the catalytic efficiencies (kcat/KM) of the KRs increased significantly as the chain length of the β-ketoacyl-SNAC substrate increases. PMID:25019332

  8. Rhodium-Catalyzed Regio- and Stereoselective [2 + 2] Cycloaddition of Allenamides.

    PubMed

    Zheng, Wei-Feng; Bora, Pranjal Protim; Sun, Gui-Jun; Kang, Qiang

    2016-08-01

    A highly regio- and stereoselective Rh-catalyzed intermolecular head-to-head [2 + 2] cycloaddition of allenamides was developed. The intermolecular cycloadducts, trans-dimethylenecyclobutane-1,2-diamine derivatives, were achieved in good yields with high regioselectivity and stereoselectivity. PMID:27403894

  9. Iron-Catalyzed Stereoselective Cross-Coupling Reactions of Stereodefined Enol Carbamates with Grignard Reagents.

    PubMed

    Rivera, Ana Cristina Parra; Still, Raymond; Frantz, Doug E

    2016-06-01

    A practical and highly stereoselective iron-catalyzed cross-coupling reaction of stereodefined enol carbamates and Grignard reagents to yield tri- and tetrasubstituted acrylates is reported. A facile method for the stereoselective generation of these enol carbamates has also been developed. PMID:27088754

  10. A Sustainable and Efficient Synthesis of Benzyl Phosphonates Using PEG/KI Catalytic System

    PubMed Central

    Disale, Shamrao; Kale, Sandip; Abraham, George; Kahandal, Sandeep; Sawarkar, Ashish N.; Gawande, Manoj B.

    2016-01-01

    An efficient and expedient protocol for the synthesis of benzyl phosphonates using KI/K2CO3 as a catalytic system and PEG-400 as benign solvent has been developed. The reaction proceeds smoothly at room temperature achieving excellent selectivity and yield of the corresponding products. The combination of PEG-400, KI, and K2CO3 in this reaction avoids the need of volatile/toxic organic solvents and reactive alkali metals or metal nanoparticles/hydrides. We believe that this benign combination (PEG-400 and KI) could be used for other related organic transformations. PMID:27579301

  11. Template-free synthesis of Ta3N5 nanorod arrays for efficient photoelectrochemical water splitting.

    PubMed

    Zhen, Chao; Wang, Lianzhou; Liu, Gang; Lu, Gao Qing Max; Cheng, Hui-Ming

    2013-04-14

    We report the template-free synthesis of Ta3N5 nanorod array films grown on Ta foil by a combination of a vapor-phase hydrothermal process and subsequent nitriding. The Ta3N5 nanorod array film modified with Co(OH)x when used as a photoanode in a photoelectrochemical cell for water splitting yields a stable photocurrent density of 2.8 mA cm(-2) at 1.23 VRHE under AM 1.5G simulated sunlight. The incident photon-to-current conversion efficiency at 480 nm is determined to be 37.8%. PMID:23463440

  12. A Sustainable and Efficient Synthesis of Benzyl Phosphonates Using PEG/KI Catalytic System.

    PubMed

    Disale, Shamrao; Kale, Sandip; Abraham, George; Kahandal, Sandeep; Sawarkar, Ashish N; Gawande, Manoj B

    2016-01-01

    An efficient and expedient protocol for the synthesis of benzyl phosphonates using KI/K2CO3 as a catalytic system and PEG-400 as benign solvent has been developed. The reaction proceeds smoothly at room temperature achieving excellent selectivity and yield of the corresponding products. The combination of PEG-400, KI, and K2CO3 in this reaction avoids the need of volatile/toxic organic solvents and reactive alkali metals or metal nanoparticles/hydrides. We believe that this benign combination (PEG-400 and KI) could be used for other related organic transformations. PMID:27579301

  13. An Efficient Protection-Free One-Pot Chemical Synthesis of Modified Nucleoside-5'-Triphosphates.

    PubMed

    Shanmugasundaram, Muthian; Senthilvelan, Annamalai; Xiao, Zejun; Kore, Anilkumar R

    2016-07-01

    A simple, reliable, and an efficient "one-pot, three step" chemical method for the synthesis of modified nucleoside triphosphates such as 5-methylcytidine-5'-triphosphate (5-MeCTP), pseudouridine-5'-triphosphate (pseudoUTP) and N(1)-methylpseudouridine-5'-triphosphate (N(1)-methylpseudoUTP) starting from the corresponding nucleoside is described. The overall reaction involves the monophosphorylation of nucleoside, followed by the reaction with pyrophosphate and subsequent hydrolysis of the cyclic intermediate to furnish the corresponding NTP in moderate yields with high purity (>99.5%). PMID:27159048

  14. An efficient chemical synthesis of carboxylate-isostere analogs of daptomycin

    PubMed Central

    Yoganathan, Sabesan; Yin, Ning; He, Yong; Mesleh, Michael; Gu, Yu Gui; Miller, Scott J.

    2014-01-01

    Herein we report a direct and efficient method for the synthesis of four new carboxylate-isostere analogs of daptomycin. The side chain carboxylic acid moieties of the aspartic acids (Asp-3, Asp-7 and Asp-9) and β-methyl glutamic acid (MeGlu-12) were all converted into the corresponding carboxylate isosteres using direct synthetic procedures. The present study also describes an esterification protocol to overcome the possible backbone cyclization of the activated side chain carboxylic acid group of either Asp or Glu, onto the backbone amide. PMID:23752953

  15. Synthesis of Ordered Mesoporous Silica for Energy-efficient Adsorption Systems

    NASA Astrophysics Data System (ADS)

    Endo, Akira; Komori, Kou; Inagi, Yuki; Fujisaki, Satoko; Yamamoto, Takuji

    Energy-efficient adsorption systems, such as adsorption heat pump, desiccant cooling, humidity control system, and so on, are expected as a energy exchange process because they are able to utilize low temperature exhaust heat. As an adsorbent for such systems, materials with large adsorption capacity in the pressure range of practical operation are preferable. To enable the design and synthesis of materials with large heat storage capacity, the pore structure of adsorbents should be optimized for each systems. In this paper, we synthesized ordered mesoporous silica (MPS) with an arrow pore size distribution of around 2nm by a solvent evaporation method and evaluated their water adsorption properties. The adsorption isotherms for MPSs showed steep increase at a relative humidity corresponding to their pore size. Since MPSs have a large adsorption capacity than conventional materials in the relative humidity region of practical operation, they are expected for new adsorbents for energy-efficient adsorption systems.

  16. Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations.

    PubMed

    Nicolaou, K C; Wang, Yanping; Lu, Min; Mandal, Debashis; Pattanayak, Manas R; Yu, Ruocheng; Shah, Akshay A; Chen, Jason S; Zhang, Hongjun; Crawford, James J; Pasunoori, Laxman; Poudel, Yam B; Chowdari, Naidu S; Pan, Chin; Nazeer, Ayesha; Gangwar, Sanjeev; Vite, Gregory; Pitsinos, Emmanuel N

    2016-07-01

    From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy. PMID:27266267

  17. Regio- and stereoselective Pd-catalyzed direct arylation of unactivated sp(3) C(3)-H bonds of tetrahydrofuran and 1,4-benzodioxane systems.

    PubMed

    Parella, Ramarao; Babu, Srinivasarao Arulananda

    2015-02-20

    An auxiliary-enabled Pd-catalyzed highly regio- and stereoselective sp(3) C-H activation and the direct arylation of the C3-position of oxygen heterocycles, such as tetrahydrofuran and 1,4-benzodioxane systems, are reported. An efficient stereoselective construction of cis 2,3-disubstituted tetrahydrofuran derivatives (analogues of norlignans) and cis 2,3-disubstituted 1,4-benzodioxane derivatives (analogues of neolignans) is described. The direct C(sp(3))-H arylation of the C3-position of (R)- or (S)- tetrahydrofuran-2-carboxamides furnished the corresponding (2R,3R) and (2S,3S) C3-arylated THF scaffolds as major compounds with very high regio- and diastereoselectivities. The stereochemistry of the products obtained in this work were unambiguously assigned on the basis of the X-ray structure analyses of representative compounds 3b, 3e, 4p, and 7. PMID:25588549

  18. Fungi as an efficient mycosystem for the synthesis of metal nanoparticles: progress and key aspects of research.

    PubMed

    Yadav, Alka; Kon, Kateryna; Kratosova, Gabriela; Duran, Nelson; Ingle, Avinash P; Rai, Mahendra

    2015-11-01

    Nanotechnology is an emerging cutting-edge technology, which involves interdisciplinary subjects, such as physics, chemistry, biology, material science and medicine. Different methods for the synthesis of nanoparticles have been discussed here. Although physical and chemical methods have been successfully used to synthesize nanoparticles, the use of hazardous chemicals and synthesis at high temperature is a matter of concern. Hence, there is a necessity to develop eco-friendly techniques for the synthesis of nanoparticles. Biosynthesis of nanoparticles by fungi, bacteria, actinomycetes, lichen and viruses have been reported eco-friendly. Moreover, the fungal system has emerged as an efficient system for nanoparticle synthesis as fungi possess distinctive characters including high wall binding capacity, easy to culture and simpler biomass handling, etc. In this review, we have discussed fungi as an important tool for the fabrication of nanoparticles. In addition, methods and mechanism for synthesis of nanoparticles and its potential applications have also been discussed. PMID:26164702

  19. A coenzyme-independent decarboxylase/oxygenase cascade for the efficient synthesis of vanillin.

    PubMed

    Furuya, Toshiki; Miura, Misa; Kino, Kuniki

    2014-10-13

    Vanillin is one of the most widely used flavor compounds in the world as well as a promising versatile building block. The biotechnological production of vanillin from plant-derived ferulic acid has attracted much attention as a new alternative to chemical synthesis. One limitation of the known metabolic pathway to vanillin is its requirement for expensive coenzymes. Here, we developed a novel route to vanillin from ferulic acid that does not require any coenzymes. This artificial pathway consists of a coenzyme-independent decarboxylase and a coenzyme-independent oxygenase. When Escherichia coli cells harboring the decarboxylase/oxygenase cascade were incubated with ferulic acid, the cells efficiently synthesized vanillin (8.0 mM, 1.2 g L(-1) ) via 4-vinylguaiacol in one pot, without the generation of any detectable aromatic by-products. The efficient method described here might be applicable to the synthesis of other high-value chemicals from plant-derived aromatics. PMID:25164030

  20. Controlling stereoselectivity by enzymatic and chemical means to access enantiomerically pure (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline derivatives☆

    PubMed Central

    Orden, Alejandro A.; Schrittwieser, Joerg H.; Resch, Verena; Mutti, Francesco G.; Kroutil, Wolfgang

    2013-01-01

    A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial ω-transaminases, and the diastereoselective reduction of a Bischler–Napieralski imine intermediate by catalytic hydrogenation in the presence of palladium on charcoal, leading exclusively to the desired cis-isomer. PMID:24503964

  1. Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms.

    PubMed

    Bagnall, John; Malia, Louis; Lubben, Anneke; Kasprzyk-Hordern, Barbara

    2013-10-01

    Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds. PMID:23886544

  2. Stereoselective Hydrolysis of Organophosphate Nerve Agents by the Bacterial Phosphotriesterase†

    PubMed Central

    Tsai, Ping-Chuan; Bigley, Andrew; Li, Yingchun; Ghanem, Eman; Cadieux, C. Linn; Kasten, Shane A.; Reeves, Tony E.; Cerasoli, Douglas M.; Raushel, Frank M.

    2010-01-01

    Organophosphorus compounds include many synthetic, neurotoxic substances that are commonly used as insecticides. The toxicity of these compounds is due to their ability to inhibit the enzyme acetylcholine esterase. Some of the most toxic organophosphates have been adapted for use as chemical warfare agents; the most well known are GA, GB, GD, GF, VX and VR. All of these compounds contain a chiral phosphorus center with the SP-enantiomers being significantly more toxic than the RP-enantiomers. Phosphotriesterase (PTE) is an enzyme capable of detoxifying these agents, but the stereochemical preference of the wild-type enzyme is for the RP-enantiomers. A series of enantiomerically pure chiral nerve agent analogues has been developed containing the relevant phosphoryl centers found in GB, GD, GF, VX and VR. Wild-type and mutant forms of PTE have been tested for their ability to hydrolyze this series of compounds. Mutant forms of PTE with significantly enhanced, as well as relaxed or reversed stereoselectivity, have been identified. A number of variants showed dramatically improved kinetic constants for the catalytic hydrolysis of the more toxic SP-enantiomers. Improvements of up to three orders of magnitude relative to the wild type enzyme were observed. Some of these mutants were tested against racemic mixtures of GB and GD. The kinetic constants obtained with the chiral nerve agent analogues accurately predict the improved activity and stereoselectivity against the authentic nerve agents used in this study. PMID:20701311

  3. Opposite Stereoselectivities of Dirigent Proteins in Arabidopsis and Schizandra Species*

    PubMed Central

    Kim, Kye-Won; Moinuddin, Syed G. A.; Atwell, Kathleen M.; Costa, Michael A.; Davin, Laurence B.; Lewis, Norman G.

    2012-01-01

    How stereoselective monolignol-derived phenoxy radical-radical coupling reactions are differentially biochemically orchestrated in planta, whereby for example they afford (+)- and (−)-pinoresinols, respectively, is both a fascinating mechanistic and evolutionary question. In earlier work, biochemical control of (+)-pinoresinol formation had been established to be engendered by a (+)-pinoresinol-forming dirigent protein in Forsythia intermedia, whereas the presence of a (−)-pinoresinol-forming dirigent protein was indirectly deduced based on the enantiospecificity of downstream pinoresinol reductases (AtPrRs) in Arabidopsis thaliana root tissue. In this study of 16 putative dirigent protein homologs in Arabidopsis, AtDIR6, AtDIR10, and AtDIR13 were established to be root-specific using a β-glucuronidase reporter gene strategy. Of these three, in vitro analyses established that only recombinant AtDIR6 was a (−)-pinoresinol-forming dirigent protein, whose physiological role was further confirmed using overexpression and RNAi strategies in vivo. Interestingly, its closest homolog, AtDIR5, was also established to be a (−)-pinoresinol-forming dirigent protein based on in vitro biochemical analyses. Both of these were compared in terms of properties with a (+)-pinoresinol-forming dirigent protein from Schizandra chinensis. In this context, sequence analyses, site-directed mutagenesis, and region swapping resulted in identification of putative substrate binding sites/regions and candidate residues controlling distinct stereoselectivities of coupling modes. PMID:22854967

  4. Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides of DL-alanine and N-(tert-butoxycarbonyl)-DL-alanine

    NASA Technical Reports Server (NTRS)

    Profy, A. T.; Usher, D. A.

    1984-01-01

    The aminoacylation of diinosine monophosphate was studied experimentally. When the acylating agent was the imidazolide of N-(tert-butoxycarbonyl)-DL-alanine, a 40 percent enantiomeric excess of the isomer was incorporated at the 2' site and the positions of equilibrium for the reversible 2'-3' migration reaction differed for the D and L enantiomers. The reactivity of the nucleoside hydroxyl groups was found to decrease on the order 2'(3') less than internal 2' and less than 5', and the extent of the reaction was affected by the concentration of the imidazole buffer. Reaction of IpI with imidazolide of unprotected DL-alanine, by contrast, led to an excess of the D isomer at the internal 2' site. Finally, reaction with the N-carboxy anhydride of DL-alanine occurred without stereoselection. These results are found to be relevant to the study of the evolution of optical chemical activity and the origin of genetically directed protein synthesis.

  5. Origins of stereoselectivity in evolved ketoreductases

    PubMed Central

    Noey, Elizabeth L.; Tibrewal, Nidhi; Jiménez-Osés, Gonzalo; Osuna, Sílvia; Park, Jiyong; Bond, Carly M.; Cascio, Duilio; Liang, Jack; Zhang, Xiyun; Huisman, Gjalt W.; Tang, Yi; Houk, Kendall N.

    2015-01-01

    Mutants of Lactobacillus kefir short-chain alcohol dehydrogenase, used here as ketoreductases (KREDs), enantioselectively reduce the pharmaceutically relevant substrates 3-thiacyclopentanone and 3-oxacyclopentanone. These substrates differ by only the heteroatom (S or O) in the ring, but the KRED mutants reduce them with different enantioselectivities. Kinetic studies show that these enzymes are more efficient with 3-thiacyclopentanone than with 3-oxacyclopentanone. X-ray crystal structures of apo- and NADP+-bound selected mutants show that the substrate-binding loop conformational preferences are modified by these mutations. Quantum mechanical calculations and molecular dynamics (MD) simulations are used to investigate the mechanism of reduction by the enzyme. We have developed an MD-based method for studying the diastereomeric transition state complexes and rationalize different enantiomeric ratios. This method, which probes the stability of the catalytic arrangement within the theozyme, shows a correlation between the relative fractions of catalytically competent poses for the enantiomeric reductions and the experimental enantiomeric ratio. Some mutations, such as A94F and Y190F, induce conformational changes in the active site that enlarge the small binding pocket, facilitating accommodation of the larger S atom in this region and enhancing S-selectivity with 3-thiacyclopentanone. In contrast, in the E145S mutant and the final variant evolved for large-scale production of the intermediate for the antibiotic sulopenem, R-selectivity is promoted by shrinking the small binding pocket, thereby destabilizing the pro-S orientation. PMID:26644568

  6. Origins of stereoselectivity in evolved ketoreductases.

    PubMed

    Noey, Elizabeth L; Tibrewal, Nidhi; Jiménez-Osés, Gonzalo; Osuna, Sílvia; Park, Jiyong; Bond, Carly M; Cascio, Duilio; Liang, Jack; Zhang, Xiyun; Huisman, Gjalt W; Tang, Yi; Houk, Kendall N

    2015-12-22

    Mutants of Lactobacillus kefir short-chain alcohol dehydrogenase, used here as ketoreductases (KREDs), enantioselectively reduce the pharmaceutically relevant substrates 3-thiacyclopentanone and 3-oxacyclopentanone. These substrates differ by only the heteroatom (S or O) in the ring, but the KRED mutants reduce them with different enantioselectivities. Kinetic studies show that these enzymes are more efficient with 3-thiacyclopentanone than with 3-oxacyclopentanone. X-ray crystal structures of apo- and NADP(+)-bound selected mutants show that the substrate-binding loop conformational preferences are modified by these mutations. Quantum mechanical calculations and molecular dynamics (MD) simulations are used to investigate the mechanism of reduction by the enzyme. We have developed an MD-based method for studying the diastereomeric transition state complexes and rationalize different enantiomeric ratios. This method, which probes the stability of the catalytic arrangement within the theozyme, shows a correlation between the relative fractions of catalytically competent poses for the enantiomeric reductions and the experimental enantiomeric ratio. Some mutations, such as A94F and Y190F, induce conformational changes in the active site that enlarge the small binding pocket, facilitating accommodation of the larger S atom in this region and enhancing S-selectivity with 3-thiacyclopentanone. In contrast, in the E145S mutant and the final variant evolved for large-scale production of the intermediate for the antibiotic sulopenem, R-selectivity is promoted by shrinking the small binding pocket, thereby destabilizing the pro-S orientation. PMID:26644568

  7. Synthesis and Evaluation of Tetramethylguanidinium-Polyethylenimine Polymers as Efficient Gene Delivery Vectors

    PubMed Central

    Mahato, Manohar; Yadav, Santosh; Kumar, Pradeep; Sharma, Ashwani Kumar

    2014-01-01

    Previously, we demonstrated that 6-(N,N,N′,N′-tetramethylguanidinium chloride)-hexanoyl-polyethylenimine (THP) polymers exhibited significantly enhanced transfection efficiency and cell viability. Here, in the present study, we have synthesized a series of N,N,N′,N′-tetramethylguanidinium-polyethylenimine (TP1-TP5) polymers via a single-step reaction involving peripheral primary amines of bPEI and varying amounts of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). These polymers were found to interact efficiently with negatively charged pDNA and formed stable complexes in the size range of ~240–450 nm. Acid-base titration profiles revealed improved buffering capacity of TP polymers as compared to bPEI. Transfection and cytotoxicity assays performed with TP/pDNA complexes on HEK293, CHO, and HeLa cells showed significantly higher transfection efficiency and cell viability with one of the complexes, TP2/pDNA complex, exhibited the highest transfection efficiency (~1.4–2.3-fold) outcompeting native bPEI and the commercially available transfection reagent, Lipofectamine 2000. Compared to previously reported THP polymers, the transfection efficiency of TP/pDNA complexes was found to be lower, as examined by flow cytometry. These results highlight the importance of the hydrophobic C-6 linker in THP polymers in forming compact nanostructures with pDNA, which might lead to efficient uptake and internalization of the complexes; however, the projected TP polymers offer an advantage of their rapid and economical one-step synthesis. PMID:24864245

  8. Catalytic asymmetric synthesis of enantioenriched heterocycles bearing a C-CF3 stereogenic center.

    PubMed

    Huang, Yi-Yong; Yang, Xing; Chen, Zhuo; Verpoort, Francis; Shibata, Norio

    2015-06-01

    Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles. PMID:25736019

  9. Stereoselective chemical defense in the Drosophila parasitoid Leptopilina heterotoma is mediated by (-)-iridomyrmecin and (+)-isoiridomyrmecin.

    PubMed

    Stökl, Johannes; Hofferberth, John; Pritschet, Maria; Brummer, Michael; Ruther, Joachim

    2012-04-01

    Chemical defense mechanisms are widespread among insects but have rarely been demonstrated in parasitoid wasps. Here, we show that the Drosophila parasitoid Leptopilina heterotoma (Hymenoptera, Figitidae) produces (-)-iridomyrmecin and (+)-isoiridomyrmecin in a cephalic gland, and that these chemicals have a highly repellent effect on ants. Stereoselective synthesis of 4 stereoisomers of iridomyrmecin allowed us to demonstrate that the repellent effect of iridomyrmecins depends on the stereochemistry. Potential food items impregnated with natural doses of (-)-iridomyrmecin were avoided by ants much longer than those impregnated with (+)-iridomyrmecin, (+)-isoiridomyrmecin, or (-)-isoiridomyrmecin, respectively. Quantitative headspace analyses revealed furthermore that females and males of L. heterotoma released iridomyrmecins in higher amounts when confronted with ants. This is the first time, that (-)-iridomyrmecin and (+)-isoiridomyrmecin are reported as natural products. Females synthesize more iridomyrmecins than males, and the most active (-)-iridomyrmecin is produced by females only. We, therefore, hypothesize that this defense mechanism is used mainly by female wasps when foraging for Drosophila larvae on rotten fruits, but also may protect male wasps during dispersal. PMID:22477024

  10. A library of spirooxindoles based on a stereoselective three-component coupling reaction.

    PubMed

    Lo, Michael M-C; Neumann, Christopher S; Nagayama, Satoshi; Perlstein, Ethan O; Schreiber, Stuart L

    2004-12-15

    A collection of structurally complex and chemically diverse small molecules is a useful tool to explore cell circuitry. In this article, we report the split-pool synthesis of more than 3000 spirooxindoles on high capacity macrobeads. The key reaction to assemble the spirooxindole core stereoselectively is a Lewis acid variant of the Williams' three-component coupling. After formation, the skeleton was elaborated using Sonogashira couplings, amide forming reactions, and N-acylations of gamma-lactams. The final library was analyzed by sampling individual macrobeads and by using binomial confidence limits. It was determined that at least 82% of the library compounds should have better than 80% purity. To demonstrate the utility of our discovery process, a high-throughput chemical genetic modifier screen was performed using stock solutions of the resultant products. A number of positives were identified as enhancers of the cellular actions of latrunculin B, an actin polymerization inhibitor. Through resynthesis, we confirmed one of the positives and demonstrated that, in yeast cells, it has an EC50 in the sub-micromolar range. PMID:15584743

  11. Evolution of Catalytic Stereoselective Olefin Metathesis: From Ancillary Transformation to Purveyor of Stereochemical Identity

    PubMed Central

    2015-01-01

    There have been numerous significant advances in catalytic olefin metathesis (OM) during the past two decades. Such progress has transformed this important set of reactions to strategically pivotal processes that generate stereochemical identity while delivering molecules that cannot be easily prepared by alternative routes. In this Perspective, an analysis of the origin of the inception of bidentate benzylidene ligands for Ru-based OM catalysts is first presented. This is followed by an overview of the intellectual basis that culminated in the development of Mo-based diolates and stereogenic-at-Ru complexes for enantioselective OM. The principles accrued from the study of the latter Ru carbenes and Mo alkylidenes and utilized in the design of stereogenic-at-Mo, -W, and -Ru species applicable to enantioselective and Z-selective OM are then discussed. The influence of the recently introduced catalytic OM protocols on the design of synthesis routes leading to complex organic molecules is probed. The impact of a better understanding of the mechanistic nuances of OM toward the discovery of stereoselective catalysts is reviewed as well. PMID:24720633

  12. The total synthesis of (-)-cryptocaryol A.

    PubMed

    Dias, L C; Kuroishi, P K; de Lucca, E C

    2015-03-28

    A stereoselective total synthesis of (-)-cryptocaryol A (1) is described. Key features of the 17-step route include the use of three boron-mediated aldol reaction-reduction sequences to control all stereocenters and an Ando modification of the Horner-Wadsworth-Emmons olefination that permitted the installation of the Z double bond of the α-pyrone ring. PMID:25695350

  13. Catalytic enantioselective synthesis of vicinal dialkyl arrays.

    PubMed

    van Zijl, Anthoni W; Szymanski, Wiktor; López, Ferrnando; Minnaard, Adriaan J; Feringa, Ben L

    2008-09-19

    With a consecutive "asymmetric allylic alkylation (AAA)/cross-metathesis (CM)/conjugate addition (CA)" protocol it is possible to synthesize either stereoisomer of compounds containing a vicinal dialkyl array with excellent stereoselectivity. The versatility of this protocol in natural product synthesis is demonstrated in the preparation of the ant pheromones faranal and lasiol. PMID:18683977

  14. Synthesis of pterostilbene by Julie Olefination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A simple, stereoselective route for the synthesis of the biologically active compounds trans-pterostilbene and tetramethoxy stilbene from the readily available starting materials 3,5-dimethoxy benzyl alcohol and 4-hydroxy benzaldehyde was developed using Julia olefination as a key reaction....

  15. Facile Synthesis of Porous Dendritic Bimetallic Platinum-Nickel Nanocrystals as Efficient Catalysts for the Oxygen Reduction Reaction.

    PubMed

    Eid, Kamel; Wang, Hongjing; Malgras, Victor; Alothman, Zeid Abdullah; Yamauchi, Yusuke; Wang, Liang

    2016-05-01

    Certain bimetallic nanocrystals (NCs) possess promising catalytic properties for electrochemical energy conversion. Herein, we report a facile method for the one-step synthesis of porous dendritic PtNi NCs in aqueous solution at room temperature that contrasts with the traditional multistep thermal decomposition approach. The dendritic PtNi NCs assembled by interconnected arms are efficient catalysts for the oxygen reduction reaction. This direct and efficient method is favorable for the up-scaled synthesis of active catalysts used in electrochemical applications. PMID:26879517

  16. Improved synthesis of (3E,7Z)-3,7-tetradecadienyl acetate, the major sex pheromone constituent of the potato pest Symmetrischema tangolias (Gyen).

    PubMed

    Ragoussis, Valentine; Perdikaris, Stamatis; Karamolegkos, Antonis; Magkiosi, Konstantina

    2008-12-24

    An efficient six-step synthesis of (3E,7Z)-3,7-tetradecadienyl acetate, the major component of the sex pheromone of the potato pest Symmetrischema tangolias (Gyen), is described, starting from the commercially available dihydropyran. The stereoselective formation of the 7Z double bond is accomplished by a Wittig reaction, while the 3E double bond is formed by a modified Knoevenagel condensation. The overall yield of the synthesis is 28%, giving the final product in high stereochemical purity (95%). The simplicity and the low cost of the herein reported synthesis suggest the potential practical use of the above pheromone in integrated management programs, for this serious insect pest. PMID:19053388

  17. Design and Synthesis of Novel Block Copolymers for Efficient Opto-Electronic Applications

    NASA Technical Reports Server (NTRS)

    Sun, Sam-Shajing; Fan, Zhen; Wang, Yiqing; Taft, Charles; Haliburton, James; Maaref, Shahin

    2002-01-01

    It has been predicted that nano-phase separated block copolymer systems containing electron rich donor blocks and electron deficient acceptor blocks may facilitate the charge carrier separation and migration in organic photovoltaic devices due to improved morphology in comparison to polymer blend system. This paper presents preliminary data describing the design and synthesis of a novel Donor-Bridge-Acceptor (D-B-A) block copolymer system for potential high efficient organic optoelectronic applications. Specifically, the donor block contains an electron donating alkyloxy derivatized polyphenylenevinylene (PPV), the acceptor block contains an electron withdrawing alkyl-sulfone derivatized polyphenylenevinylene (PPV), and the bridge block contains an electronically neutral non-conjugated aliphatic hydrocarbon chain. The key synthetic strategy includes the synthesis of each individual block first, then couple the blocks together. While the donor block stabilizes and facilitates the transport of the holes, the acceptor block stabilizes and facilitates the transport of the electrons, the bridge block is designed to hinder the probability of electron-hole recombination. Thus, improved charge separation and stability are expected with this system. In addition, charge migration toward electrodes may also be facilitated due to the potential nano-phase separated and highly ordered block copolymer ultra-structure.

  18. Efficient synthesis of ureas by direct palladium-catalyzed oxidative carbonylation of amines.

    PubMed

    Gabriele, Bartolo; Salerno, Giuseppe; Mancuso, Raffaella; Costa, Mirco

    2004-07-01

    A general synthesis of symmetrically disubstituted ureas and trisubstituted ureas by direct Pd-catalyzed oxidative carbonylation of primary amines or of a mixture of a primary and a secondary amine, respectively, with unprecedented catalytic efficiencies for this kind of process, is reported. Reactions are carried out at 90-100 degrees C in DME as the solvent in the presence of PdI(2) in conjunction with an excess of KI as the catalytic system and under 20 atm of a 4:1 mixture of CO and air. In some cases, working in the presence of an excess of CO(2) (40 atm) in addition to CO and air (60 atm total) had a beneficial effect on substrate reactivity and product yield. Cyclic five-membered and six-membered ureas were easily formed from primary diamines. The methodology has been successfully applied to the synthesis of pharmacologically active ureas, such as those deriving from alpha-amino esters or urea NPY5RA-972, a potent antagonist of the neuropeptide Y5 receptor. PMID:15230597

  19. Self-templated synthesis of novel carbon nanoarchitectures for efficient electrocatalysis

    PubMed Central

    Wu, Xi-Lin; Wen, Tao; Guo, Hong-Li; Liu, Shoujie; Wang, Xiangke; Xu, An-Wu; Mezger, Markus

    2016-01-01

    The cost-efficient large-scale production of novel carbon nanostructure with high performance is still a challenge, restricting their applications in catalysis. Herein, we present a low-cost one-pot and one-step approach for the synthesis of both N-doped graphene (NG) and N-doped carbon nanotubes (NCNTs) from self-templated organic nanoplates. By varying the FeCl3 concentration in the precursor, we can control the formation of graphene or CNTs. To the best of our knowledge, this is the first example for the controllable synthesis of graphene or CNTs by varying the precursors’ compositions. This provides a simple and cost-effective route for the large-scale production of both NG and NCNTs for applications in catalysis. By example, we show how these unique structured nanocarbons can be applied in electrocatalysis for oxygen reduction reaction (ORR). The obtained NG and NCNTs show excellent ORR activities with long-term stability under alkaline conditions. The unique porous nanostructure, abundant defects, homogeneous N-doping and high N-content in the NG and NCNTs can provide abundant active sites, leading to the excellent ORR performance. This research not only displayed a simple and cost-effective approach for the large-scale production of novel carbon nanoarchitectures, but also revealed the exceptional application potential of these nanocarbons for electrocatalysis. PMID:27301537

  20. Self-templated synthesis of novel carbon nanoarchitectures for efficient electrocatalysis

    NASA Astrophysics Data System (ADS)

    Wu, Xi-Lin; Wen, Tao; Guo, Hong-Li; Liu, Shoujie; Wang, Xiangke; Xu, An-Wu; Mezger, Markus

    2016-06-01

    The cost-efficient large-scale production of novel carbon nanostructure with high performance is still a challenge, restricting their applications in catalysis. Herein, we present a low-cost one-pot and one-step approach for the synthesis of both N-doped graphene (NG) and N-doped carbon nanotubes (NCNTs) from self-templated organic nanoplates. By varying the FeCl3 concentration in the precursor, we can control the formation of graphene or CNTs. To the best of our knowledge, this is the first example for the controllable synthesis of graphene or CNTs by varying the precursors’ compositions. This provides a simple and cost-effective route for the large-scale production of both NG and NCNTs for applications in catalysis. By example, we show how these unique structured nanocarbons can be applied in electrocatalysis for oxygen reduction reaction (ORR). The obtained NG and NCNTs show excellent ORR activities with long-term stability under alkaline conditions. The unique porous nanostructure, abundant defects, homogeneous N-doping and high N-content in the NG and NCNTs can provide abundant active sites, leading to the excellent ORR performance. This research not only displayed a simple and cost-effective approach for the large-scale production of novel carbon nanoarchitectures, but also revealed the exceptional application potential of these nanocarbons for electrocatalysis.

  1. Highly Efficient Synthesis of an Emerging Lipophilic Antioxidant: 2-Ethylhexyl Ferulate.

    PubMed

    Huang, Kuo-Chuan; Li, Ying; Kuo, Chia-Hung; Twu, Yawo-Kuo; Shieh, Chwen-Jen

    2016-01-01

    Ferulic acid in ester form has shown a stronger ability in ameliorating certain pathological conditions and inhibiting lipid oxidation. In present study, a solvent-free and reduced pressure evaporation system was developed for lipase-catalyzed synthesis of 2-ethylhexyl ferulate (2-EF) from ferulic acid and 2-ethylhexanol. A Box-Behnken design with response surface methodology (RSM) and artificial neural network (ANN) was selected to model and optimize the process. Based on the yields of 2-EF, reaction temperature was shown to be the most important process factor on the molar conversion among all variables. The residual values and the coefficient of determination (R²) calculated from the design data indicated that ANN was better than RSM in data fitting. Overall, the present lipase-catalyzed approach for 2-EF synthesis at low reaction temperature in a reduced pressure evaporation system shows high 2-EF production efficiency. Notably, this approach can reduce the enzyme denaturation and ferulic acid oxidation that usually occur during long-term biosynthetic operations at high temperature. PMID:27077838

  2. Self-templated synthesis of novel carbon nanoarchitectures for efficient electrocatalysis.

    PubMed

    Wu, Xi-Lin; Wen, Tao; Guo, Hong-Li; Liu, Shoujie; Wang, Xiangke; Xu, An-Wu; Mezger, Markus

    2016-01-01

    The cost-efficient large-scale production of novel carbon nanostructure with high performance is still a challenge, restricting their applications in catalysis. Herein, we present a low-cost one-pot and one-step approach for the synthesis of both N-doped graphene (NG) and N-doped carbon nanotubes (NCNTs) from self-templated organic nanoplates. By varying the FeCl3 concentration in the precursor, we can control the formation of graphene or CNTs. To the best of our knowledge, this is the first example for the controllable synthesis of graphene or CNTs by varying the precursors' compositions. This provides a simple and cost-effective route for the large-scale production of both NG and NCNTs for applications in catalysis. By example, we show how these unique structured nanocarbons can be applied in electrocatalysis for oxygen reduction reaction (ORR). The obtained NG and NCNTs show excellent ORR activities with long-term stability under alkaline conditions. The unique porous nanostructure, abundant defects, homogeneous N-doping and high N-content in the NG and NCNTs can provide abundant active sites, leading to the excellent ORR performance. This research not only displayed a simple and cost-effective approach for the large-scale production of novel carbon nanoarchitectures, but also revealed the exceptional application potential of these nanocarbons for electrocatalysis. PMID:27301537

  3. Efficient synthesis and antioxidant evaluation of 2-aryl-3-(pyrimidin-2-yl)-thiazolidinones.

    PubMed

    Campos Júnior, José C; Gouvêa, Daniela P; Ribeiro, Camila da S; Dutra, Filipe S P; Stefanello, Francieli M; Pereira, Claudio M P; Cunico, Wilson; Siqueira, Geonir M

    2013-09-01

    In the present study, we reported the efficient synthesis of 11 3-(pyrimidin-2-yl)-thiazolidinones in good yields using molecular sieve as the desiccant agent. In addition, we have evaluated the antioxidant capacity of the synthesized compounds by the 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH•) and the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS(+•) ) radicals scavenging assay. Six compounds showed antioxidant activity towards DPPH• (EC50 between 16.13 and 49.94 µg/mL) and also demonstrated excellent activity regarding ABTS(+•) (TEAC: 10.32-53.52). These results showed that compounds 3-(pyrimidin-2-yl)-thiazolidinones may be easily synthesized by a less expensive procedure and could be a good starting point to the development of new antioxidant compounds. PMID:23798366

  4. Synthesis of WS2 Nanowires as Efficient 808 nm-Laser-Driven Photothermal Nanoagents.

    PubMed

    Macharia, Daniel K; Yu, Nuo; Zhong, Runzhi; Xiao, Zhiyin; Yang, Jianmao; Chen, Zhigang

    2016-06-01

    A prerequisite for the development of photothermal ablation therapy for cancer is to obtain efficient photothermal nanoagents that can be irradiated by near-infrared (NIR) laser. Herein, we have reported the synthesis of WS2 nanowires as photothermal nanoagents by the reaction of WCl6 with CS2 in oleylamine at 280 degrees C. WS2 nanowires have the thickness of -2 nm and length of -100 nm. Importantly, the chloroform dispersion of WS2 nanowires exhibits strong photoabsorption in NIR region. The temperature of the dispersion (0.10-0.50 mg/mL) can increase by 12.8-23.9 degrees C in 5 min under the irradiation of 808 nm laser with a power density of 0.80 W/cm2. Therefore, WS2 nanowires have a great superiority as a new nanoagent for NIR-induced photothermal ablation of cancer, due to their small size and excellent photothermal performance. PMID:27427645

  5. Efficient assembly of threaded molecular machines for sequence-specific synthesis.

    PubMed

    De Bo, Guillaume; Kuschel, Sonja; Leigh, David A; Lewandowski, Bartosz; Papmeyer, Marcus; Ward, John W

    2014-04-16

    We report on an improved strategy for the preparation of artificial molecular machines that can pick up and assemble reactive groups in sequence by traveling along a track. In the new approach a preformed rotaxane synthon is attached to the end of an otherwise fully formed strand of building blocks. This "rotaxane-capping" protocol is significantly more efficient than the "final-step-threading" method employed previously and enables the synthesis of threaded molecular machines that operate on extended oligomer, and potentially polymer, tracks. The methodology is exemplified through the preparation of a machine that adds four amino acid building blocks from a strand in sequence, featuring up to 20-membered ring native chemical ligation transition states. PMID:24678971

  6. Efficient and scalable synthesis of α,α-disubstituted β-amino amides.

    PubMed

    Paulsen, Marianne Hagensen; Engqvist, Magnus; Ausbacher, Dominik; Strøm, Morten Bøhmer; Bayer, Annette

    2016-08-21

    A practical and efficient methodology for the preparation of 2-aminoethyl α,α-disubstituted β-amino amides in three steps from methyl cyanoacetate has been developed. The key step in the synthesis was the chemoselective reduction of the nitrile group in presence of an amide and aryl halide functionalities. Reduction with RANEY® Nickel catalyst, either with molecular hydrogen (8-10 bar) or under transfer hydrogenation conditions, necessitated in situ protection of the resulting amines with Boc2O, whereas aryl bromide containing nitriles could be chemoselectively reduced with ZnCl2/NaBH4 without debromination. The developed protocol involved only one chromatographic purification step and can be performed at gram scale. PMID:27439743

  7. Rapid Synthesis of Cobalt Nitride Nanowires: Highly Efficient and Low-Cost Catalysts for Oxygen Evolution.

    PubMed

    Zhang, Yongqi; Ouyang, Bo; Xu, Jing; Jia, Guichong; Chen, Shi; Rawat, Rajdeep Singh; Fan, Hong Jin

    2016-07-18

    Electrochemical splitting of water to produce hydrogen and oxygen is an important process for many energy storage and conversion devices. Developing efficient, durable, low-cost, and earth-abundant electrocatalysts for the oxygen evolution reaction (OER) is of great urgency. To achieve the rapid synthesis of transition-metal nitride nanostructures and improve their electrocatalytic performance, a new strategy has been developed to convert cobalt oxide precursors into cobalt nitride nanowires through N2 radio frequency plasma treatment. This method requires significantly shorter reaction times (about 1 min) at room temperature compared to conventional high-temperature NH3 annealing which requires a few hours. The plasma treatment significantly enhances the OER activity, as evidenced by a low overpotential of 290 mV to reach a current density of 10 mA cm(-2) , a small Tafel slope, and long-term durability in an alkaline electrolyte. PMID:27254484

  8. ACCESS 3. Approximation concepts code for efficient structural synthesis: User's guide

    NASA Technical Reports Server (NTRS)

    Fleury, C.; Schmit, L. A., Jr.

    1980-01-01

    A user's guide is presented for ACCESS-3, a research oriented program which combines dual methods and a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and dual algorithms of mathematical programming are applied in the design optimization procedure. This program retains all of the ACCESS-2 capabilities and the data preparation formats are fully compatible. Four distinct optimizer options were added: interior point penalty function method (NEWSUMT); second order primal projection method (PRIMAL2); second order Newton-type dual method (DUAL2); and first order gradient projection-type dual method (DUAL1). A pure discrete and mixed continuous-discrete design variable capability, and zero order approximation of the stress constraints are also included.

  9. Design, synthesis and biological studies of efficient multivalent melanotropin ligands: tools towards melanoma diagnosis and treatment

    PubMed Central

    Brabez, Nabila; Lynch, Ronald M.; Xu, Liping; Gillies, Robert J.; Chassaing, Gerard; Lavielle, Solange; Hruby, Victor J.

    2011-01-01

    In order to achieve early detection and specific cancer treatment we propose the use of multivalent interactions in which a series of binding events leads to increased affinity and consequently to selectivity. Using melanotropin (MSH) ligands, our aim is to target melanoma cells, which overexpress melanocortin receptors. In this study, we report the design and efficient synthesis of new trivalent ligands bearing MSH ligands. Evaluation of these multimers on a cell model engineered to overexpress melanocortin 4 receptors (MC4R) showed up to a 350-fold increase in binding compared to the monomer, resulting in a trivalent construct with nanomolar affinity starting from a micromolar affinity ligand. Cyclic adenosine monophosphate (cAMP) production was also investigated leading to more insights into the effects of multivalent compounds on transduction mechanisms. PMID:21928837

  10. Microfluidic Directed Synthesis of Alginate Nanogels with Tunable Pore Size for Efficient Protein Delivery.

    PubMed

    Bazban-Shotorbani, Salime; Dashtimoghadam, Erfan; Karkhaneh, Akbar; Hasani-Sadrabadi, Mohammad Mahdi; Jacob, Karl I

    2016-05-17

    Alginate is a biopolymer with favorable pH-sensitive properties for oral delivery of peptides and proteins. However, conventional alginate nanogels have limitations such as low encapsulation efficiency because of drug leaching during bead preparation and burst release in high pH values. These shortcomings originate from large pore size of the nanogels. In this work, we proposed an on-chip hydrodynamic flow focusing approach for synthesis of alginate nanogels with adjustable pore size to achieve fine-tunable release profile of the encapsulated bioactive agents. It is demonstrated that the microstructure of nanogels can be controlled through adjusting flow ratio and mixing time directed on microfluidic platforms consisting of cross-junction microchannels. In this study, the average pore size of alginate nanogels (i.e., average molecular weight between cross-links, Mc) was related to synthesis parameters. Mc was calculated from equations based on equilibrium swelling theory and proposed methods to modify the theory for pH-sensitive nanogels. In the equations we derived, size and compactness of nanogels are key factors, which can be adjusted by controlling the flow ratio. It was found that increase in flow ratio increases the size of nanogels and decreases their compactness. The size of on-chip generated nanogels for flow ratio of 0.02-0.2 was measured to be in the range of 68-138 nm. Moreover, a method based on the Mie theory was implemented to estimate the aggregation number (Nagg) of polymer chains inside the nanogels as an indicator of compactness. According to the size and compactness results along with equations of modified swelling theory, Mc obtained to be in the range of 0.5-0.8 kDa. The proposed method could be considered as a promising approach for efficient polypeptides encapsulation and their sustained release. PMID:26938744

  11. Total Synthesis and Structural Revision of Vannusals A and B. Synthesis of the True Structures of Vannusals A and B

    PubMed Central

    Ortiz, Adrian; Zhang, Hongjun; Guella, Graziano

    2010-01-01

    Having determined, through total synthesis, that the originally assigned structure of vannusals A and B were incorrect, we set out to uncover the identity of the true structures of these novel marine natural products. Our search was based on intelligence gathered by NMR spectroscopy and chemical synthesis and took us through the total synthesis of eight diastereomeric vannusal B structures [2, d-2, 3, d-3, 4, d-4, 5, and d-5, Figure 1]. The true structures of vannusals A and B were finally determined to be d-5 and d-1, respectively. Their total synthesis was based on a highly convergent and efficient strategy that involved fragments vinyl iodide (−)-6 and aldehyde (±)-94, and featured a stereoselective lithium-mediated coupling reaction and a samarium-induced cyclization process that forged the final ring of the carbon framework. The synthetic strategies and technologies developed in these investigations expand the scope of chemical synthesis and render these compounds readily available for biological evaluation, while the NMR spectroscopic insights gained should prove useful in future structural determination endeavors. PMID:20443558

  12. Aromatic Interactions as Control Elements in Stereoselective Organic Reactions

    PubMed Central

    2012-01-01

    Conspectus This Account describes how attractive interaction of aromatic rings with other groups can influence and control the stereoselectivity of many reactions. Recent developments in theory have led to improved accuracy in the modeling of aromatic interactions. Quantum mechanical modeling can now provide insights into the roles of these interactions at a level of detail not previously accessible, both for ground-state species and for transition states of chemical reactions. In this Account, we show how transition-state modeling led to the discovery of the influence of aryl groups on the stereoselectivities of several types of organic reactions. These reaction types include asymmetric dihydroxylations, transfer hydrogenations, hetero-Diels–Alder reactions, acyl transfers, and Claisen rearrangements. Our recent studies have led to a novel mechanistic picture for two classes of (4+3) cycloadditions, both of which involve reactions of furans with oxyallyl intermediates. The first class of cycloadditions, developed by Hsung, features neutral oxyallyls containing a chiral oxazolidinone auxiliary. Originally, these cycloadditions were thought rely on differential steric crowding of the two faces of a planar intermediate. Computations reveal a different picture and show that cycloadditions with furan takes place preferentially through the more crowded transition state, with furan adding on the same side as the oxazolidinone’s Ph substituent. The crowded transition state is stabilized by a CH–π interaction between furan and Ph, worth about 2.0 kcal/mol. Stereocontrol in a second class of (4+3) cycloadditions, involving chiral alkoxy siloxyallyl cations, also is controlled by attractive interactions with aromatic rings. Alkoxy groups derived from chiral α-methylbenzyl alcohols are found to favor crowded transition states, where a CH–π interaction is again present between furan and Ar. The cationic cycloadditions are stepwise, while the Hsung cycloadditions are

  13. The Yeast Mitochondrial RNA Polymerase and Transcription Factor Complex Catalyzes Efficient Priming of DNA Synthesis on Single-stranded DNA.

    PubMed

    Ramachandran, Aparna; Nandakumar, Divya; Deshpande, Aishwarya P; Lucas, Thomas P; R-Bhojappa, Ramanagouda; Tang, Guo-Qing; Raney, Kevin; Yin, Y Whitney; Patel, Smita S

    2016-08-01

    Primases use single-stranded (ss) DNAs as templates to synthesize short oligoribonucleotide primers that initiate lagging strand DNA synthesis or reprime DNA synthesis after replication fork collapse, but the origin of this activity in the mitochondria remains unclear. Herein, we show that the Saccharomyces cerevisiae mitochondrial RNA polymerase (Rpo41) and its transcription factor (Mtf1) is an efficient primase that initiates DNA synthesis on ssDNA coated with the yeast mitochondrial ssDNA-binding protein, Rim1. Both Rpo41 and Rpo41-Mtf1 can synthesize short and long RNAs on ssDNA template and prime DNA synthesis by the yeast mitochondrial DNA polymerase Mip1. However, the ssDNA-binding protein Rim1 severely inhibits the RNA synthesis activity of Rpo41, but not the Rpo41-Mtf1 complex, which continues to prime DNA synthesis efficiently in the presence of Rim1. We show that RNAs as short as 10-12 nt serve as primers for DNA synthesis. Characterization of the RNA-DNA products shows that Rpo41 and Rpo41-Mtf1 have slightly different priming specificity. However, both prefer to initiate with ATP from short priming sequences such as 3'-TCC, TTC, and TTT, and the consensus sequence is 3'-Pu(Py)2-3 Based on our studies, we propose that Rpo41-Mtf1 is an attractive candidate for serving as the primase to initiate lagging strand DNA synthesis during normal replication and/or to restart stalled replication from downstream ssDNA. PMID:27311715

  14. Micelle-Template Synthesis of Nitrogen-Doped Mesoporous Graphene as an Efficient Metal-Free Electrocatalyst for Hydrogen Production

    PubMed Central

    Huang, Xiaodan; Zhao, Yufei; Ao, Zhimin; Wang, Guoxiu

    2014-01-01

    Synthesis of mesoporous graphene materials by soft-template methods remains a great challenge, owing to the poor self-assembly capability of precursors and the severe agglomeration of graphene nanosheets. Herein, a micelle-template strategy to prepare porous graphene materials with controllable mesopores, high specific surface areas and large pore volumes is reported. By fine-tuning the synthesis parameters, the pore sizes of mesoporous graphene can be rationally controlled. Nitrogen heteroatom doping is found to remarkably render electrocatalytic properties towards hydrogen evolution reactions as a highly efficient metal-free catalyst. The synthesis strategy and the demonstration of highly efficient catalytic effect provide benchmarks for preparing well-defined mesoporous graphene materials for energy production applications. PMID:25523276

  15. Micelle-Template Synthesis of Nitrogen-Doped Mesoporous Graphene as an Efficient Metal-Free Electrocatalyst for Hydrogen Production

    NASA Astrophysics Data System (ADS)

    Huang, Xiaodan; Zhao, Yufei; Ao, Zhimin; Wang, Guoxiu

    2014-12-01

    Synthesis of mesoporous graphene materials by soft-template methods remains a great challenge, owing to the poor self-assembly capability of precursors and the severe agglomeration of graphene nanosheets. Herein, a micelle-template strategy to prepare porous graphene materials with controllable mesopores, high specific surface areas and large pore volumes is reported. By fine-tuning the synthesis parameters, the pore sizes of mesoporous graphene can be rationally controlled. Nitrogen heteroatom doping is found to remarkably render electrocatalytic properties towards hydrogen evolution reactions as a highly efficient metal-free catalyst. The synthesis strategy and the demonstration of highly efficient catalytic effect provide benchmarks for preparing well-defined mesoporous graphene materials for energy production applications.

  16. Evaluation of an automated double-synthesis module: efficiency and reliability of subsequent radiosyntheses of FHBG and FLT.

    PubMed

    Niedermoser, Sabrina; Pape, Manuela; Gildehaus, Franz Josef; Wängler, Carmen; Hartenbach, Markus; Schirrmacher, Ralf; Bartenstein, Peter; Wängler, Björn

    2012-05-01

    We optimized the synthesis methods for 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) and 9-(4-[(18)F]fluoro-3-[hydroxymethyl]butyl)guanine) ([(18)F]FHBG) and automated them on an Explora General Nucleophilic double-synthesis module. Furthermore, the synthesis efficiency and reliability and the formation of cross-contaminations of the products when preparing two consecutive batches were evaluated. Whereas the preinstalled FLT synthesis conditions required substantial modification in reaction and neutralization conditions to achieve radiochemical yields of up to 60% within 70±10 min including high-performance liquid chromatography purification, the synthesis of FHBG had to be implemented to the module to obtain competitive radiochemical yields of up to 40% in an overall synthesis time of 60±10 min. The radiochemical purities obtained were ≥99% and ≥96% for the synthesis of [(18)F]FLT and [(18)F]FHBG, respectively. No significant changes in yield or purity could be observed between both batch productions. We found that the yields and purities also did not change when performing FLT after FHBG syntheses and vice versa. Hence, we developed a synthesis setup that offers the opportunity to perform two subsequent syntheses of either [(18)F]FLT, [(18)F]FHBG or [(18)F]FLT after [(18)F]FHBG without decrease in radiochemical yields and purities. Also, no cross-contaminations were observed, which can be attributed to the use of separate product delivery tubes, purification columns and an automated intermediate cleaning program. These results open up the possibility of producing consecutively either two equal (18)F-fluorinated tracers or two different ones in high yields on the same synthesis module. PMID:22172393

  17. Rapid and efficient synthesis of 4(3H)-quinazolinones under ultrasonic irradiation using silica-supported Preyssler nanoparticles.

    PubMed

    Heravi, Majid M; Sadjadi, Samaheh; Sadjadi, Sodeh; Oskooie, Hossein A; Bamoharram, Fatemeh F

    2009-08-01

    A new synthesis of 4(3H)-quinazolinone from the reaction of 2-amino-benzamide, and acylchlorides in the presence of catalytic amounts of silica-supported Preyssler nano particles as green, reusable and efficient catalyst under ultra sonic irradiation is reported. PMID:19362508

  18. A stepwise bulk-to-cluster-to-particle transformation toward the efficient synthesis of alkynyl-protected silver nanoclusters.

    PubMed

    Guo, Hui; He, Xin; Wan, Chong-Qing; Zhao, Liang

    2016-06-01

    We report herein the efficient synthesis of alkynyl-protected silver nanoclusters in terms of macrocycle-assisted bulk-to-cluster-to-nanoparticle transformation. Different substituted phenylacetylide ligands are applied to stabilize the silver nanoclusters by metal-carbon bonds and meanwhile determine the size of silver nanoclusters. PMID:27241312

  19. Cyanuric Chloride as an Efficient Catalyst for the Synthesis of 2,3-Unsaturated O-Glycosides by Ferrier Rearrangement

    PubMed Central

    Yang, Xiaojuan; Li, Na

    2014-01-01

    Cyanuric chloride has been found to be an efficient catalyst for the synthesis of 2,3-unsaturated O-glycosides from the reaction of 3,4,6-tri-O-acetyl-D-glucal and a wide range of alcohols in dichloromethane at room temperature. The experimental procedure is simple, and the products are obtained in high yields. PMID:24574881

  20. One-pot atom-efficient synthesis of bio-renewable polyesters and cyclic carbonates through tandem catalysis.

    PubMed

    Jia, Fan; Chen, Xiaoyu; Zheng, Yan; Qin, Yusheng; Tao, Youhua; Wang, Xianhong

    2015-05-18

    One-pot synthesis of well-defined bio-renewable polyesters and cyclic carbonates in high yields was successfully realized for the first time by way of a tandem reaction using metal salen complexes as catalysts. This tandem process offered unprecedented opportunities for the atom-efficient production of two relevant compounds. PMID:25892206

  1. Highly efficient one-pot three-component synthesis of naphthopyran derivatives in water catalyzed by hydroxyapatite

    EPA Science Inventory

    An expeditious and efficient protocol for the synthesis of naphthopyrans has been developed that proceeds via one-pot three-component sequential reaction in water catalyzed by hydroxyapatite or sodium-modified-hydroxyapatite. The title compounds have been obtained in high yield a...

  2. AN EFFICIENT AND SIMPLE AQUEOUS N-HETEROCYCLIZATION OF ANILINE DERIVATIVES: MICROWAVE-ASSISTED SYNTHESIS OF N-ARYL AZACYCLOALKANES

    EPA Science Inventory

    An efficient and clean synthesis of N-aryl azacycloalkanes from alkyl dihalides and aniline derivatives has been achieved using microwave irradiation in an aqueous potassium carbonate medium. The phase separation can simplify the product isolation and reduce usage of vol...

  3. Stereoselective interaction between the R enantiomer of warfarin and cimetidine.

    PubMed Central

    Choonara, I A; Cholerton, S; Haynes, B P; Breckenridge, A M; Park, B K

    1986-01-01

    The stereoselectivity of the pharmacokinetic interaction between warfarin and cimetidine was investigated in eight healthy volunteers. The warfarin enantiomers were given separately as single doses (15 mg) alone and during chronic administration of cimetidine (1 g day-1). Cimetidine did not interact with S warfarin but there was an interaction with the R enantiomer of warfarin. Cimetidine caused a significant increase in the mean plasma half-life of R warfarin (from 47.8 h to 57.8 h) and a significant decrease in its mean plasma clearance (from 2.3 to 1.7 ml h-1 kg-1) (P less than 0.02). Administration of a pharmacological dose of vitamin K1 together with the enantiomers of warfarin was necessary clinically and resulted in elevation of vitamin K1 2,3-epoxide concentrations, which were similar in each case. PMID:2938614

  4. Phase chirality and stereo-selective swelling of cholesteric elastomers

    NASA Astrophysics Data System (ADS)

    Courty, S.; Tajbakhsh, A. R.; Terentjev, E. M.

    2003-12-01

    Cholesteric elastomers possess a macroscopic “phase chirality” as the director n rotates in a helical fashion along an optical axis z and can be described by a chiral order parameter α. This parameter can be tuned by changing the helix pitch p and the elastic properties of the network at formation. The cholesterics also possess a local nematic order, changing with temperature or during solvent swelling. In this paper, by measuring the power of optical rotation d Psi/d z, we discover how these two parameters vary as functions of temperature or solvent adsorbed by the network. The main result is a finding of pronounced stereo-selectivity of cholesteric elastomers, demonstrating itself in the retention of the “correct” chirality component of a racemic solvent. It has been possible to quantify the amount of such stereo-separation, and the basic dynamics of the effect.

  5. Stereoselective Inhibition of the hERG1 Potassium Channel

    PubMed Central

    Grilo, Liliana Sintra; Carrupt, Pierre-Alain; Abriel, Hugues

    2010-01-01

    A growing number of drugs have been shown to prolong cardiac repolarization, predisposing individuals to life-threatening ventricular arrhythmias known as Torsades de Pointes. Most of these drugs are known to interfere with the human ether à-gogo related gene 1 (hERG1) channel, whose current is one of the main determinants of action potential duration. Prolonged repolarization is reflected by lengthening of the QT interval of the electrocardiogram, as seen in the suitably named drug-induced long QT syndrome. Chirality (presence of an asymmetric atom) is a common feature of marketed drugs, which can therefore exist in at least two enantiomers with distinct three-dimensional structures and possibly distinct biological fates. Both the pharmacokinetic and pharmacodynamic properties can differ between enantiomers, as well as also between individuals who take the drug due to metabolic polymorphisms. Despite the large number of reports about drugs reducing the hERG1 current, potential stereoselective contributions have only been scarcely investigated. In this review, we present a non-exhaustive list of clinically important molecules which display chiral toxicity that may be related to hERG1-blocking properties. We particularly focus on methadone cardiotoxicity, which illustrates the importance of the stereoselective effect of drug chirality as well as individual variations resulting from pharmacogenetics. Furthermore, it seems likely that, during drug development, consideration of chirality in lead optimization and systematic assessment of the hERG1 current block with all enantiomers could contribute to the reduction of the risk of drug-induced LQTS. PMID:21833176

  6. Efficient Catalytic Activity BiFeO3 Nanoparticles Prepared by Novel Microwave-Assisted Synthesis.

    PubMed

    Zou, Jing; Gong, Wanyun; Ma, Jinai; Li, Lu; Jiang, Jizhou

    2015-02-01

    A novel microwave-assisted sol-gel method was applied to the synthesis of the single-phase perovskite bismuth ferrite nanoparticles (BFO NPs) with the mean diameter ca. 73.7 nm. The morphology was characterized by scanning electron microscope (SEM). The X-ray diffraction (XRD) revealed the rhombohedral phase with R3c space group. The weak ferromagnetic behavior at room temperature was affirmed by the vibrating sample magnetometer (VSM). According to the UV-vis diffuse reflectance spectrum (UV-DSR), the band gap energy of BFO NPs was determined to be 2.18 eV. The electrochemical activity was evaluated by BFO NPs-chitosan-glassy carbon electrode (BFO-CS-GCE) sensor for detection of p-nitrophenol contaminants. The material showed an efficient oxidation catalytic activity by degrading methylene blue (MB). It was found that the degradation efficiency of 10 mg L-1 MB at pH 6.0 was above 90.9% after ultrasound- and microwave-combined-assisted (US-MW) irradiation for 15 min with BFO NPs as catalyst and H202 as oxidant. A possible reaction mechanism of degradation of MB was also proposed. PMID:26353647

  7. Identification of a critical determinant that enables efficient fatty acid synthesis in oleaginous fungi

    PubMed Central

    Chen, Haiqin; Hao, Guangfei; Wang, Lei; Wang, Hongchao; Gu, Zhennan; Liu, Liming; Zhang, Hao; Chen, Wei; Chen, Yong Q.

    2015-01-01

    Microorganisms are valuable resources for lipid production. What makes one microbe but not the other able to efficiently synthesize and accumulate lipids is poorly understood. In the present study, global gene expression prior to and after the onset of lipogenesis was determined by transcriptomics using the oleaginous fungus Mortierella alpina as a model system. A core of 23 lipogenesis associated genes was identified and their expression patterns shared a high similarity among oleaginous microbes Chlamydomonas reinhardtii, Mucor circinelloides and Rhizopus oryzae but was dissimilar to the non-oleaginous Aspergillus nidulans. Unexpectedly, Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) in the pentose phosphate pathway (PPP) were found to be the NADPH producers responding to lipogenesis in the oleaginous microbes. Their role in lipogenesis was confirmed by a knockdown experiment. Our results demonstrate, for the first time, that the PPP plays a significant role during fungal lipogenesis. Up-regulation of NADPH production by the PPP, especially G6PD, may be one of the critical determinants that enables efficiently fatty acid synthesis in oleaginous microbes. PMID:26059272

  8. Identification of a critical determinant that enables efficient fatty acid synthesis in oleaginous fungi.

    PubMed

    Chen, Haiqin; Hao, Guangfei; Wang, Lei; Wang, Hongchao; Gu, Zhennan; Liu, Liming; Zhang, Hao; Chen, Wei; Chen, Yong Q

    2015-01-01

    Microorganisms are valuable resources for lipid production. What makes one microbe but not the other able to efficiently synthesize and accumulate lipids is poorly understood. In the present study, global gene expression prior to and after the onset of lipogenesis was determined by transcriptomics using the oleaginous fungus Mortierella alpina as a model system. A core of 23 lipogenesis associated genes was identified and their expression patterns shared a high similarity among oleaginous microbes Chlamydomonas reinhardtii, Mucor circinelloides and Rhizopus oryzae but was dissimilar to the non-oleaginous Aspergillus nidulans. Unexpectedly, Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) in the pentose phosphate pathway (PPP) were found to be the NADPH producers responding to lipogenesis in the oleaginous microbes. Their role in lipogenesis was confirmed by a knockdown experiment. Our results demonstrate, for the first time, that the PPP plays a significant role during fungal lipogenesis. Up-regulation of NADPH production by the PPP, especially G6PD, may be one of the critical determinants that enables efficiently fatty acid synthesis in oleaginous microbes. PMID:26059272

  9. Efficient Synthesis of Peptide and Protein Functionalized Pyrrole-Imidazole Polyamides Using Native Chemical Ligation

    PubMed Central

    Janssen, Brian M. G.; van Ommeren, Sven P. F. I.; Merkx, Maarten

    2015-01-01

    The advancement of DNA-based bionanotechnology requires efficient strategies to functionalize DNA nanostructures in a specific manner with other biomolecules, most importantly peptides and proteins. Common DNA-functionalization methods rely on laborious and covalent conjugation between DNA and proteins or peptides. Pyrrole-imidazole (Py–Im) polyamides, based on natural minor groove DNA-binding small molecules, can bind to DNA in a sequence specific fashion. In this study, we explore the use of Py–Im polyamides for addressing proteins and peptides to DNA in a sequence specific and non-covalent manner. A generic synthetic approach based on native chemical ligation was established that allows efficient conjugation of both peptides and recombinant proteins to Py–Im polyamides. The effect of Py–Im polyamide conjugation on DNA binding was investigated by Surface Plasmon Resonance (SPR). Although the synthesis of different protein-Py–Im-polyamide conjugates was successful, attenuation of DNA affinity was observed, in particular for the protein-Py–Im-polyamide conjugates. The practical use of protein-Py–Im-polyamide conjugates for addressing DNA structures in an orthogonal but non-covalent manner, therefore, remains to be established. PMID:26053396

  10. An Efficient Synthesis Strategy for Metal-Organic Frameworks: Dry-Gel Synthesis of MOF-74 Framework with High Yield and Improved Performance.

    PubMed

    Das, Atanu Kumar; Vemuri, Rama Sesha; Kutnyakov, Igor; McGrail, B Peter; Motkuri, Radha Kishan

    2016-01-01

    Vapor-assisted dry-gel synthesis of the metal-organic framework-74 (MOF-74) structure, specifically Ni-MOF-74 produced from synthetic precursors using an organic-water hybrid solvent system, showed a very high yield (>90% with respect to 2,5-dihydroxyterepthalic acid) and enhanced performance. The Ni-MOF-74 obtained showed improved sorption characteristics towards CO2 and the refrigerant fluorocarbon dichlorodifluoromethane. Unlike conventional synthesis, which takes 72 hours using the tetrahydrofuran-water system, this kinetic study showed that Ni-MOF-74 forms within 12 hours under dry-gel conditions with similar performance characteristics, and exhibits its best performance characteristics even after 24 hours of heating. In the dry-gel conversion method, the physical separation of the solvent and precursor mixture allows for recycling of the solvent. We demonstrated efficient solvent recycling (up to three times) that resulted in significant cost benefits. The scaled-up manufacturing cost of Ni-MOF-74 synthesized via our dry-gel method is 45% of conventional synthesis cost. Thus, for bulk production of the MOFs, the proposed vapor-assisted, dry-gel method is efficient, simple, and inexpensive when compared to the conventional synthesis method. PMID:27306598

  11. An Efficient Synthesis Strategy for Metal-Organic Frameworks: Dry-Gel Synthesis of MOF-74 Framework with High Yield and Improved Performance

    NASA Astrophysics Data System (ADS)

    Das, Atanu Kumar; Vemuri, Rama Sesha; Kutnyakov, Igor; McGrail, B. Peter; Motkuri, Radha Kishan

    2016-06-01

    Vapor-assisted dry-gel synthesis of the metal-organic framework-74 (MOF-74) structure, specifically Ni-MOF-74 produced from synthetic precursors using an organic-water hybrid solvent system, showed a very high yield (>90% with respect to 2,5-dihydroxyterepthalic acid) and enhanced performance. The Ni-MOF-74 obtained showed improved sorption characteristics towards CO2 and the refrigerant fluorocarbon dichlorodifluoromethane. Unlike conventional synthesis, which takes 72 hours using the tetrahydrofuran-water system, this kinetic study showed that Ni-MOF-74 forms within 12 hours under dry-gel conditions with similar performance characteristics, and exhibits its best performance characteristics even after 24 hours of heating. In the dry-gel conversion method, the physical separation of the solvent and precursor mixture allows for recycling of the solvent. We demonstrated efficient solvent recycling (up to three times) that resulted in significant cost benefits. The scaled-up manufacturing cost of Ni-MOF-74 synthesized via our dry-gel method is 45% of conventional synthesis cost. Thus, for bulk production of the MOFs, the proposed vapor-assisted, dry-gel method is efficient, simple, and inexpensive when compared to the conventional synthesis method.

  12. An Efficient Synthesis Strategy for Metal-Organic Frameworks: Dry-Gel Synthesis of MOF-74 Framework with High Yield and Improved Performance

    PubMed Central

    Das, Atanu Kumar; Vemuri, Rama Sesha; Kutnyakov, Igor; McGrail, B. Peter; Motkuri, Radha Kishan

    2016-01-01

    Vapor-assisted dry-gel synthesis of the metal-organic framework-74 (MOF-74) structure, specifically Ni-MOF-74 produced from synthetic precursors using an organic-water hybrid solvent system, showed a very high yield (>90% with respect to 2,5-dihydroxyterepthalic acid) and enhanced performance. The Ni-MOF-74 obtained showed improved sorption characteristics towards CO2 and the refrigerant fluorocarbon dichlorodifluoromethane. Unlike conventional synthesis, which takes 72 hours using the tetrahydrofuran-water system, this kinetic study showed that Ni-MOF-74 forms within 12 hours under dry-gel conditions with similar performance characteristics, and exhibits its best performance characteristics even after 24 hours of heating. In the dry-gel conversion method, the physical separation of the solvent and precursor mixture allows for recycling of the solvent. We demonstrated efficient solvent recycling (up to three times) that resulted in significant cost benefits. The scaled-up manufacturing cost of Ni-MOF-74 synthesized via our dry-gel method is 45% of conventional synthesis cost. Thus, for bulk production of the MOFs, the proposed vapor-assisted, dry-gel method is efficient, simple, and inexpensive when compared to the conventional synthesis method. PMID:27306598

  13. Synthesis of Hydroxylated Bicyclic Amino Acids from l-Tyrosine: Octahydro-1H-indole Carboxylates

    PubMed Central

    Pierce, Joshua G.; Kasi, Dhanalakshmi; Fushimi, Makoto; Cuzzupe, Anthony; Wipf, Peter

    2009-01-01

    A stereoselective approach to polyhydroxylated l-Choi derivatives has been developed. The oxidative cyclization of l-tyrosine was optimized to avoid partial racemization and to allow a more efficient scale-up. PMID:18767800

  14. Development of efficient, small particle size luminescent oxides using combustion synthesis

    NASA Astrophysics Data System (ADS)

    Shea, Lauren Elizabeth

    Luminescent materials (phosphors) find application in cathode-ray tubes (CRTs), medical and industrial equipment monitors, fluorescent lamps, xerography, and many types of flat panel displays. Many commercially available phosphors were optimized in the 1960s for high voltage (>10 kV) CRT applications. Recently, a great deal of emphasis has been placed on the development and improvement of phosphors for flat panel displays that operate at low voltages (<5 kV). In addition to high efficiency at low voltages, these displays demand high resolution phosphor screens which can only be realized using phosphors with smaller particle size (<3 mum). Conventional methods of preparing phosphors (e.g., high temperature solid-state reaction) cannot easily produce a homogeneous product with uniform, small particle size. In this work, a novel ceramic synthesis technique, combustion synthesis, was used for the first time to produce submicron-sized oxide phosphors more efficiently for use in flat panel displays. This technique exploits the exothermic redox reaction of metal nitrates (oxidizers) with an organic fuel (reducing agent). Typical fuels include urea (CHsb4Nsb2O), carbohydrazide (CHsb6Nsb4O), or glycine (Csb2Hsb5NOsb2). Resulting powders were well-crystallized, with a large surface area and small particle size. Phosphor powders were exposed to photoluminescence excitation by high energy (254 nm, E = 4.88 eV) and low energy photons (365 nm, E = 3.4 eV and 435 nm, E = 2.85 eV) and cathodoluminescence excitation by a low-voltage (100-1000 V) electron beam. Photoluminescence (PL) techniques resulted in the measurement of spectral energy distribution and relative intensities. Phosphor efficiencies in lumens per watt (lm/W) were obtained by low-voltage cathodoluminescence measurements. The effects of processing parameters such as type of fuel, fuel to oxidizer ratio, and heating rate were studied. The combustion process was optimized based on these processing parameters in order

  15. Efficient cascade synthesis of ampicillin from penicillin G potassium salt using wild and mutant penicillin G acylase from Alcaligenes faecalis.

    PubMed

    Deng, Senwen; Ma, Xiaoqiang; Su, Erzheng; Wei, Dongzhi

    2016-02-10

    To avoid isolation and purification of the intermediate 6-aminopenicillanic acid (6-APA), a two-enzyme two-step cascade synthesis of ampicillin from penicillin G was established. In purely aqueous medium, penicillin G hydrolysis and ampicillin synthesis were catalyzed by immobilized wild-type and mutagenized penicillin G acylases from Alcaligenes faecalis (Af PGA), respectively (Fig. 1). The βF24 G mutant Af PGA (the 24th Phenylalanine of the β-subunit was replaced by Glycine) was employed for its superior performance in enzymatic synthesis of ampicillin. By optimizing the reaction conditions, including enzyme loading, temperature, initial pH and D-PGME/6-APA ratio, the conversion of the second step of ampicillin synthesis reached approximately 90% in 240 min and less than 1.7 mole D-PGME were required to produce 1 mole ampicillin. Overall, in a 285 min continuous two-step procedure, an ampicillin yield of 87% was achieved, demonstrating the possibility of improving the cascade synthesis of ampicillin by mutagenized PGA, providing an economically efficient and environmentally benign procedure for semi-synthetic penicillins antibiotics synthesis. PMID:26732414

  16. Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

    PubMed Central

    Bretzke, Sebastian; Scheeff, Stephan; Vollmeyer, Felicitas; Eberhagen, Friederike; Rominger, Frank

    2016-01-01

    Summary The design, development and application of an efficient procedure for the concise synthesis of the 1,3-syn- and anti-tetrahydropyrimidine cores of manzacidins are reported. The intramolecular allylic substitution reaction of a readily available joint urea-type substrate enables the facile preparation of both diastereomers in high yields. The practical application of this approach is demonstrated in the efficient and modular preparation of the authentic heterocyclic cores of manzacidins, structurally unique bromopyrrole alkaloids of marine origin. Additional features of this route include the stereoselective generation of the central amine core with an appending quaternary center by an asymmetric addition of a Grignard reagent to a chiral tert-butanesulfinyl ketimine following an optimized Ellman protocol and a cross-metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid. PMID:27340499

  17. Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji-Trost coupling.

    PubMed

    Bretzke, Sebastian; Scheeff, Stephan; Vollmeyer, Felicitas; Eberhagen, Friederike; Rominger, Frank; Menche, Dirk

    2016-01-01

    The design, development and application of an efficient procedure for the concise synthesis of the 1,3-syn- and anti-tetrahydropyrimidine cores of manzacidins are reported. The intramolecular allylic substitution reaction of a readily available joint urea-type substrate enables the facile preparation of both diastereomers in high yields. The practical application of this approach is demonstrated in the efficient and modular preparation of the authentic heterocyclic cores of manzacidins, structurally unique bromopyrrole alkaloids of marine origin. Additional features of this route include the stereoselective generation of the central amine core with an appending quaternary center by an asymmetric addition of a Grignard reagent to a chiral tert-butanesulfinyl ketimine following an optimized Ellman protocol and a cross-metathesis of a challenging homoallylic urea substrate, which proceeds in good yields in the presence of an organic phosphoric acid. PMID:27340499

  18. Effects of nitric oxide and its synthesis inhibitor on neuron efficiency detected by a fiber-optic-based multisensor

    NASA Astrophysics Data System (ADS)

    Shen, Zheng; Hua, Jun; Lin, Shuzhi; Liu, Xiangfeng

    1998-01-01

    Sodium nitroprusside (SNP) as an exogenous nitric oxide (NO) donor and N(omega) -nitro-L-arginine methyl ester(L-NAME) as NO synthesis inhibitor was driven into monkey cortex by iontophoresis, their effects on face recognition of monkey were observed, and neuron firing as well as neuron efficiency were monitored by fiberoptic-based multisensor during face recognition. The results show that L-NAME and low dose of SNP(5 nM) did not have any significant effect on face recognition and neuron efficiency, however high dose of SNP(50 nM) increased simultaneously both correct rate of face recognition and neuron efficiency, but not neuron firing. The results were discussed according to NO and its synthesis mechanism.

  19. Can oriented-attachment be an efficient growth mechanism for the synthesis of 1D nanocrystals via atomic layer deposition?

    NASA Astrophysics Data System (ADS)

    Wen, Kechun; He, Weidong

    2015-09-01

    One-dimensional (1D) nanocrystals, such as nanorods and nanowires, have received extensive attention in the nanomaterials field due to their large surface areas and 1D confined transport properties. Oriented attachment (OA) is now recognized as a major growth mechanism for efficiently synthesizing 1D nanocrystals. Recently, atomic layer deposition (ALD) has been modified to be a powerful vapor-phase technique with which to synthesize 1D OA nanorods/nanowires with high efficiency and quality by increasing the temperature and purging time. In this invited mini-review, we look into the advantages of OA and high-temperature ALD, and investigate the potential of employing the OA growth mechanism for the synthesis of 1D nanocrystals via modified ALD, aiming to provide guidance to researchers in the fields of both OA and ALD for efficient synthesis of 1D nanocrystals.

  20. Efficient microwave assisted synthesis of metal-organic framework UiO-66: optimization and scale up.

    PubMed

    Taddei, Marco; Dau, Phuong V; Cohen, Seth M; Ranocchiari, Marco; van Bokhoven, Jeroen A; Costantino, Ferdinando; Sabatini, Stefano; Vivani, Riccardo

    2015-08-21

    A highly efficient and scalable microwave assisted synthesis of zirconium-based metal-organic framework UiO-66 was developed. In order to identify the best conditions for optimizing the process, a wide range of parameters was investigated. The efficiency of the process was evaluated with the aid of four quantitative indicators. The properties of the materials prepared by microwave irradiation were compared with those synthesized by conventional heating, and no significant effects on morphology, crystal size, or defects were found from the use of microwave assisted heating. Scale up was performed maintaining the high efficiency of the process. PMID:26165508

  1. Total Synthesis of (-)-Luminacin D.

    PubMed

    Malassis, Julien; Bartlett, Nathan; Hands, Kane; Selby, Matthew D; Linclau, Bruno

    2016-05-01

    A second-generation synthesis of (-)-luminacin D based on an early stage introduction of the trisubstituted epoxide group is reported, allowing access to the natural product in an improved yield and a reduced number of steps (5.4%, 17 steps vs 2.6%, 19 steps). A full account of the optimization work is provided, with the reversal of stereoselection in the formation of the C4 alcohol in equally excellent diastereoselectivity as the key improvement. PMID:27054953

  2. Total synthesis of (-)-uniflorine A.

    PubMed

    Parmeggiani, Camilla; Martella, Daniele; Cardona, Francesca; Goti, Andrea

    2009-11-01

    Total synthesis of (-)-uniflorine A (3) has been accomplished in nine steps and 11% overall yield from carbohydrate-based nitrone 5. The key steps of the synthetic strategy were a high regio- and complete stereoselective 1,3-dipolar cycloaddition of alkene 6 with nitrone 5, a Tamao-Fleming reaction for replacing the silicon substituent with a hydroxy group with retention of configuration, and a Mitsunobu reaction to establish the correct configuration of the target molecule at C-6. PMID:19835391

  3. Total Synthesis and Structural Revision of Antibiotic CJ-16,264**

    PubMed Central

    Nicolaou, K. C.; Shah, Akshay A.; Korman, Henry; Khan, Tabrez; Shi, Lei; Worawalai, Wisuttaya; Theodorakis, Emmanuel A.

    2015-01-01

    The total synthesis and structural revision of antibiotic CJ-16,264 is described. Starting with citronellal, the quest for the target molecule featured a novel bis-transannular Diels–Alder reaction that casted stereoselectively the decalin system and included the synthesis of six isomers before demystification of its true structure. PMID:26096055

  4. Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

    PubMed Central

    Fronert, Jeanne; Bisschops, Tom; Boeck, Florian

    2012-01-01

    Summary The first organocatalytic asymmetric synthesis of smyrindiol, by using an (S)-proline catalyzed enantioselective intramolecular aldol reaction as the key step, is described. Smyrindiol was synthesized from commercially available 2,4-dihydroxybenzaldehyde in 15 steps, with excellent stereoselectivity (de = 99%, ee = 99%). In the course of this total synthesis a new and mild coumarin assembly was developed. PMID:23019438

  5. Simple and efficient synthesis of 2-[(18)F]fluoroethyl triflate for high yield (18)fluoroethylation.

    PubMed

    Peters, Tanja; Vogg, Andreas; Oppel, Iris M; Schmaljohann, Jörn

    2014-12-01

    The [(18)F]fluoroethyl moiety has been widely utilized in the synthesis of (18)F-labelled compounds. The aim of this work was the reliable synthesis of [(18)F]FEtOTf with a novel strategy to increase the reactivity of the commonly used [(18)F]FEB and [(18)F]FEtOTos. [(18)F]FEtOTf and the intermediate [(18)F]FEtOH were synthesized in high RCY (78% and 85%, respectively) and purified by SPE. The high potency of [(18)F]FEtOTf was shown by the efficient alkylation of the deactivated nucleophile aniline under mild conditions, as well as by the synthesis of [(18)F]FEC. PMID:25189703

  6. Novel low temperature synthesis of ZnO nanostructures and its efficient field emission property

    SciTech Connect

    Maiti, U.N.; Ahmed, Sk.F.; Mitra, M.K.; Chattopadhyay, K.K.

    2009-01-08

    We have developed a novel, simple and cost effective wet chemical synthetic route for the production of ZnO nanoneedles and nanoflowers at low temperature. The synthesis process does not require any surfactant, template or pre-seeding. The synthesized ZnO nanoneedles have very sharp tips with their lengths in the range 2-3 {mu}m, while for the case of nanoflowers, the nanoneedles were bunched together. X-ray diffraction study and X-ray photoelectron spectroscopic studies confirmed the formation of pure ZnO phase. Studies on the electron field emission property of the grown nanostructures showed that they are very efficient field emitter. The turn-on fields and the threshold fields are 3.6 V/{mu}m, 4.4 V/{mu}m and 5.4 V/{mu}m, 6.8 V/{mu}m for the ZnO nanoneedles and ZnO nanoflowers, respectively. The enhanced field emission property was attributed to the presence of sharp tips of the nanostructures.

  7. Phase and composition controllable synthesis of cobalt manganese spinel nanoparticles towards efficient oxygen electrocatalysis

    NASA Astrophysics Data System (ADS)

    Li, Chun; Han, Xiaopeng; Cheng, Fangyi; Hu, Yuxiang; Chen, Chengcheng; Chen, Jun

    2015-06-01

    Spinel-type oxides are technologically important in many fields, including electronics, magnetism, catalysis and electrochemical energy storage and conversion. Typically, these materials are prepared by conventional ceramic routes that are energy consuming and offer limited control over shape and size. Moreover, for mixed-metal oxide spinels (for example, CoxMn3-xO4), the crystallographic phase sensitively correlates with the metal ratio, posing great challenges to synthesize active product with simultaneously tuned phase and composition. Here we report a general synthesis of ultrasmall cobalt manganese spinels with tailored structural symmetry and composition through facile solution-based oxidation-precipitation and insertion-crystallization process at modest condition. As an example application, the nanocrystalline spinels catalyse the oxygen reduction/evolution reactions, showing phase and composition co-dependent performance. Furthermore, the mild synthetic strategy allows the formation of homogeneous and strongly coupled spinel/carbon nanocomposites, which exhibit comparable activity but superior durability to Pt/C and serve as efficient catalysts to build rechargeable Zn-air and Li-air batteries.

  8. Facile Synthesis of Graphene Sponge from Graphene Oxide for Efficient Dye-Sensitized H2 Evolution.

    PubMed

    Zhang, Weiying; Li, Yuexiang; Peng, Shaoqin

    2016-06-22

    Graphene is an advanced carbon energy material due to its excellent properties. Reduction of graphene oxide (GO) is the most promising mass production route of graphene/reduced graphene oxide (rGO). To maintain graphene's properties and avoid restacking of rGO sheets in bulk, the preparation of 3-dimensional porous graphene sponge via 2-dimensional rGO sheets is considered as a good strategy. This article presents a facile route to synthesize graphene sponge by thermal treating GO powder at low temperature of 250 °C under N2 atmosphere. The sponge possesses macroporous structure (5-200 nm in size) with BET specific surface area of 404 m(2) g(-1) and high conductivity. The photocatalytic H2 production activity of the rGO sponge with a sensitizer Eosin Y (EY) and cocatalyst Pt was investigated. The rGO sponge shows highly efficient dye-sensitized photocatalytic H2 evolution compared to that obtained via a chemical reduction method. The maximum apparent quantum yield (AQY) reaches up to 75.0% at 420 nm. The possible mechanisms are discussed. The synthesis method can be expanded to prepare other graphene-based materials. PMID:27244655

  9. Efficient synthesis of tension modulation in strings and membranes based on energy estimation.

    PubMed

    Avanzini, Federico; Marogna, Riccardo; Bank, Balázs

    2012-01-01

    String and membrane vibrations cannot be considered as linear above a certain amplitude due to the variation in string or membrane tension. A relevant special case is when the tension is spatially constant and varies in time only in dependence of the overall string length or membrane surface. The most apparent perceptual effect of this tension modulation phenomenon is the exponential decay of pitch in time. Pitch glides due to tension modulation are an important timbral characteristic of several musical instruments, including the electric guitar and tom-tom drum, and many ethnic instruments. This paper presents a unified formulation to the tension modulation problem for one-dimensional (1-D) (string) and two-dimensional (2-D) (membrane) cases. In addition, it shows that the short-time average of the tension variation, which is responsible for pitch glides, is approximately proportional to the system energy. This proportionality allows the efficient physics-based sound synthesis of pitch glides. The proposed models require only slightly more computational resources than linear models as opposed to earlier tension-modulated models of higher complexity. PMID:22280712

  10. Phase and composition controllable synthesis of cobalt manganese spinel nanoparticles towards efficient oxygen electrocatalysis

    PubMed Central

    Li, Chun; Han, Xiaopeng; Cheng, Fangyi; Hu, Yuxiang; Chen, Chengcheng; Chen, Jun

    2015-01-01

    Spinel-type oxides are technologically important in many fields, including electronics, magnetism, catalysis and electrochemical energy storage and conversion. Typically, these materials are prepared by conventional ceramic routes that are energy consuming and offer limited control over shape and size. Moreover, for mixed-metal oxide spinels (for example, CoxMn3−xO4), the crystallographic phase sensitively correlates with the metal ratio, posing great challenges to synthesize active product with simultaneously tuned phase and composition. Here we report a general synthesis of ultrasmall cobalt manganese spinels with tailored structural symmetry and composition through facile solution-based oxidation–precipitation and insertion–crystallization process at modest condition. As an example application, the nanocrystalline spinels catalyse the oxygen reduction/evolution reactions, showing phase and composition co-dependent performance. Furthermore, the mild synthetic strategy allows the formation of homogeneous and strongly coupled spinel/carbon nanocomposites, which exhibit comparable activity but superior durability to Pt/C and serve as efficient catalysts to build rechargeable Zn–air and Li–air batteries. PMID:26040417

  11. An efficient solid-phase synthesis of peptidyl-N-acetylguanidines for use in native chemical ligation.

    PubMed

    Okamoto, Ryo; Isoe, Madoka; Izumi, Masayuki; Kajihara, Yasuhiro

    2016-05-01

    In the modern protocols of chemical protein syntheses, peptide-α-thioesters have been used as key components for the assembly of full-length polypeptides through chemoselective peptide coupling reactions. A variety of thioester precursors have been developed for the synthesis of the peptide-α-thioesters by Fmoc solid phase peptide synthesis (Fmoc-SPPS). Recently our group found a peptidyl-N-acetylguanidine as a new peptide-α-thioester precursor. This peptide derivative can be converted into a corresponding peptide-α-thioester only by treatment with an excess amount of a thiol in aqueous buffers at around neutral pH. This unique property allowed us to envision the practical use of the peptidyl-N-acetylguanidines for the chemical syntheses of proteins; however, an efficient synthetic method has been lacking. Herein, we report an efficient solid-phase synthesis of peptidyl-N-acetylguanidines. This new synthetic method employing selective activation and cleavage of a peptide bond successfully provided peptidyl-N-acetylguanidines from the on-resin protected peptides prepared by standard Fmoc-SPPS. We also evaluated the reactivity of a peptidyl-N-acetylguanidine in native chemical ligation through the synthesis of glucose-dependent insulinotropic polypeptide analogue. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27005965

  12. An Efficient Solution-Phase Synthesis of 4,5,7-Trisubstituted Pyrrolo[3,2-d]pyrimidines

    PubMed Central

    Zhang, Weihe; Liu, Jing; Stashko, Michael A.; Wang, Xiaodong

    2013-01-01

    We have developed an efficient and robust route to synthesize 4,5,7-trisubstituted pyrrolo[3,2-d]pyrimidines as potent kinase inhibitors. This solution-phase synthesis features a SNAr substitution reaction, cross-coupling reaction, one-pot reduction/reductive amination and N-alkylation reaction. These reactions occur rapidly with high yields and have broad substrate scopes. A variety of groups can be selectively introduced into the N5 and C7 positions of 4,5,7-trisubstituted pyrrolopyrimidines at a late stage of the synthesis, thereby providing a highly efficient approach to explore the structure-activity relationships of pyrrolopyrimidine derivatives. Four synthetic analogs have been profiled against a panel of 48 kinases and a new and selective FLT3 inhibitor 9 is identified. PMID:23181516

  13. Efficient Organocatalytic Construction of C4-Alkyl Substituted Piperidines and Their Application to the Synthesis of (+)-α-Skytanthine.

    PubMed

    Shiomi, Shinya; Sugahara, Erika; Ishikawa, Hayato

    2015-10-12

    Chiral piperidines which contain an alkyl group at C4 positions are one of the important architectures because it is appeared in several natural products. An efficient protocol for the preparation of C4-alkyl substituted chiral piperidines using secondary amine catalyzed formal aza [3+3] cycloaddition reaction with aliphatic α,β-unsaturated aldehydes and thiomalonamate derivatives is reported. In our reaction system, thiomalonamate is an excellent nucleophile and the addition of suitable acid and its amount is an important factor for the acceleration effect in organocatalytic reaction. Furthermore, water and MeOH also have an acceleration effect. These efforts lead to only 0.1 mol % catalyst loading in multigram scale synthesis for suitable reaction time. In addition, the efficient enantioselective total synthesis of (+)-α-skytanthine by using our developed reaction as key step was achieved in total 15 % yield. All carbon and nitrogen units were introduced by one step with high enantioselectivity. PMID:26333476

  14. Time- and energy-efficient solution combustion synthesis of binary metal tungstate nanoparticles with enhanced photocatalytic activity.

    PubMed

    Thomas, Abegayl; Janáky, Csaba; Samu, Gergely F; Huda, Muhammad N; Sarker, Pranab; Liu, J Ping; van Nguyen, Vuong; Wang, Evelyn H; Schug, Kevin A; Rajeshwar, Krishnan

    2015-05-22

    In the search for stable and efficient photocatalysts beyond TiO2 , the tungsten-based oxide semiconductors silver tungstate (Ag2 WO4 ), copper tungstate (CuWO4 ), and zinc tungstate (ZnWO4 ) were prepared using solution combustion synthesis (SCS). The tungsten precursor's influence on the product was of particular relevance to this study, and the most significant effects are highlighted. Each sample's photocatalytic activity towards methyl orange degradation was studied and benchmarked against their respective commercial oxide sample obtained by solid-state ceramic synthesis. Based on the results herein, we conclude that SCS is a time- and energy-efficient method to synthesize crystalline binary tungstate nanomaterials even without additional excessive heat treatment. As many of these photocatalysts possess excellent photocatalytic activity, the discussed synthetic strategy may open sustainable materials chemistry avenues to solar energy conversion and environmental remediation. PMID:26018624

  15. Substrate-Controlled Asymmetric Total Synthesis and Structure Revision of (-)-Bisezakyne A.

    PubMed

    Shin, Iljin; Lee, Dongjoo; Kim, Hyoungsu

    2016-09-01

    The first asymmetric total synthesis and subsequent structure revision of (-)-bisezakyne A, a Laurencia C15 acetogenin from Alpysia oculifera, has been accomplished. Our substrate-controlled synthesis of this oxolane natural product features a highly stereoselective "protecting-group-dependent" intramolecular amide enolate alkylation strategy for the synthesis of the key 9,10-trans-9,12-cis-10-hydroxytetrahydrofuran intermediate through "nonchelate" control. In addition, our synthesis determined the absolute configuration of the halogenated marine natural product. PMID:27551943

  16. A Simple, Efficient Synthesis of 2-Aryl Benzimidazoles Using Silica Supported Periodic Acid Catalyst and Evaluation of Anticancer Activity

    PubMed Central

    Sontakke, Vyankat A.; Ghosh, Sougata; Lawande, Pravin P.; Chopade, Balu A.; Shinde, Vaishali S.

    2013-01-01

    A new, efficient method for the synthesis of 2-aryl substituted benzimidazole by using silica supported periodic acid (H5IO6-SiO2) as a catalyst has been developed. The salient feature of the present method includes mild reaction condition, short reaction time, high yield and easy workup procedure. The synthesized benzimidazoles exhibited potent anticancer activity against MCF7 and HL60 cell lines. PMID:24052861

  17. Tuning the basicity of ionic liquids for efficient synthesis of alkylidene carbonates from CO2 at atmospheric pressure.

    PubMed

    Chen, Kaihong; Shi, Guiling; Dao, Rina; Mei, Ke; Zhou, Xiuyuan; Li, Haoran; Wang, Congmin

    2016-06-14

    A strategy to achieve the efficient synthesis of alkylidene carbonates from CO2 at atmospheric pressure by tuning the basicity of ionic liquids was developed. Excellent yields were obtained due to basic ionic liquids' dual roles both as absorbents and as activators. The reaction mechanism was investigated through a combination of NMR spectroscopy, controlled experiments and quantum calculations, indicating the importance of a moderate basicity. PMID:27241057

  18. Synthesis of substituted 1,4-diazepines and 1,5-benzodiazepines using an efficient heteropolyacid-catalyzed procedure.

    PubMed

    Kaoua, Rachedine; Bennamane, Norah; Bakhta, Saliha; Benadji, Sihame; Rabia, Cherifa; Nedjar-Kolli, Bellara

    2011-01-01

    An efficient and improved procedure for the synthesis of 1,4-diazepine and 1,5-benzodiazepine derivatives via the reaction of ketimine intermediates with aldehydes in the presence of Keggin-type heteropolyacids (HPAs) was developed. High yields and short reaction times were obtained for both electron-releasing and electron-withdrawing substituted 1,4-diazepine  and 1,5-benzodiazepines derivatives. PMID:21189457

  19. One-pot hydrazide-based native chemical ligation for efficient chemical synthesis and structure determination of toxin Mambalgin-1.

    PubMed

    Pan, Man; He, Yao; Wen, Ming; Wu, Fangming; Sun, Demeng; Li, Sijian; Zhang, Longhua; Li, Yiming; Tian, Changlin

    2014-06-01

    An efficient one-pot chemical synthesis of snake venom toxin Mambalgin-1 was achieved using an azide-switch strategy combined with hydrazide-based native chemical ligation. Synthetic Mambalgin-1 exhibited a well-defined structure after sequential folding in vitro. NMR spectroscopy revealed a three-finger toxin family structure, and the synthetic toxin inhibited human acid-sensing ion channel 1a. PMID:24619065

  20. Efficient continuous synthesis of high purity deep eutectic solvents by twin screw extrusion.

    PubMed

    Crawford, D E; Wright, L A; James, S L; Abbott, A P

    2016-03-18

    Mechanochemical synthesis has been applied to the rapid synthesis of Deep Eutectic Solvents (DESs), including Reline 200 (choline chloride : urea, 1 : 2), in a continuous flow methodology by Twin Screw Extrusion (TSE). This gave products in higher purity and with Space Time Yields (STYs), four orders of magnitude greater than for batch methods. PMID:26911554

  1. HELP (high efficiency liquid phase) new oligonucleotide synthesis on soluble polymeric support.

    PubMed

    Bonora, G M; Scremin, C L; Colonna, F P; Garbesi, A

    1990-06-11

    A simple, rapid and high-yielding method for the synthesis of oligonucleotides by the phosphotriesters approach is described. The use of polyethylene glycol (PEG) as soluble polymeric support preserves some convenient features of the solid-phase synthesis with new interesting advantages. Short oligonucleotides in hundred milligrams scale can be obtained from few grams of functionalized PEG. PMID:2356115

  2. HELP (high efficiency liquid phase) new oligonucleotide synthesis on soluble polymeric support.

    PubMed Central

    Bonora, G M; Scremin, C L; Colonna, F P; Garbesi, A

    1990-01-01

    A simple, rapid and high-yielding method for the synthesis of oligonucleotides by the phosphotriesters approach is described. The use of polyethylene glycol (PEG) as soluble polymeric support preserves some convenient features of the solid-phase synthesis with new interesting advantages. Short oligonucleotides in hundred milligrams scale can be obtained from few grams of functionalized PEG. PMID:2356115

  3. Stereoselective Reduction of Prochiral Ketones by Plant and Microbial Biocatalysts.

    PubMed

    Javidnia, K; Faghih-Mirzaei, E; Miri, R; Attarroshan, M; Zomorodian, K

    2016-01-01

    Chiral alcohols are the key chiral building blocks to many enantiomerically pure pharmaceuticals. The biocatalytic approach in asymmetric reduction of corresponding prochiral ketones to the preparation of these optically pure substances is one of the most promising routes. The stereoselective reduction of different kinds of prochiral ketones catalyzed by various plants and microorganisms was studied in this work. Benzyl acetoacetate, methyl 3-oxopentanoate, ethyl 3-oxopentanoate, and ethyl butyryl acetate were chosen as the model substrates for β-ketoesters. Benzoyl acetonitrile, 3-chloro propiophenone, and 1-acetyl naphthalene were chosen as aromatic aliphatic ketones. Finally, 2-methyl benzophenone and 4-chloro benzophenone were selected as diaryl ketones. Plant catalysis was conducted by Daucus carota, Brassica rapa, Brassica oleracea, Pastinaca sativa, and Raphnus sativus. For microbial catalysis, Aspergillus foetidus, Penicillum citrinum, Saccharomyces carlbergensis, Pichia fermentans, and Rhodotrula glutinis were chosen. Chiral alcohols were obtained in high yields and with optical purity. A superiority in the microorganisms' performance in the bioreduction of prochiral ketones was detected. Among microorganisms, Rhodotrula glutinis showed remarkable results with nearly all substrates and is proposed for future studies. PMID:27168684

  4. Stereoselective Reduction of Prochiral Ketones by Plant and Microbial Biocatalysts

    PubMed Central

    Javidnia, K.; Faghih-Mirzaei, E.; Miri, R.; Attarroshan, M.; Zomorodian, K.

    2016-01-01

    Chiral alcohols are the key chiral building blocks to many enantiomerically pure pharmaceuticals. The biocatalytic approach in asymmetric reduction of corresponding prochiral ketones to the preparation of these optically pure substances is one of the most promising routes. The stereoselective reduction of different kinds of prochiral ketones catalyzed by various plants and microorganisms was studied in this work. Benzyl acetoacetate, methyl 3-oxopentanoate, ethyl 3-oxopentanoate, and ethyl butyryl acetate were chosen as the model substrates for β-ketoesters. Benzoyl acetonitrile, 3-chloro propiophenone, and 1-acetyl naphthalene were chosen as aromatic aliphatic ketones. Finally, 2-methyl benzophenone and 4-chloro benzophenone were selected as diaryl ketones. Plant catalysis was conducted by Daucus carota, Brassica rapa, Brassica oleracea, Pastinaca sativa, and Raphnus sativus. For microbial catalysis, Aspergillus foetidus, Penicillum citrinum, Saccharomyces carlbergensis, Pichia fermentans, and Rhodotrula glutinis were chosen. Chiral alcohols were obtained in high yields and with optical purity. A superiority in the microorganisms' performance in the bioreduction of prochiral ketones was detected. Among microorganisms, Rhodotrula glutinis showed remarkable results with nearly all substrates and is proposed for future studies. PMID:27168684

  5. Synthesis of an Aminooxy Derivative of the Tetrasaccharide Repeating Unit of Streptococcus dysgalactiae 2023 Polysaccharide for a PS A1 Conjugate Vaccine.

    PubMed

    Ghosh, Samir; Nishat, Sharmeen; Andreana, Peter R

    2016-06-01

    A highly efficient and stereocontrolled synthesis of an aminooxy derivative of the tetrasaccharide repeating unit of a rhamnose-rich polysaccharide isolated from the cell envelop of bovine mastitis Streptococcus dysgalactiae 2023 is reported for the first time. The synthesis was accomplished utilizing a stereoselective and convergent [2 + 2] glycosylation strategy inclusive of a disaccharide Schmidt donor and an inclusive rhamnose disaccharide acceptor. The synthetic aminooxy tetrasaccharide was conjugated to T-cell stimulating immunogen PS A1 from Bacteroides fragilis ATCC 25285/NCTC 9343 via a physiologically stable oxime linkage to furnish the first semisynthetic bacterial-based immunogen construct targeting S. dysgalactiae 2023. The synthetic tetrasaccharide was assembled in 19 steps with a ∼5.0% overall yield. PMID:27149417

  6. Efficient Synthesis of Highly Luminescent Copper Indium Sulfide-Based Core/Shell Nanocrystals with Surprisingly Long-Lived Emission

    SciTech Connect

    Li, Liang; Pandey, Anshu; Werder, Donald J.; Khanal, Bishnu P.; Pietryga, Jeffrey M.; Klimov, Victor I.

    2011-02-09

    We report an efficient synthesis of copper indium sulfide nanocrystals with strong photoluminescence in the visible to near-infrared. This method can produce gram quantities of material with a chemical yield in excess of 90% with minimal solvent waste. The overgrowth of as-prepared nanocrystals with a few monolayers of CdS or ZnS increases the photoluminescence quantum efficiency to > 80%. On the basis of time-resolved spectroscopic studies of core/shell particles, we conclude that the emission is due to an optical transition that couples a quantized electron state to a localized hole state, which is most likely associated with an internal defect.

  7. Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis

    PubMed Central

    Hack, Daniel; Dürr, Alexander B; Deckers, Kristina; Chauhan, Pankaj; Seling, Nico; Rübenach, Lukas; Mertens, Lucas; Raabe, Gerhard; Schoenebeck, Franziska; Enders, Dieter

    2016-01-01

    A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments. PMID:26676875

  8. Asymmetric Synthesis of Spiropyrazolones by Sequential Organo- and Silver Catalysis.

    PubMed

    Hack, Daniel; Dürr, Alexander B; Deckers, Kristina; Chauhan, Pankaj; Seling, Nico; Rübenach, Lukas; Mertens, Lucas; Raabe, Gerhard; Schoenebeck, Franziska; Enders, Dieter

    2016-01-26

    A stereoselective one-pot synthesis of spiropyrazolones through an organocatalytic asymmetric Michael addition and a formal Conia-ene reaction has been developed. Depending on the nitroalkene, the 5-exo-dig-cyclization could be achieved by silver-catalyzed alkyne activation or by oxidation of the intermediate enolate. The mechanistic pathways have been investigated using computational chemistry and mechanistic experiments. PMID:26676875

  9. Direct formation of small Cu2O nanocubes, octahedra, and octapods for efficient synthesis of triazoles

    NASA Astrophysics Data System (ADS)

    Tsai, Ya-Huei; Chanda, Kaushik; Chu, Yi-Ting; Chiu, Chun-Ya; Huang, Michael H.

    2014-07-01

    In most studies describing the preparation of Cu2O crystals of various morphologies, the particle sizes are normally hundreds of nanometers to micrometers due to rapid particle growth, so they are not exactly nanocrystals. Here we report surfactant-free formation of sub-100 nm Cu2O nanocrystals with systematic shape evolution from cubic to octahedral structures by preparing an aqueous mixture of Cu(OAc)2, NaOH, and N2H4 solution. Adjustment of the hydrazine volume enables the particle shape control. Uniform nanocubes and octahedra were synthesized with edge lengths of 37 and 67 nm, respectively. Novel Cu2O octapods with an edge length of 135 nm were also produced by mixing CuCl2 solution, SDS surfactant, NaOH solution, and NH2OH.HCl reductant solution. All of them are nearly the smallest Cu2O nanocrystals of the same shapes ever reported. These small cubes, octahedra, and octapods were employed as catalysts in the direct synthesis of 1,2,3-triazoles from the reaction of alkynes, organic halides, and NaN3 at 55 °C. All of them displayed high product yields in short reaction times. The octahedra enclosed by the {111} facets are the best catalysts, and can catalyze this cycloaddition reaction with high yields in just 2 h when different alkynes were used to make diverse triazole products. Hence, the small Cu2O particles provide time-saving, energy-efficient, and high product yield benefits to organocatalysis.In most studies describing the preparation of Cu2O crystals of various morphologies, the particle sizes are normally hundreds of nanometers to micrometers due to rapid particle growth, so they are not exactly nanocrystals. Here we report surfactant-free formation of sub-100 nm Cu2O nanocrystals with systematic shape evolution from cubic to octahedral structures by preparing an aqueous mixture of Cu(OAc)2, NaOH, and N2H4 solution. Adjustment of the hydrazine volume enables the particle shape control. Uniform nanocubes and octahedra were synthesized with edge

  10. Synthesis of Colloidal Nanocrystal Heterostructures for High-Efficiency Light Emission

    NASA Astrophysics Data System (ADS)

    Lu, Yifei

    Group II-VI semiconductor nanocrystals, particularly those based on ZnCdS(Se), can be synthesized using well established chemical colloidal processes, and have been a subject of extensive research over the past decade. Their optical properties can be easily tuned through size and composition variations, making them very attractive for many optoelectronic applications including light-emitting diodes (LEDs) and solar cells. Incorporation of diverse internal heterostructures provides an additional means for tuning the optical and electronic properties of conventional ZnCdS(Se) nanocrystals. Extensive bandgap and strain engineering may be applied to the resultant nanocrystal heterostructures to achieve desirable properties and enhanced performance. Despite the high scientific and practical interests of this unique class of nanomaterials, limited efforts have been made to explore their synthesis and potential device applications. This thesis focuses on the synthesis, engineering, characterization, and device demonstration of two types of CdSe-based nanocrystal heterostructures: core/multishell quantum dots (QDs) and QD quantum wells (QDQWs). Their optical properties have been tuned by bandgap and strain engineering to achieve efficient photoluminescence (PL) and electroluminescence (EL).Firstly, yellow light-emitting CdSe QDs with a strain-compensated ZnS/ZnCdS bilayer shell were synthesized using the successive ion layer adsorption and reaction technique and the effects of the shell on the luminescent properties were investigated. The core/shell/shell QDs enjoyed the benefits of excellent exciton confinement by the ZnS intermediate shell and strain compensation by the ZnCdS outer shell, and exhibited 40% stronger PL and a smaller peak redshift upon shell growth compared to conventional CdSe/ZnCdS/ZnS core/shell/shell QDs with an intermediate lattice adaptor. CdSe/ZnS/ZnCdS QD-LEDs had a luminance of 558 cd/m2 at 20 mA/cm 2, 28% higher than that of CdSe/ZnCdS/ZnS QD

  11. Sequence and structure-specific elements of HERG mRNA determine channel synthesis and trafficking efficiency

    PubMed Central

    Sroubek, Jakub; Krishnan, Yamini; McDonald, Thomas V.

    2013-01-01

    Human ether-á-gogo-related gene (HERG) encodes a potassium channel that is highly susceptible to deleterious mutations resulting in susceptibility to fatal cardiac arrhythmias. Most mutations adversely affect HERG channel assembly and trafficking. Why the channel is so vulnerable to missense mutations is not well understood. Since nothing is known of how mRNA structural elements factor in channel processing, we synthesized a codon-modified HERG cDNA (HERG-CM) where the codons were synonymously changed to reduce GC content, secondary structure, and rare codon usage. HERG-CM produced typical IKr-like currents; however, channel synthesis and processing were markedly different. Translation efficiency was reduced for HERG-CM, as determined by heterologous expression, in vitro translation, and polysomal profiling. Trafficking efficiency to the cell surface was greatly enhanced, as assayed by immunofluorescence, subcellular fractionation, and surface labeling. Chimeras of HERG-NT/CM indicated that trafficking efficiency was largely dependent on 5′ sequences, while translation efficiency involved multiple areas. These results suggest that HERG translation and trafficking rates are independently governed by noncoding information in various regions of the mRNA molecule. Noncoding information embedded within the mRNA may play a role in the pathogenesis of hereditary arrhythmia syndromes and could provide an avenue for targeted therapeutics.—Sroubek, J., Krishnan, Y., McDonald, T V. Sequence- and structure-specific elements of HERG mRNA determine channel synthesis and trafficking efficiency. PMID:23608144

  12. Total synthesis of atropurpuran.

    PubMed

    Gong, Jing; Chen, Huan; Liu, Xiao-Yu; Wang, Zhi-Xiu; Nie, Wei; Qin, Yong

    2016-01-01

    Due to their architectural intricacy and biological significance, the synthesis of polycyclic diterpenes and their biogenetically related alkaloids have been the subject of considerable interest over the last few decades, with progress including the impressive synthesis of several elusive targets. Despite tremendous efforts, conquering the unique structural types of this large natural product family remains a long-term challenge. The arcutane diterpenes and related alkaloids, bearing a congested tetracyclo[5.3.3.0(4,9).0(4,12)]tridecane unit, are included in these unsolved enigmas. Here we report a concise approach to the construction of the core structure of these molecules and the first total synthesis of (±)-atropurpuran. Pivotal features of the synthesis include an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, sequential aldol and ketyl-olefin cyclizations to assemble the highly caged framework, and a chemoselective and stereoselective reduction to install the requisite allylic hydroxyl group in the target molecule. PMID:27387707

  13. Total synthesis of atropurpuran

    PubMed Central

    Gong, Jing; Chen, Huan; Liu, Xiao-Yu; Wang, Zhi-Xiu; Nie, Wei; Qin, Yong

    2016-01-01

    Due to their architectural intricacy and biological significance, the synthesis of polycyclic diterpenes and their biogenetically related alkaloids have been the subject of considerable interest over the last few decades, with progress including the impressive synthesis of several elusive targets. Despite tremendous efforts, conquering the unique structural types of this large natural product family remains a long-term challenge. The arcutane diterpenes and related alkaloids, bearing a congested tetracyclo[5.3.3.04,9.04,12]tridecane unit, are included in these unsolved enigmas. Here we report a concise approach to the construction of the core structure of these molecules and the first total synthesis of (±)-atropurpuran. Pivotal features of the synthesis include an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, sequential aldol and ketyl-olefin cyclizations to assemble the highly caged framework, and a chemoselective and stereoselective reduction to install the requisite allylic hydroxyl group in the target molecule. PMID:27387707

  14. Characterization of a Zinc-Containing Alcohol Dehydrogenase with Stereoselectivity from the Hyperthermophilic Archaeon Thermococcus guaymasensis▿

    PubMed Central

    Ying, Xiangxian; Ma, Kesen

    2011-01-01

    An alcohol dehydrogenase (ADH) from hyperthermophilic archaeon Thermococcus guaymasensis was purified to homogeneity and was found to be a homotetramer with a subunit size of 40 ± 1 kDa. The gene encoding the enzyme was cloned and sequenced; this gene had 1,095 bp, corresponding to 365 amino acids, and showed high sequence homology to zinc-containing ADHs and l-threonine dehydrogenases with binding motifs of catalytic zinc and NADP+. Metal analyses revealed that this NADP+-dependent enzyme contained 0.9 ± 0.03 g-atoms of zinc per subunit. It was a primary-secondary ADH and exhibited a substrate preference for secondary alcohols and corresponding ketones. Particularly, the enzyme with unusual stereoselectivity catalyzed an anti-Prelog reduction of racemic (R/S)-acetoin to (2R,3R)-2,3-butanediol and meso-2,3-butanediol. The optimal pH values for the oxidation and formation of alcohols were 10.5 and 7.5, respectively. Besides being hyperthermostable, the enzyme activity increased as the temperature was elevated up to 95°C. The enzyme was active in the presence of methanol up to 40% (vol/vol) in the assay mixture. The reduction of ketones underwent high efficiency by coupling with excess isopropanol to regenerate NADPH. The kinetic parameters of the enzyme showed that the apparent Km values and catalytic efficiency for NADPH were 40 times lower and 5 times higher than those for NADP+, respectively. The physiological roles of the enzyme were proposed to be in the formation of alcohols such as ethanol or acetoin concomitant to the NADPH oxidation. PMID:21515780

  15. An efficient and mild oxidant for the synthesis of s-tetrazines

    PubMed Central

    Selvaraj, Ramajeyam; Fox, Joseph M.

    2014-01-01

    PhI(OAc)2 serves as a mild and effective oxidant for the synthesis of s-tetrazine derivatives— molecules of emerging significance to the field of bioorthogonal chemistry. This reagent serves as a complementary oxidant to harsher nitrous reagents. Use of PhI(OAc)2 improves the synthesis of 5-amino-di(pyridin-2-yl)-s-tetrazine, a molecule that has been broadly used for cellular imaging and nuclear medicine. The generality of PhI(OAc)2 as the oxidant for tetrazine synthesis is demonstrated for nine tetrazines in 75–98% yield. PMID:26146418

  16. One-Pot Catalysis Using a Chiral Iridium Complex/Brønsted Base: Catalytic Asymmetric Synthesis of Catalponol.

    PubMed

    Suzuki, Takeyuki; Ismiyarto; Ishizaka, Yuka; Zhou, Da-Yang; Asano, Kaori; Sasai, Hiroaki

    2015-11-01

    Tandem asymmetric hydrogen transfer oxidation/aldol condensation under relay catalysis of a chiral iridium complex/achiral Brønsted base binary system is described for the synthesis of α-benzylidene-γ-hydroxytetralones with high ee's. A two-step synthesis of catalponol was achieved using this sequential methodology together with regio- and stereoselective hydroboration. PMID:26496409

  17. I. Development of Metal-Mediated SPOT-Synthesis Methods for the Efficient Construction of Small-Molecule Macroarrays. II. Design and Synthesis of Novel Bacterial Biofilm Inhibitors

    NASA Astrophysics Data System (ADS)

    Frei, Reto

    I. The use of small molecule probes to explore biological phenomena has become a valuable tool in chemical biology. As a result, methods that permit the rapid synthesis and biological evaluation of such compounds are highly sought-after. The small molecule macroarray represents one such approach for the synthesis and identification of novel bioactive agents. Macroarrays are readily constructed via the SPOT-synthesis technique on planar cellulose membranes, yielding spatially addressed libraries of ˜10-1000 unique compounds. We sought to expand the arsenal of chemical reactions compatible with this solid-phase platform, and developed highly efficient SPOT-synthesis protocols for the Mizoroki-Heck, Suzuki-Miyaura, and copper-catalyzed azide-alkyne cycloaddition reaction. We demonstrated that these metal-mediated reactions can be implemented, either individually or sequentially, for the efficient construction of small molecules in high purity on rapid time scales. Utilizing these powerful C-C and C-N bond forming coupling reactions, we constructed a series of macroarrays based on novel stilbene, phenyl-naphthalene, and triazole scaliblds. Subsequent biological testing of the stilbene and phenyl-naphthalene libraries revealed several potent antagonists and agonists, respectively, of the quorum sensing (QS) receptor LuxR in Vibrio fischeri. II. Bacteria living within biofilms are notorious for their resistance to known antibiotic agents, and constitute a major human health threat. Methods to attenuate biofilm growth would have a significant impact on the management of bacterial infections. Despite intense research efforts, small molecules capable of either inhibiting or dispersing biolilms remain scarce. We utilized natural products with purported anti-biofilm or QS inhibitory activity as sources of structural insight to guide the synthesis of novel biofilm modulators with improved activities. These studies revealed 2-aminobenzimidazole derivatives as highly potent

  18. Conformations of allylic fluorides and stereoselectivities of their diels-alder cycloadditions.

    PubMed

    Grée, D; Vallerie, L; Grée, R; Toupet, L; Washington, I; Pelicier, J P; Villacampa, M; Pérez, J M; Houk, K N

    2001-04-01

    The preparations of new allylic fluorides from the corresponding alcohols are reported. Conformational analysis is achieved by comparison of experimental NMR measurements with theoretical (B3LYP) calculations of relative energies of conformers and J(H,H) and J(H,F) coupling constants. The Diels-Alder reactions of allylic fluorides are investigated experimentally and theoretically. The stereoselectivities of the reactions were determined by NMR analysis and, in one case, by X-ray crystallography. Theoretical predictions of stereoselectivity based upon transition state modeling provided good agreement with experiment. Theoretical models for allylic fluorides and transition state conformations are reported. PMID:11281778

  19. Chemoselective and stereoselective lithium carbenoid mediated cyclopropanation of acyclic allylic alcohols.

    PubMed

    Durán-Peña, M J; Flores-Giubi, M E; Botubol-Ares, J M; Harwood, L M; Collado, I G; Macías-Sánchez, A J; Hernández-Galán, R

    2016-03-01

    The reaction of geraniol with different lithium carbenoids generated from n-BuLi and the corresponding dihaloalkane has been evaluated. The reaction occurs in a chemo and stereoselective manner, which is consistent with a directing effect from the oxygen of the allylic moiety. Furthermore, a set of polyenes containing allylic hydroxyl or ether groups were chemoselectively and stereoselectively converted into the corresponding gem-dimethylcyclopropanes in one single step in moderate to good yields mediated by a lithium carbenoid generated in situ by the reaction of n-BuLi and 2,2-dibromopropane. PMID:26846582

  20. Evolving P450pyr Monooxygenase for Regio- and Stereoselective Hydroxylations.

    PubMed

    Yang, Yi; Li, Zhi

    2015-01-01

    P450pyr monooxygenase from Sphingomonas sp. HXN-200 catalysed the regio- and stereoselective hydroxylation at a non-activated carbon atom, a useful but challenging reaction in classic chemistry, with unique substrate specificity for a number of alicyclic compounds. New P450pyr mutants were developed by directed evolution with improved catalytic performance, thus significantly extending the application of the P450pyr monooxygenase family in biohydroxylation to prepare useful and valuable chiral alcohols. Directed evolution of P450pyr created new enzymes with improved S-enantioselectivity or R-enantioselectivity for the hydroxylation of N-benzyl pyrrolidine, enhanced regioselectivity for the hydroxylation of N-benzyl pyrrolidinone, and increased enantioselectivity for the hydroxylation of N-benzyl piperidinone, respectively. Directed evolution of P450pyr generated also mutants with fully altered regioselectivity (from terminal to subterminal) and newly created excellent S-enantioselectivity for the biohydroxylation of n-octane and propylbenzene, respectively, providing new opportunities for the regio- and enantioselective alkane functionalization. New P450pyr mutants were engineered as the first catalyst for highly selective terminal hydroxylation of n-butanol to 1,4-butanediol. Several novel, accurate, sensitive, simple, and HTS assays based on colorimetric or MS detection for measuring the enantio- and/or regioselectivity of hydroxylation were developed and proven to be practical in directed evolution. The P450pyr X-ray structure was obtained and used to guide the evolution. In silico modelling and substrate docking provided some insight into the influence of several important amino acid mutations of the engineered P450pyr mutants on the altered or enhanced regio- and enantioselectivity as well as new substrate acceptance. The obtained information and knowledge is useful for further engineering of P450pyr for other hydroxylations and oxidations. PMID:26507217

  1. Enzymes as Green Catalysts for Precision Macromolecular Synthesis.

    PubMed

    Shoda, Shin-Ichiro; Uyama, Hiroshi; Kadokawa, Jun-Ichi; Kimura, Shunsaku; Kobayashi, Shiro

    2016-02-24

    The present article comprehensively reviews the macromolecular synthesis using enzymes as catalysts. Among the six main classes of enzymes, the three classes, oxidoreductases, transferases, and hydrolases, have been employed as catalysts for the in vitro macromolecular synthesis and modification reactions. Appropriate design of reaction including monomer and enzyme catalyst produces macromolecules with precisely controlled structure, similarly as in vivo enzymatic reactions. The reaction controls the product structure with respect to substrate selectivity, chemo-selectivity, regio-selectivity, stereoselectivity, and choro-selectivity. Oxidoreductases catalyze various oxidation polymerizations of aromatic compounds as well as vinyl polymerizations. Transferases are effective catalysts for producing polysaccharide having a variety of structure and polyesters. Hydrolases catalyzing the bond-cleaving of macromolecules in vivo, catalyze the reverse reaction for bond forming in vitro to give various polysaccharides and functionalized polyesters. The enzymatic polymerizations allowed the first in vitro synthesis of natural polysaccharides having complicated structures like cellulose, amylose, xylan, chitin, hyaluronan, and chondroitin. These polymerizations are "green" with several respects; nontoxicity of enzyme, high catalyst efficiency, selective reactions under mild conditions using green solvents and renewable starting materials, and producing minimal byproducts. Thus, the enzymatic polymerization is desirable for the environment and contributes to "green polymer chemistry" for maintaining sustainable society. PMID:26791937

  2. One-Step Synthesis of Self-Supported Nickel Phosphide Nanosheet Array Cathodes for Efficient Electrocatalytic Hydrogen Generation.

    PubMed

    Wang, Xiaoguang; Kolen'ko, Yury V; Bao, Xiao-Qing; Kovnir, Kirill; Liu, Lifeng

    2015-07-01

    Nickel phosphide is an emerging low-cost, earth-abundant catalyst that can efficiently reduce water to generate hydrogen. However, the synthesis of nickel phosphide catalysts usually involves multiple steps and is laborious. Herein, a convenient and straightforward approach to the synthesis of a three-dimensional (3D) self-supported biphasic Ni5 P4 -Ni2 P nanosheet (NS) array cathode is presented, which is obtained by direct phosphorization of commercially available nickel foam using phosphorus vapor. The synthesized 3D Ni5 P4 -Ni2 P-NS array cathode exhibits outstanding electrocatalytic activity and long-term durability toward the hydrogen evolution reaction (HER) in acidic medium. The fabrication procedure reported here is scalable, showing substantial promise for use in water electrolysis. More importantly, the approach can be readily extended to synthesize other self-supported transition metal phosphide HER cathodes. PMID:26032688

  3. Synthesis of a Sulfonated Two-Dimensional Covalent Organic Framework as an Efficient Solid Acid Catalyst for Biobased Chemical Conversion.

    PubMed

    Peng, Yongwu; Hu, Zhigang; Gao, Yongjun; Yuan, Daqiang; Kang, Zixi; Qian, Yuhong; Yan, Ning; Zhao, Dan

    2015-10-12

    Because of limited framework stability tolerance, de novo synthesis of sulfonated covalent organic frameworks (COFs) remains challenging and unexplored. Herein, a sulfonated two-dimensional crystalline COF, termed TFP-DABA, was synthesized directly from 1,3,5-triformylphloroglucinol and 2,5-diaminobenzenesulfonic acid through a previously reported Schiff base condensation reaction, followed by irreversible enol-to-keto tautomerization, which strengthened its structural stability. TFP-DABA is a highly efficient solid acid catalyst for fructose conversion with remarkable yields (97 % for 5-hydroxymethylfurfural and 65 % for 2,5-diformylfuran), good chemoselectivity, and good recyclability. The present study sheds light on the de novo synthesis of sulfonated COFs as novel solid acid catalysts for biobased chemical conversion. PMID:26448524

  4. An efficient synthesis of iminoquinones by a chemoselective domino ortho-hydroxylation/oxidation/imidation sequence of 2-aminoaryl ketones.

    PubMed

    Chandrasekar, Selvaraj; Sekar, Govidasamy

    2016-03-21

    An efficient chemoselective domino oxidative homocoupling of 2-aminoaryl ketones in the presence of 2-iodoxybenzoic acid (IBX) for the synthesis of iminoquinone has been developed. The domino reaction proceeds via three consecutive steps, such as domino ortho-hydroxylation of 2-aminoaryl ketones, oxidation of a phenol derivative to benzoquinone and dimerization through imine formation to yield iminoquinone. Importantly, this reaction allows the recycling of the oxidant IBX by recovering the by-product iodosobenzoic acid (IBA) and oxidizing it back to IBX. A four step domino strategy for the synthesis of iminoquinone through in situ generation of 2-amino benzophenone from (2-amino phenyl)(phenyl)methanol was also developed. PMID:26891598

  5. Efficient and regioselective synthesis of globotriose by a novel α-galactosidase from Bacteroides fragilis.

    PubMed

    Gong, Wei; Xu, Li; Gu, Guofeng; Lu, Lili; Xiao, Min

    2016-08-01

    Globotriose (Galα1-4Galβ1-4Glc) is an important cell surface epitope that acts as the receptor for Shiga-like toxins, and it is also the core structure of Globo H and SSEA4 that are tumor-associated glycans. Hence, the enzymatic synthesis of globotriose would be necessary for the development of carbohydrate-based therapeutics for bacterial infections and cancers. Here, a novel GH27 α-galactosidase gene (agaBf3S), a 1521-bp DNA encoding 506 amino acids with a calculated molecular mass of 57.7 kDa, from Bacteroides fragilis NCTC9343 was cloned and heterogeneously expressed in Escherichia coli. The recombinant enzyme AgaBf3S preferentially hydrolyzed p-nitrophenyl-α-D-galactopyranoside (pNPαGal) in all tested nitrophenyl glycosides. It showed maximum activity at pH 4.5 and 40 °C, and it was stable at pH 4.0-11.0 below 40 °C and metal-independent. The K m and k cat values for pNPαGal, melibiose, and globotriose were 1.27 mM and 172.97 S(-1), 62.76 mM and 17.74 S(-1), and 4.62 mM and 388.45 S(-1), respectively. AgaBf3S could transfer galactosyl residue from pNPαGal to lactose (Galβ1-4Glc) with high efficiency and strict α1-4 regioselectivity. The effects of initial substrate concentration, pH, temperature, and reaction time on transglycosylation reaction catalyzed by AgaBf3S were studied in detail. AgaBf3S could synthesize globotriose as a single transglycosylation product with a maximum yield of 32.4 % from 20 mM pNPαGal and 500 mM lactose (pH 4.5) at 40 °C for 30 min. This new one-enzyme one-step synthetic reaction is simple, fast, and low cost, which provides a promising alternative to the current synthetic methods for access to pharmaceutically important Galα1-4-linked oligosaccharides. PMID:27020280

  6. Protease-catalyzed peptide synthesis using inverse substrates: the influence of reaction conditions on the trypsin acyl transfer efficiency.

    PubMed

    Schellenberger, V; Jakubke, H D; Zapevalova, N P; Mitin, Y V

    1991-06-01

    Benzyloxycarbonyl-L-alanine p-guanidinophenyl ester behaves as a trypsin "inverse substrate," i.e., a cationic center is included in the leaving group instead of being in the acyl moiety. Using this substrate as an acyl donor, trypsin catalyzes the synthesis of peptide bonds that cannot be split by this enzyme. An optimal acyl transfer efficiency was achieved between pH 8 and 9 at 30 degrees C.The addition of as much as 50% cosolvent was shown to be of minor influence on the acyl transfer efficiency, whereas the reaction velocity decreases by more than one order of magnitude. The efficiency of H-Leu-NH(2) and H-Val-NH(2) in deacylation is almost the same for "inverse" and normal type substrates. PMID:18600704

  7. Microorganisms as efficient biosystem for the synthesis of metal nanoparticles: current scenario and future possibilities.

    PubMed

    Salunke, Bipinchandra K; Sawant, Shailesh S; Lee, Sang-Ill; Kim, Beom Soo

    2016-05-01

    Nanoparticles, the elementary structures of nanotechnology, are important materials for fundamental studies and variety of applications. The different sizes and shapes of these materials exhibit unique physical and chemical properties than their bulk materials. There is a great interest in obtaining well-dispersed, ultrafine, and uniform nanoparticles to delineate and utilize their distinct properties. Nanoparticle synthesis can be achieved through a wide range of materials utilizing a number of methods including physical, chemical, and biological processes with various precursors from liquids and solids. There is a growing need to prepare environmentally friendly nanoparticles that do not produce toxic wastes in their process synthesis protocol. This kind of synthesis can be achieved by green environment benign processes, which happen to be mostly of a biological nature. Microorganisms are one of the most attractive and simple sources for the synthesis of different types of nanoparticles. This review is an attempt to provide the up-to-date information on current status of nanoparticle synthesis by different types of microorganisms such as fungi, yeast, bacteria, cyanobacteria, actinomycete, and algae. The probable biosynthesis mechanism and conditions for size/shape control are described. Various applications of microbially synthesized nanoparticles are summarized. They include antibacterial, antifungal, anticancer, larvicidal, medical imaging, biosensor, and catalytic applications. Finally, limitations and future prospects for specific research are discussed. PMID:27038958

  8. Stereoselectivity in the oxidation of bufuralol, a chiral substrate, by human cytochrome P450s.

    PubMed

    Narimatsu, Shizuo; Takemi, Chie; Kuramoto, Shino; Tsuzuki, Daisuke; Hichiya, Hiroyuki; Tamagake, Keietsu; Yamamoto, Shigeo

    2003-05-01

    Bufuralol (BF), a nonselective beta-adrenoceptor blocking agent, has a chiral center in its molecule, yielding the enantiomers 1'R-BF and 1'S-BF. beta-Adrenoceptor blocking potency is much higher in 1'S-BF than in 1'R-BF. One of the metabolic pathways of BF is 1"-hydroxylation of an ethyl group attached at the aromatic 7-position forming a carbinol metabolite (1"-hydroxybufuralol, 1"-OH-BF), and further oxidation (or dehydrogenation) produces a ketone metabolite (1-oxobufuralol, 1"-Oxo-BF). Both 1"-OH-BF and 1"-Oxo-BF are known to have beta-adrenoceptor blocking activities comparable to or higher than those of the parent drug. The 1"-hydroxylation introduces another chiral center into the BF molecule and four 1"-OH-BF diastereomers are formed from BF racemate in mammals, including humans, making elucidation of the metabolic profiles complicated. HPLC methods employing derivatization, reversed phase, or chiral columns have been developed to efficiently separate the four 1"-OH-BF diastereomers formed from BF enantiomers or racemate. Accumulated in vitro experimental results revealed that 1'R-BF is a much more preferential substrate than 1'S-BR for BF 1"-hydroxylation in human liver microsomes. Kinetic studies using recombinant human cytochrome P450 (CYP) enzymes indicate that CYP2D6 serves as a major BF 1"-hydroxylase and that CYP1A2 and CYP2C19 also contribute to BF 1"-hydroxylation in human livers. This mini-review summarizes the knowledge reported so far on the pharmacology of BF and its metabolites and the profiles of BF metabolism, especially focusing on the stereoselectivity in the oxidation of BF mainly in human livers and recombinant CYP enzymes. PMID:12666241

  9. Photochemistry and stereoselectivity of cellular retinaldehyde-binding protein from bovine retina

    SciTech Connect

    Saari, J.C.; Bredberg, D.L.

    1987-06-05

    11-cis-Retinaldehyde bound to cellular retinaldehyde-binding protein (CRALBP) is unaffected in bovine eyecup preparations by illumination that bleaches approximately 70% of the rhodopsin. Illumination of retinal homogenates to which CRALBP X (/sup 3/H)11-cis-retinaldehyde had been added did not result in a reduction of the specific activity of recovered 11-cis-retinaldehyde, ruling out a bleaching regeneration cycle. The quantum efficiency of photoisomerization for CRALBP X 11-cis-retinaldehyde was determined by comparing the rate of photoisomerization of 11-cis-retinaldehyde bound to purified CRALBP and opsin. The low value obtained (0.07), coupled with a low molar extinction coefficient (15,400 M-1 cm-1), results in a photosensitivity only about 4% that of rhodopsin. CRALBP binds 9-cis- and 11-cis-retinaldehyde, producing complexes with absorption maxima at 405 and 425 nm, respectively. No complexes were detected with 13-cis- and all-trans-retinaldehyde. Following incubation of CRALBP X 11-cis-retinol with an equimolar mixture of 9-, 11-, 13-cis-, and all-trans-retinaldehydes, only 11-cis-retinaldehyde and residual 11-cis-retinol are present on the protein following separation from excess retinoids. A similar result is obtained following incubation of CRALBP X 11-cis-retinol with mixtures of 9- and 11-cis-retinaldehyde ranging in composition from 9:1 to 1:9 (9-cis-:11-cis-,mol/mol). The results indicate that CRALBP X 11-cis-retinol is sufficiently stereoselective in its binding properties to warrant consideration as a component of the mechanism for the generation of 11-cis-retinaldehyde in the dark.

  10. Photochemistry and stereoselectivity of cellular retinaldehyde-binding protein from bovine retina.

    PubMed

    Saari, J C; Bredberg, D L

    1987-06-01

    11-cis-Retinaldehyde bound to cellular retinaldehyde-binding protein (CRALBP) is unaffected in bovine eyecup preparations by illumination that bleaches approximately 70% of the rhodopsin. Illumination of retinal homogenates to which CRALBP X [3H]11-cis-retinaldehyde had been added did not result in a reduction of the specific activity of recovered 11-cis-retinaldehyde, ruling out a bleaching regeneration cycle. The quantum efficiency of photoisomerization for CRALBP X 11-cis-retinaldehyde was determined by comparing the rate of photoisomerization of 11-cis-retinaldehyde bound to purified CRALBP and opsin. The low value obtained (0.07), coupled with a low molar extinction coefficient (15,400 M-1 cm-1), results in a photosensitivity only about 4% that of rhodopsin. CRALBP binds 9-cis- and 11-cis-retinaldehyde, producing complexes with absorption maxima at 405 and 425 nm, respectively. No complexes were detected with 13-cis- and all-trans-retinaldehyde. Following incubation of CRALBP X 11-cis-retinol with an equimolar mixture of 9-, 11-, 13-cis-, and all-trans-retinaldehydes, only 11-cis-retinaldehyde and residual 11-cis-retinol are present on the protein following separation from excess retinoids. A similar result is obtained following incubation of CRALBP X 11-cis-retinol with mixtures of 9- and 11-cis-retinaldehyde ranging in composition from 9:1 to 1:9 (9-cis-:11-cis-,mol/mol). The results indicate that CRALBP X 11-cis-retinol is sufficiently stereoselective in its binding properties to warrant consideration as a component of the mechanism for the generation of 11-cis-retinaldehyde in the dark. PMID:3584132

  11. Collagen synthesis promoting pullulan-PEI-ascorbic acid conjugate as an efficient anti-cancer gene delivery vector.

    PubMed

    Ambattu, Lizebona August; Rekha, M R

    2015-08-01

    Cationized pullulan (pullulan-PEI; PP) was synthesized and further modified with an anti-oxidant molecule, ascorbic acid (PPAA) at various ratios. The nanoplexes formed at an optimum ratio of 4:1 was within a size of 150nm and had a zeta potential of 9-14mV. The nanoplexes at this ratio was used for further investigations. The cell internalization and transfection efficiency of these nanoplexes were determined in presence of serum. The internalization and transfection efficiency were found to be unaffected by the presence of fetal bovine serum. Another interesting observation was that this polymer was found to have collagen synthesis promoting property. The collagen synthesis effect of these polymers was quantified and observed that PPAA3 promoted the highest. Transfection efficiency was evaluated by assessing the p53 gene expression in C6 rat glioma cells and cell death was quantified to be 96% by flow cytometry, thus establishing the high efficacy of this polymer. PMID:25933522

  12. A versatile and efficient synthesis of bithiophene-based dicarboxaldehydes from a common synthon.

    PubMed

    Bhuwalka, Achala; Mike, Jared F; Intemann, Jeremy J; Ellern, Arkady; Jeffries-El, Malika

    2015-09-28

    Bithiophene dicarboxaldehydes are promising electron-rich building blocks for the development of arylene vinylene-based organic semiconductors, but their use has been limited due to their synthetic inaccessibility. To facilitate the facile synthesis of these compounds we have prepared a novel functional bithiophene, namely 2,2'-(3,3'-dibromo-[2,2'-bithiophene]-5,5'-diyl)bis(5,5-dimethyl-1,3-dioxane) in two high yielding steps from 3,3',5,5'-tetrabromo-2,2'-bithiophene. This synthon is readily transformed into variety of bithiophene-based dicarboxaldehydes, also in high yields. The use of these functional molecules in the synthesis of arylene vinylene-linked donor-acceptor copolymers is demonstrated by the synthesis of two copolymers with electron deficient benzobisazoles. PMID:26248770

  13. Prins-Type Macrocyclizations as an Efficient Ring-Closing Strategy in Natural Product Synthesis

    PubMed Central

    Crane, Erika A.; Scheidt, Karl A.

    2011-01-01

    Prins-type macrocyclizations have recently emerged as a successful strategy in the synthesis of polyketide-derived natural products. This reaction provides a concise and selective means to form tetrahydropyran-containing macrocyclic rings of varying size. A high degree of functionality within the macrocycle is tolerated and the yields for these transformations are typically good to excellent. Since the initial report of a Prins macrocyclization reaction in 1979, examples of this approach did not re-emerge until 2008. However, the use of this method in natural product synthesis has rapidly gained momentum in the synthetic community, with multiple examples of this macrocyclization tactic reported in the recent literature. PMID:20931580

  14. Exploiting Pseudo C2-Symmetry for an Efficient Synthesis of the F-Ring of the Spongistatins

    PubMed Central

    Tanis, Paul S.; Infantine, Joshua R.; Leighton, James L.

    2013-01-01

    A concise and efficient synthesis of the F-ring fragment of the potent anti-mitotic marine macrolide spongistatin 1 has been developed. The key sequence involves double cross-metathesis/Sharpless asymmetric dihydroxylation reactions to establish four stereocenters in a pseudo C2-symmetric array, followed by a selective protection reaction that breaks the pseudo-symmetry, establishes a fifth stereocenter, and effectively differentiates the ester termini. Overall, the six contiguous stereocenters in the C(37)–C(45) F-ring fragment are established in just seven steps. PMID:24111885

  15. Efficient and green synthesis of tetrasubstituted pyrroles promoted by task-specific basic ionic liquids as catalyst in aqueous media.

    PubMed

    Yavari, Issa; Kowsari, Elaheh

    2009-11-01

    Synthesis of tetrasubstituted pyrroles by the three-component condensation reaction of acid chlorides, dialkyl acetylenedicarboxylates, and amino acids in the presence of various room-temperature ionic liquids (RTILs) as catalysts in water is reported. Among the ionic liquids used, the basic functionalized ionic liquid, butyl methyl imidazolium hydroxide [bmim]OH, was the most effective catalyst. The influence of reaction temperature, reaction time, and amount of ionic liquid on the reaction was investigated. The [bmim]OH/H(2)O catalyst system could be reused for at least five recycles without appreciable loss of efficiency. PMID:19381850

  16. Highly enantioselective and efficient synthesis of flavanones including pinostrobin through the rhodium-catalyzed asymmetric 1,4-addition.

    PubMed

    Korenaga, Toshinobu; Hayashi, Keigo; Akaki, Yusuke; Maenishi, Ryota; Sakai, Takashi

    2011-04-15

    An efficient synthesis of bioactive chiral flavanones (1) was achieved through the Rh-catalyzed asymmetric 1,4-addition of arylboronic acid to chromone. The reaction in toluene proceeded smoothly at room temperature in the presence of 0.5% Rh catalyst with electron-poor chiral diphosphine MeO-F(12)-BIPHEP. In this reaction, the 1,2-addition to (S)-1 frequently occurred to yield (2S,4R)-2,4-diaryl-4-chromanol as a byproduct, which could be reduced by changing the reaction solvent to CH(2)Cl(2) to deactivate the Rh catalyst (3% required). PMID:21413690

  17. Stereoselectivity of nitrile oxide cycloadditions to chiral allylic fluorides: experiment and theory.

    PubMed

    Prakesch, Michael; Grée, Danielle; Grée, René; Carter, Jennifer; Washington, Ilyas; Houk, K N

    2003-11-21

    The cycloadditions of nitrile oxides with new and previously studied allylic fluorides were examined. The 1,3-dipolar cycloaddition reactions were also investigated theoretically with density functional theory (B3LYP) based transition-state modelling. The predictions provided reasonable agreement with experiment, indicating that both steric and electronic effects have important influences on the stereoselectivities of these reactions. PMID:14639650

  18. Applying Symmetries of Common Objects to Help Students Understand Stereoselectivity for Apparently Symmetric Substrates

    ERIC Educational Resources Information Center

    Jittam, Piyachat; Ruenwongsa, Pintip; Panijpan, Bhinyo

    2008-01-01

    We have found it an effective way of teaching symmetry in the context of stereoselectivity, to use common everyday objects with the same point groups as the substrates involved. This has helped students to distinguish between those symmetry elements which allow for stereospecificity and those which preclude it. Two symmetry elements, the simple…

  19. Stereoselective access to tubuphenylalanine and tubuvaline: improved Mn-mediated radical additions and assembly of a tubulysin tetrapeptide analog.

    PubMed

    Friestad, Gregory K; Banerjee, Koushik; Marié, Jean-Charles; Mali, Umesh; Yao, Lei

    2016-04-01

    Synthesis of tubuphenylalanine and tubuvaline (Tuv), α-substituted γ-amino acid building blocks for tubulysin family of antimitotic compounds, has been improved using a radical addition reaction in the presence of unprotected hydroxyl functionality. The key carbon-carbon bond construction entails stereoselective Mn-mediated photolytic additions of alkyl iodides to the C=N bond of chiral N-acylhydrazones, and generates the chiral amines in high yield with complete stereocontrol. Reductive N-N bond cleavage and alcohol oxidation converted these amino alcohols into the corresponding γ-amino acids. The route to Tuv proceeded via peptide coupling with serine methyl ester, followed by a high-yielding sequence to convert the serine amide to a thiazole. Finally, peptide bond construction established the tubulysin framework in the form of a C-terminal alcohol analog. Attempted oxidation to the C-terminal carboxylate was unsuccessful; control experiments with dipeptide 18 showed a cyclization interfered with the desired oxidation process. PMID:26883395

  20. Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation.

    PubMed

    Almaqwashi, Ali A; Andersson, Johanna; Lincoln, Per; Rouzina, Ioulia; Westerlund, Fredrik; Williams, Mark C

    2016-03-29

    DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [μ-dppzip(phen)4Ru2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)2dppz) and the distal subunit (Ru(phen)2ip), respectively, each of which can be either right-handed (Δ) or left-handed (Λ). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Δxeq, and the dynamic DNA structural deformations during ligand association xon and dissociation xoff. We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a Kd of 27 ± 3 nM for (Δ,Λ)-Piz to a Kd of 622 ± 55 nM for (Λ,Δ)-Piz. The striking affinity decrease is correlated with increasing Δxeq from 0.30 ± 0.02 to 0.48 ± 0.02 nm and xon from 0.25 ± 0.01 to 0.46 ± 0.02 nm, but limited xoff changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics. PMID:27028636

  1. Facile synthesis of iron phosphide nanorods for efficient and durable electrochemical oxygen evolution.

    PubMed

    Xiong, Dehua; Wang, Xiaoguang; Li, Wei; Liu, Lifeng

    2016-07-01

    Iron phosphide (FeP) nanorods have been fabricated by a facile hydrothermal synthesis of iron oxyhydroxide precursors, followed by a convenient phosphorization process. The FeP nanorods dispersed on carbon fiber paper current collectors exhibit outstanding catalytic activity and excellent long-term stability toward the oxygen evolution reaction (OER). PMID:27333123

  2. Efficient room-temperature synthesis of a highly strained carbon nanohoop fragment of buckminsterfullerene

    NASA Astrophysics Data System (ADS)

    Evans, Paul J.; Darzi, Evan R.; Jasti, Ramesh

    2014-05-01

    Warped carbon-rich molecules have captured the imagination of scientists across many disciplines. Owing to their promising materials properties and challenging synthesis, strained hydrocarbons are attractive targets that push the limits of synthetic methods and molecular design. Herein we report the synthesis and characterization of [5]cycloparaphenylene ([5]CPP), a carbon nanohoop that can be envisaged as an open tubular fragment of C60, the equator of C70 fullerene and the unit cycle of a [5,5] armchair carbon nanotube. Given its calculated 119 kcal mol-1 strain energy and severely distorted benzene rings, this synthesis, which employs a room-temperature macrocyclization of a diboronate precursor, single-electron reduction and elimination, is remarkably mild and high yielding (27% over three steps). Single-crystal X-ray diffraction data were obtained to confirm its geometry and previously disputed benzenoid character. First and second pseudoreversible oxidation and reduction events were observed via cyclic voltammetry. The ease of synthesis, high solubility and narrowest optical HOMO/LUMO gap of any para-polyphenylene synthesized make [5]CPP a desirable new material for organic electronics.

  3. Rapid microwave synthesis of indium filled skutterudites: An energy efficient route to high performance thermoelectric materials

    SciTech Connect

    Biswas, Krishnendu; Muir, Sean; Subramanian, M.A.

    2011-12-15

    Graphical abstract: Filled skutterudites are promising thermoelectric materials. We report the microwave assisted synthesis of CoSb{sub 3} and In{sub 0.2}Co{sub 4}Sb{sub 12}. This method reduces the calcination time for skutterudite phase formation from 2 days to 2 min, thereby significantly reducing the time and energy needed to produce materials suitable for property and device testing. Highlights: Black-Right-Pointing-Pointer The microwave assisted solid state synthesis of CoSb{sub 3} and In{sub 0.2}Co{sub 4}Sb{sub 12} is reported. Black-Right-Pointing-Pointer This method allows the calcination time to be reduced from 2 days to 2 min. Black-Right-Pointing-Pointer Physical properties of microwave samples match those prepared conventionally. -- Abstract: Filled skutterudites are promising thermoelectric materials due to reduced thermal conductivity upon inserting a guest atom or 'rattler' into the CoSb{sub 3} structure. By using an indium rattler dimensionless Figure of Merit (ZT) values >1 at 650 K have been reported. The conventional synthesis of these compounds typically takes several days ({approx}3 days) to obtain the final well-sintered material for property measurements. We report here a microwave-assisted synthesis method that reduces the initial calcination time from 2 days to 2 min. This route significantly reduces the time needed to produce materials suitable for property and device testing.

  4. Stereoselective pharmacokinetics and metabolism of the enantiomers of cyclophosphamide. Preliminary results in humans and rabbits.

    PubMed

    Holm, K A; Kindberg, C G; Stobaugh, J F; Slavik, M; Riley, C M

    1990-04-15

    [R(+),S(-)]-Cyclophosphamide [(R,S)-CP] is an anticancer drug, containing a chiral phosphorous atom, which is prepared and used clinically as the racemic mixture. A new high-performance liquid chromatographic assay suitable for pharmacokinetic studies of CP enantiomers in plasma has been reported recently by this laboratory (Reid et al., Anal Chem 61: 441-446, 1989). Briefly, the assay involves ethyl acetate extraction of CP enantiomers from plasma followed by derivatization to diastereomers in a two-step process utilizing chloral and (+)-naproxen acid chloride. Chromatographic analysis was performed on a reversed phase (ODS) column with detection at 232 nm. In the present study, preliminary results on the applicability of this assay to pharmacokinetic studies are presented. Several rabbits were used to compare the influence of i.p., i.v., and oral routes of administration on the stereoselective disposition of (R,S)-CP. Following i.p. administration, S-CP was cleared faster than R-CP. Following oral administration, only R-CP was detectable in plasma, while i.v. administration resulted in minor or no stereoselective disposition. These results indicated that there was a marked stereoselective metabolism of the S-CP enantiomer, with the i.p. and oral routes producing the greatest differences due to first-pass metabolism. Incubation of rabbit-liver microsomes with (R,S)-CP demonstrated that the monooxygenase system can exhibit marked stereoselectivity in its metabolism of CP. The ratio of R-CP to S-CP in the incubation medium increased during the incubation period from 1:1 initially to 4.5:1 after 60 min. The results from the experiments with rabbits indicate that the first-pass metabolism of this drug is highly stereoselective; in contrast, cancer patients who had received (R,S)-CP as an i.v. infusion showed no stereoselectivity in the elimination of the enantiomers. Pharmacokinetic studies with cancer patients, receiving (R,S)-CP as an oral dose, are in progress in

  5. Highly efficient synthesis of endomorphin-2 under thermodynamic control catalyzed by organic solvent stable proteases with in situ product removal.

    PubMed

    Xu, Jiaxing; Sun, Honglin; He, Xuejun; Bai, Zhongzhong; He, Bingfang

    2013-02-01

    An efficient enzymatic synthesis of endomorphin-2 (EM-2) was achieved using organic solvent stable proteases in nonaqeous media, based on thermodynamic control and an in situ product removal methodology. The high stability of biocatalysts in organic solvents enabled the aleatoric modulation of the nonaqueous reaction media to shift thermodynamic equilibrium toward synthesis. Peptide Boc-Phe-Phe-NH2 was synthesized with a high yield of 96% by the solvent stable protease WQ9-2 in monophase medium with an economical molar ratio of the substrate of 1:1. The tetrapeptide Boc-Tyr-Pro-Phe-Phe-NH2 was synthesized with a yield of 88% by another organic solvent tolerant protease PT121 from Boc-Tyr-Pro-OH and Phe-Phe-NH2 in an organic-aqueous biphasic system. The reaction-separation coupling in both enzymatic processes provides "driving forces" for the synthetic reactions and gives a high yield and high productivity without purification of the intermediate, thereby making the synthesis more amenable to scale-up. PMID:23305895

  6. Efficient Cu(OTf)2-catalyzed synthesis of novel and diverse 2,3-dihydroquinazolin-4(1H)-ones.

    PubMed

    Zhu, Xiaoyan; Kang, So Rang; Xia, Likai; Lee, Jihye; Basavegowda, Nagaraj; Lee, Yong Rok

    2015-02-01

    An efficient one-pot synthesis of various 2,3-dihydroquinazolin-4(1H)-one derivatives was accomplished using Cu(OTf)2-catalyzed multi-component reactions between isatoic anhydride, ketones, and amines. The method has several significant advantages; mild reaction conditions, easy handling, and efficiency of catalyst. PMID:25403260

  7. Synthetic Studies on Et-743. Assembly of the Pentacyclic Core and a Formal Total Synthesis

    PubMed Central

    Fishlock, Dan; Williams, Robert M.

    2009-01-01

    A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule. PMID:18687003

  8. Total Synthesis of (±)-Integrifolin.

    PubMed

    Shimomaki, Katsuya; Kusama, Hiroyuki; Iwasawa, Nobuharu

    2016-07-11

    The total synthesis of (±)-integrifolin has been achieved for the first time through the stereoselective preparation of the bicyclo[5.3.0]decane skeleton based on the tungsten-catalyzed cyclization of acyclic trienynes under photoirradiation conditions. Further key transformations of the cyclized product are the Tamao oxidation through cyclic silyl ether, the introduction of two oxygen functionalities by the oxidation of the diene and the construction of three exo-methylene moieties. PMID:27147582

  9. Direct Catalytic Asymmetric Mannich Reaction with Dithiomalonates as Excellent Mannich Donors: Organocatalytic Synthesis of (R)-Sitagliptin.

    PubMed

    Bae, Han Yong; Kim, Mun Jong; Sim, Jae Hun; Song, Choong Eui

    2016-08-26

    In this study, dithiomalonates (DTMs) were demonstrated to be exceptionally efficient Mannich donors in terms of reactivity and stereoselectivity in cinchona-based-squaramide-catalyzed enantioselective Mannich reactions of diverse imines or α-amidosulfones as imine surrogates. Owing to the superior reactivity of DTMs as compared to conventional malonates, the catalyst loading could be reduced to 0.1 mol % without the erosion of enantioselectivity (up to 99 % ee). Furthermore, by the use of a DTM, even some highly challenging primary alkyl α-amidosulfones were smoothly converted into the desired adducts with excellent enantioselectivity (up to 97 % ee), whereas the use of a malonate or monothiomalonate resulted in no reaction under identical conditions. The synthetic utility of the chiral Mannich adducts obtained from primary alkyl substrates was highlighted by the organocatalytic, coupling-reagent-free synthesis of the antidiabetic drug (-)-(R)-sitagliptin. PMID:27486059

  10. Energy- and carbon-efficient synthesis of functionalized small molecules in bacteria using non-decarboxylative Claisen condensation reactions.

    PubMed

    Cheong, Seokjung; Clomburg, James M; Gonzalez, Ramon

    2016-05-01

    Anabolic metabolism can produce an array of small molecules, but yields and productivities are low owing to carbon and energy inefficiencies and slow kinetics. Catabolic and fermentative pathways, on the other hand, are carbon and energy efficient but support only a limited product range. We used carbon- and energy-efficient non-decarboxylative Claisen condensation reactions and subsequent β-reduction reactions, which can accept a variety of functionalized primers and functionalized extender units and operate in an iterative manner, to synthesize functionalized small molecules. Using different ω- and ω-1-functionalized primers and α-functionalized extender units in combination with various termination pathways, we demonstrate the synthesis of 18 products from 10 classes, including ω-phenylalkanoic, α,ω-dicarboxylic, ω-hydroxy, ω-1-oxo, ω-1-methyl, 2-methyl, 2-methyl-2-enolic and 2,3-dihydroxy acids, β-hydroxy-ω-lactones, and ω-1-methyl alcohols. PMID:27088721

  11. Evaluation of the stereoselective biotransformation of permethrin in human liver microsomes: contributions of cytochrome P450 monooxygenases to the formation of estrogenic metabolites.

    PubMed

    Lavado, Ramon; Li, Jiwen; Rimoldi, John M; Schlenk, Daniel

    2014-04-21

    Permethrin (PM) is a pyrethroid insecticide that exists as 4 enantiomers. Biotransformation of PM to estrogen receptor agonists (3-phenoxybenzyl alcohol (PBOH) and 3-(4'-hydroxyphenoxy)-benzyl alcohol (3,4 PBOH)) has been shown to be stereoselective in other vertebrate species. This study evaluated the biotransformation of PM enantiomers in human liver microsomes and with recombinant CYP3A4 and CYP2C19. PBOH and 3,4 PBOH were the only metabolites detected from in vitro incubations including each of the 4 enantiomers of PM with 1R-trans PM having the most efficient NADPH-catalyzed biotransformation to both metabolites. Coincubation with the CYP inhibitor ketoconazole and time course experiments with liver microsomes and recombinant CYP2C19 and CYP3A4 indicated CYP-catalyzed stereoselective cleavage of the ester followed by 4-hydoxylation to 3,4' PBOH. These data indicate potential dispositional differences may occur with PM enantiomers and a shift in putative molecular targets. While cleavage of pyrethroid esters lead to detoxification of the acute neurological effects, formation of the benzyl alcohol and hydroxylated metabolite may lead to estrogenic responses, since each of these metabolites are estrogen receptor ligands. PMID:24548679

  12. Applied reaction dynamics: efficient synthesis gas production via single collision partial oxidation of methane to CO on Rh111.

    PubMed

    Gibson, K D; Viste, M; Sibener, S J

    2006-10-01

    Supersonic molecular beams have been used to determine the yield of CO from the partial oxidation of CH4 on a Rh111 catalytic substrate, CH4+12O2-->CO+2H2, as a function of beam kinetic energy. These experiments were done under ultrahigh vacuum conditions with concurrent molecular beams of O2 and CH4, ensuring that there was only a single collision for the CH4 to react with the surface. The fraction of CH4 converted is strongly dependent on the normal component of the incident beam's translational energy, and approaches unity for energies greater than approximately 1.3 eV. Comparison with a simplified model of the methane-Rh111 reactive potential gives insight into the barrier for methane dissociation. These results demonstrate the efficient conversion of methane to synthesis gas, CO+2H2, are of interest in hydrogen generation, and have the optimal stoichiometry for subsequent utilization in synthetic fuel production (Fischer-Tropsch or methanol synthesis). Moreover, under the reaction conditions explored, no CO2 was detected, i.e., the reaction proceeded with the production of very little, if any, unwanted greenhouse gas by-products. These findings demonstrate the efficacy of overcoming the limitations of purely thermal reaction mechanisms by coupling nonthermal mechanistic steps, leading to efficient C-H bond activation with subsequent thermal heterogeneous reactions. PMID:17029475

  13. Retention of OsNMD3 in the cytoplasm disturbs protein synthesis efficiency and affects plant development in rice.

    PubMed

    Shi, Yanyun; Liu, Xiangling; Li, Rui; Gao, Yaping; Xu, Zuopeng; Zhang, Baocai; Zhou, Yihua

    2014-07-01

    The ribosome is the basic machinery for translation, and biogenesis of ribosomes involves many coordinated events. However, knowledge about ribosomal dynamics in higher plants is very limited. This study chose a highly conserved trans-factor, the 60S ribosomal subunit nuclear export adaptor NMD3, to characterize the mechanism of ribosome biogenesis in the monocot plant Oryza sativa (rice). O. sativa NMD3 (OsNMD3) shares all the common motifs and shuttles between the nucleus and cytoplasm via CRM1/XPO1. A dominant negative form of OsNMD3 with a truncated nuclear localization sequence (OsNMD3(ΔNLS)) was retained in the cytoplasm, consequently interfering with the release of OsNMD3 from pre-60S particles and disturbing the assembly of ribosome subunits. Analyses of the transactivation activity and cellulose biosynthesis level revealed low protein synthesis efficiency in the transgenic plants compared with the wild-type plants. Pharmaceutical treatments demonstrated structural alterations in ribosomes in the transgenic plants. Moreover, global expression profiles of the wild-type and transgenic plants were investigated using the Illumina RNA sequencing approach. These expression profiles suggested that overexpression of OsNMD3(ΔNLS) affected ribosome biogenesis and certain basic pathways, leading to pleiotropic abnormalities in plant growth. Taken together, these results strongly suggest that OsNMD3 is important for ribosome assembly and the maintenance of normal protein synthesis efficiency. PMID:24723395

  14. Efficient end-capping synthesis of neutral donor-acceptor [2]rotaxanes under additive-free and mild conditions.

    PubMed

    Domoto, Yuya; Sase, Shohei; Goto, Kei

    2014-11-24

    Efficient end-capping synthesis of neutral donor-acceptor (D-A) [2]rotaxanes without loading any catalysts or activating agents was achieved by utilizing high reactivity of a pentacoordinated hydrosilane toward salicylic acid derivatives. As components of [2]rotaxanes, an electron-deficient naphthalenediimide-containing axle with a salicylic acid terminus and several electron-rich bis(naphthocrown) ether macrocycles were employed. End-capping reactions with the pentacoordinated hydrosilane underwent smoothly even at low temperature to afford the corresponding [2]rotaxanes in good yields. A [2]rotaxane containing bis-1,5-(dinaphtho)-38-crown-10 ether as a wheel molecule was synthesized and isolated in 84% yield by the end-capping at -10 °C, presenting the highest yield ever reported for the end-capping synthesis of a neutral D-A [2]rotaxane. It was found that the yields of the [2]rotaxanes in the end-capping reactions were almost parallel to the formation ratios of the corresponding pseudo[2]rotaxanes estimated by utilizing model systems. These results indicate that the end-capping reaction using the pentacoordinated hydrosilane proceeded without perturbing the threading process, and most of the pseudo[2]rotaxanes underwent efficient end-capping reaction even at low temperature. PMID:25284148

  15. Applied reaction dynamics: Efficient synthesis gas production via single collision partial oxidation of methane to CO on Rh(111)

    NASA Astrophysics Data System (ADS)

    Gibson, K. D.; Viste, M.; Sibener, S. J.

    2006-10-01

    Supersonic molecular beams have been used to determine the yield of CO from the partial oxidation of CH4 on a Rh(111) catalytic substrate, CH4+(1/2)O2→CO +2H2, as a function of beam kinetic energy. These experiments were done under ultrahigh vacuum conditions with concurrent molecular beams of O2 and CH4, ensuring that there was only a single collision for the CH4 to react with the surface. The fraction of CH4 converted is strongly dependent on the normal component of the incident beam's translational energy, and approaches unity for energies greater than ˜1.3eV. Comparison with a simplified model of the methane-Rh(111) reactive potential gives insight into the barrier for methane dissociation. These results demonstrate the efficient conversion of methane to synthesis gas, CO +2H2, are of interest in hydrogen generation, and have the optimal stoichiometry for subsequent utilization in synthetic fuel production (Fischer-Tropsch or methanol synthesis). Moreover, under the reaction conditions explored, no CO2 was detected, i.e., the reaction proceeded with the production of very little, if any, unwanted greenhouse gas by-products. These findings demonstrate the efficacy of overcoming the limitations of purely thermal reaction mechanisms by coupling nonthermal mechanistic steps, leading to efficient C-H bond activation with subsequent thermal heterogeneous reactions.

  16. The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain.

    PubMed

    Potisopon, Supanee; Priet, Stéphane; Collet, Axelle; Decroly, Etienne; Canard, Bruno; Selisko, Barbara

    2014-10-01

    Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis. PMID:25209234

  17. The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain

    PubMed Central

    Potisopon, Supanee; Priet, Stéphane; Collet, Axelle; Decroly, Etienne; Canard, Bruno; Selisko, Barbara

    2014-01-01

    Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis. PMID:25209234

  18. Resource-Efficient High-Yield Ionothermal Synthesis of Microcrystalline Cu3-xP.

    PubMed

    Wolff, Alexander; Pallmann, Julia; Boucher, Richard; Weiz, Alexander; Brunner, Eike; Doert, Thomas; Ruck, Michael

    2016-09-01

    Polycrystalline Cu3-xP was successfully synthesized in different ionic liquids comprising imidazolium and phosphonium cations. The reaction of elemental copper and red phosphorus in trihexyltetradecylphosphonium chloride at 200 °C led to single-phase Cu3-xP (x = 0.05) within 24 h with a quantitative yield (99%). Liquid-state nuclear magnetic resonance spectroscopy of the ionic liquids revealed degeneration of the imidazolium cations under the synthesis conditions, while phosphonium cations remain stable. The solid products were characterized with X-ray powder diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, solid-state nuclear magnetic resonance spectroscopy, and elemental analysis. A reinvestigation of the electronic transport properties of Cu2.95(4)P showed metallic behavior for the bulk material. The formation of CuP2 during the synthesis of phosphorus-rich Cu3-xP (x ≥ 0.1) was observed. PMID:27559933

  19. Efficient Synthesis of Primary Nitrocarbamates of Sugar Alcohols: From Food to Energetic Materials.

    PubMed

    Axthammer, Quirin J; Klapötke, Thomas M; Krumm, Burkhard

    2016-02-18

    The synthesis of various new polyvalent nitrocarbamates derived from sugar alcohols was accomplished by an economically benign two-step synthesis. The precursor carbamates were synthesized with the reagent chlorosulfonyl isocyanate (CSI) and further nitrated using mixed acid. The starting materials, sugar alcohols, are renewable biomass, mainly used in food and cosmetic industry. The structures of one carbamate and one nitrocarbamate were exemplary described by single-crystal X-ray-analysis. The heat of formation is calculated by the use of isodesmic reactions and the energetic performance data were estimated. All compounds were fully characterized by elemental analysis, vibrational spectroscopy, (1)H, (13)C, and (14/15)N NMR spectroscopy and thermal analysis (DSC). The nitrocarbamates exhibit good detonation performance and have significantly lower sensitivities compared to the commonly used nitrate ester explosive PETN. PMID:26633737

  20. Efficient One-Pot Synthesis of Colloidal Zirconium Oxide Nanoparticles for High-Refractive-Index Nanocomposites.

    PubMed

    Liu, Chao; Hajagos, Tibor Jacob; Chen, Dustin; Chen, Yi; Kishpaugh, David; Pei, Qibing

    2016-02-01

    Zirconium oxide nanoparticles are promising candidates for optical engineering, photocatalysis, and high-κ dielectrics. However, reported synthetic methods for the colloidal zirconium oxide nanoparticles use unstable alkoxide precursors and have various other drawbacks, limiting their wide application. Here, we report a facile one-pot method for the synthesis of colloidally stable zirconium oxide nanoparticles. Using a simple solution of zirconium trifluoroacetate in oleylamine, highly stable zirconium oxide nanoparticles have been synthesized with high yield, following a proposed amidization-assisted sol-gel mechanism. The nanoparticles can be readily dispersed in nonpolar solvents, forming a long-term stable transparent solution, which can be further used to fabricate high-refractive-index nanocomposites in both monolith and thin-film forms. In addition, the same method has also been extended to the synthesis of titanium oxide nanoparticles, demonstrating its general applicability to all group IVB metal oxide nanoparticles. PMID:26824518

  1. Ir-Cu nanoframes: one-pot synthesis and efficient electrocatalysts for oxygen evolution reaction.

    PubMed

    Pei, Jiajing; Mao, Junjie; Liang, Xin; Chen, Chen; Peng, Qing; Wang, Dingsheng; Li, Yadong

    2016-03-01

    Herein, we achieved successful synthesis of uniform Ir-Cu nanoframes with highly open structures by a facile one-pot strategy. The key to obtain alloy nanoframes was the careful control over the reduction and galvanic replacement reactions between different metals. The as-prepared Ir-Cu was proved to be an effective template for constructing trimetallic nanoframes. Furthermore, these highly open nanostructures exhibited excellent electrocatalytic performance toward oxygen evolution reaction in alkaline media. PMID:26864283

  2. Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers

    PubMed Central

    Kundu, Samir; Roy, Babli

    2014-01-01

    Summary The development of a silica-promoted highly selective synthesis of 1,2 or 1,3-dithioethers via solvent-free one-pot tandem reactions of an allyl bromide with excess thiol at room temperature is described. The choice of silica gel, either pre-calcined or moistened with water, exhibited notable regioselectivity in the formation of dithioethers. Plausible mechanistic routes were explored and postulated. PMID:24454561

  3. An Efficient Synthesis of (±)-Grandisol Featuring 1,5-Enyne Metathesis

    PubMed Central

    Graham, Thomas J. A.; Gray, Erin E.; Burgess, James M.; Goess, Brian C.

    2009-01-01

    An eight step synthesis of (±)-grandisol features a key sequence involving a high-yielding, microwave-assisted enyne metathesis to yield a 1-alkenylcyclobutene that is semihydrogenated to yield a silyl-protected grandisol. Metathesis catalyst screens revealed an intriguing trend whereby substrate conversion correlated strongly with the identity of the ligands on the catalyst. In addition, new reactivity of 1-alkenylcyclobutenes toward hydrogenation is described. PMID:19957923

  4. Highly efficient one-pot multienzyme (OPME) synthesis of glycans with fluorous-tag assisted purification.

    PubMed

    Hwang, Joel; Yu, Hai; Malekan, Hamed; Sugiarto, Go; Li, Yanhong; Qu, Jingyao; Nguyen, Van; Wu, Dongyuan; Chen, Xi

    2014-03-25

    Oligo(ethylene glycol)-linked light fluorous tags have been found to be optimal for conjugating to glycans for both high-yield enzymatic glycosylation reactions using one-pot multienzyme (OPME) systems and quick product purification using fluorous solid-phase extraction (FSPE) cartridges. The combination of OPME glycosylation systems and the FSPE cartridge purification scheme provides a highly effective strategy for facile synthesis and purification of glycans. PMID:24473465

  5. Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram.

    PubMed

    Huang, Linwei; Zhu, Jinbin; Jiao, Guangjun; Wang, Zheng; Yu, Xingxin; Deng, Wei-Ping; Tang, Wenjun

    2016-03-24

    Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram. PMID:26933831

  6. Ultrasound-assisted one-pot synthesis of substituted coumarins catalyzed by poly(4-vinylpyridinium) hydrogen sulfate as an efficient and reusable solid acid catalyst.

    PubMed

    Khaligh, Nader Ghaffari

    2013-07-01

    Poly(4-vinylpyridinium) hydrogen sulfate solid acid was found to be efficient catalyst for synthesis of substituted coumarins via Pechmann reaction using ultrasound irradiation at room temperature and neat condition in high yields with short reaction times. This methodology offers momentous improvements over various options for the synthesis of coumarins with regard to yield of products, simplicity in operation and green aspects by avoiding toxic catalysts and solvents. Further, the catalyst can be reused and recovered for several times. PMID:23395258

  7. Simple enzymatic procedure for L-carnosine synthesis: whole-cell biocatalysis and efficient biocatalyst recycling.

    PubMed

    Heyland, Jan; Antweiler, Nicolai; Lutz, Jochen; Heck, Tobias; Geueke, Birgit; Kohler, Hans-Peter E; Blank, Lars M; Schmid, Andreas

    2010-01-01

    β-Peptides and their derivates are usually stable to proteolysis and have an increased half-life compared with α-peptides. Recently, β-aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of β-peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole-cell biocatalyst for the synthesis and production of β-peptides using this enzymatic activity. For the optimization of the reaction system we chose the commercially relevant β,α-dipeptide L-carnosine (β-alanine-L-histidine) as model product. We were able to show that different recombinant yeast and bacteria strains, which overexpress a β-peptidase, could be used directly as whole-cell biocatalysts for the synthesis of L-carnosine. By optimizing relevant reaction conditions for the best-performing recombinant Escherichia coli strain, such as pH and substrate concentrations, we obtained high l-carnosine yields of up to 71%. Long-time as well as biocatalyst recycling experiments indicated a high stability of the developed biocatalyst for at least five repeated batches. Application of the recombinant E. coli in a fed-batch process enabled the accumulation of l-carnosine to a concentration of 3.7 g l(-1). PMID:21255308

  8. Templated synthesis of nickel nanoparticles: Toward heterostructured nanocomposites for efficient hydrogen storage

    SciTech Connect

    Nelson, Nicholas Cole

    2013-01-01

    The world is currently facing an energy and environmental crisis for which new technologies are needed. Development of cost-competitive materials for catalysis and hydrogen storage on-board motor vehicles is crucial to lead subsequent generations into a more sustainable and energy independent future. This thesis presents work toward the scalable synthesis of bimetallic heterostructures that can enable hydrogen to compete with carbonaceous fuels by meeting the necessary gravimetric and volumetric energy densities and by enhancing hydrogen sorption/desorption kinetics near ambient temperatures and pressures. Utilizing the well-known phenomenon of hydrogen spillover, these bimetallic heterostructures could work by lowering the activation energy for hydrogenation and dehydrogenation of metals. Herein, we report a novel method for the scalable synthesis of silica templated zero-valent nickel particles (Ni⊂SiO2) that hold promise for the synthesis of nickel nanorods for use in bimetallic heterostructures for hydrogen storage. Our synthesis proceeds by chemical reduction of a nickel-hydrazine complex with sodium borohydride followed by calcination under hydrogen gas to yield silica encapsulated nickel particles. Transmission electron microscopy and powder X-ray diffraction were used to characterize the general morphology of the resultant nanocapsules as well as the crystalline phases of the incorporated Ni0 nanocrystals. The structures display strong magnetic behavior at room temperature and preliminary data suggests nickel particle size can be controlled by varying the amount of nickel precursor used in the synthesis. Calcination under different environments and TEM analysis provides evidence for an atomic migration mechanism of particle formation. Ni⊂SiO2 nanocapsules were used as seeds to induce heterogeneous nucleation and subsequent growth within the nanocapsule via electroless nickel plating. Nickel nanoparticle growth occurs

  9. Templated synthesis of nickel nanoparticles: Toward heterostructured nanocomposites for efficient hydrogen storage

    NASA Astrophysics Data System (ADS)

    Nelson, Nicholas Cole

    The world is currently facing an energy and environmental crisis for which new technologies are needed. Development of cost-competitive materials for catalysis and hydrogen storage on-board motor vehicles is crucial to lead subsequent generations into a more sustainable and energy independent future. This thesis presents work toward the scalable synthesis of bimetallic heterostructures that can enable hydrogen to compete with carbonaceous fuels by meeting the necessary gravimetric and volumetric energy densities and by enhancing hydrogen sorption/desorption kinetics near ambient temperatures and pressures. Utilizing the well-known phenomenon of hydrogen spillover, these bimetallic heterostructures could work by lowering the activation energy for hydrogenation and dehydrogenation of metals. Herein, we report a novel method for the scalable synthesis of silica templated zero-valent nickel particles (Ni⊂SiO2) that hold promise for the synthesis of nickel nanorods for use in bimetallic heterostructures for hydrogen storage. Our synthesis proceeds by chemical reduction of a nickel-hydrazine complex with sodium borohydride followed by calcination under hydrogen gas to yield silica encapsulated nickel particles. Transmission electron microscopy and powder X-ray diffraction were used to characterize the general morphology of the resultant nanocapsules as well as the crystalline phases of the incorporated Ni0 nanocrystals. The structures display strong magnetic behavior at room temperature and preliminary data suggests nickel particle size can be controlled by varying the amount of nickel precursor used in the synthesis. Calcination under different environments and TEM analysis provides evidence for an atomic migration mechanism of particle formation. Ni⊂SiO2 nanocapsules were used as seeds to induce heterogeneous nucleation and subsequent growth within the nanocapsule via electroless nickel plating. Nickel nanoparticle growth occurs under high temperature alkaline

  10. [1+1+1] Cyclotrimerization for the Synthesis of Cyclopropanes.

    PubMed

    Manna, Srimanta; Antonchick, Andrey P

    2016-04-18

    The synthesis of small rings by functionalization of C(sp(3) )-H bonds remains a great challenge. We report for the first time a copper-catalyzed [1+1+1] cyclotrimerization of acetophenone derivatives under mild reaction conditions. The reaction has a broad scope for the stereoselective synthesis of cyclopropanes by trimerization of acetophenone. The developed transformation is based on an extraordinary copper-catalyzed cascade process that allows saturated carbocycles to be obtained for the first time by cyclotrimerization through functionalization of C(sp(3) )-H bonds. The cascade of sixfold C(sp(3) )-H bond functionalization allows the synthesis of cyclopropanes in a highly stereoselective approach. PMID:26997466

  11. Regio- and Stereoselective [2+2] Photodimerization of 3-Substituted 2-Alkoxy-2-oxo-2H-1,2-Benzoxaphosphorines

    SciTech Connect

    Nikolova, Rositca D.; Vayssilov, Georgi; Rodios, Nestor; Bojilova, Anka

    2002-05-31

    Diethyl 1,2-benzoxaphosphorine-3-carboxylates 5 undergo a regio- and stereoselective [2+2] photodimerization reaction in methanol solution under the action of sunlight, giving in all cases the corresponding anti head-to-tail dimers 6 and 7. Concerning the stereogenic P atom, the photodimerization is also stereoselective, and the centrosymmetric stereoisomer 6 predominates over the non symmetric P-epimer 7.

  12. Asymmetric Total Synthesis of Propindilactone G, Part 1: Initial Attempts towards the Synthesis of Schiartanes.

    PubMed

    Xu, Ling-Ming; You, Lin; Shan, Zhen-Hua; Yu, Ruo-Cheng; Zhang, Bo; Li, Yuan-He; Shi, Ying; Chen, Jia-Hua; Yang, Zhen

    2016-05-01

    Our first-generation synthetic study towards the total synthesis of propindilactone G (1) and its analogues is reported. The key synthetic steps were an intramolecular Pauson-Khand reaction (PKR) and a vinylogous Mukaiyama reaction (VMAR). The stereoselective synthesis of the CDE ring moiety with an all-carbon quaternary center through a PKR was difficult, whilst a VMAR afforded a product with the opposite stereochemistry at the C20 position on the side chain. These results led us to redesign our synthetic strategy for the total synthesis of compound 1. PMID:26991268

  13. A Green, Enantioselective Synthesis of Warfarin for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Wong, Terence C.; Sultana, Camille M.; Vosburg, David A.

    2010-01-01

    The enantioselective synthesis of drugs is of fundamental importance in the pharmaceutical industry. In this experiment, students synthesize either enantiomer of warfarin, a widely used anticoagulant, in a single step from inexpensive starting materials. Stereoselectivity is induced by a commercial organocatalyst, ("R","R")- or…

  14. Short Convergent Synthesis of the Mycolactone Core Through Lithiation-Borylation Homologations.

    PubMed

    Brown, Christopher A; Aggarwal, Varinder K

    2015-09-28

    Using iterative lithiation-borylation homologations, the mycolactone toxin core has been synthesized in 13 steps and 17% overall yield. The rapid build-up of molecular complexity, high convergence and high stereoselectivity are noteworthy features of this synthesis. PMID:26332797

  15. Asymmetric synthesis of Crispine A: constructing tetrahydroisoquinoline scaffolds using pummerer cyclizations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For the first time, a concise, linear and protecting group-free stereoselective synthesis of both enantiomers of crispine A have been achieved in six steps with an overall yield of less than or equal to 20%,starting from commercially available veratraldehyde. Asymmetric Keck allylation and trifluoro...

  16. Synthesis of highly enantio-enriched stereoisomers of hydroxy-GR24.

    PubMed

    Morris, J C; McErlean, C S P

    2016-01-28

    In contrast to a biomimetic electrophilic cyclisation cascade, we employ a contra-biomimetic nucleophilic cyclisation cascade to give the tricyclic core of 4-hydroxy-GR24 in a single step. Kinetic resolution using a stereoselective Noyori transfer hydrogenation enables the concise synthesis of any enantiomerically enriched 4-hydroxy-GR24 stereoisomer. PMID:26691225

  17. Alkene Dioxygenation with Malonoyl Peroxides: Synthesis of γ-Lactones, Isobenzofuranones, and Tetrahydrofurans.

    PubMed

    Alamillo-Ferrer, Carla; Karabourniotis-Sotti, Marianna; Kennedy, Alan R; Campbell, Matthew; Tomkinson, Nicholas C O

    2016-07-01

    Treatment of homoallylic alcohols or carboxylic acids with malonoyl peroxide 1 provides a stereoselective method for the preparation of tetrahydrofurans, γ-lactones, and isobenzofuranones in 44-82% yield and up to 27:1 trans selectivity. Application of this simple and effective heterocyclization in the synthesis of the antidepressant citalopram is also described. PMID:27314605

  18. Asymmetric synthesis of L-carbidopa based on a highly enantioselective α-amination.

    PubMed

    Pericas, Àlex; Shafir, Alexandr; Vallribera, Adelina

    2013-04-01

    A stereoselective synthesis of L-carbidopa in seven steps and 50% overall yield from commercial compounds is described. The key step involves a highly enantioselective α-amination reaction of an acyclic β-ketoester with di-tert-butyl azodicarboxylate induced by europium and (R,R)-diphenyl-pybox. PMID:23477289

  19. An efficient synthesis of N-substituted 3-nitrothiophen-2-amines.

    PubMed

    Vivek Kumar, Sundaravel; Muthusubramanian, Shanmugam; Menéndez, J Carlos; Perumal, Subbu

    2015-01-01

    A novel protocol for the synthesis of 3-nitro-N-aryl/alkylthiophen-2-amines in good yields from the reaction of α-nitroketene N,S-aryl/alkylaminoacetals and 1,4-dithiane-2,5-diol in the presence of K2CO3 in refluxing ethanol is described. This transformation generates two C-C bonds in a single operation and presumably proceeds through a reaction sequence comprising 2-mercaptoacetaldehyde generation, nucleophilic carbonyl addition, annelation and elimination steps. PMID:26664589

  20. A novel and efficient samarium iodide-mediated synthesis of neoflavonoids (4-arycloumarins)

    SciTech Connect

    Nagasawa, Kazuo; Ryohke, Hirosi; Ohnishi, Makoto; Ito, Keiichi

    1995-12-31

    Bioactive 4-arylcoumarins (4-aryl-2H-1-benzopyran-2-ones) have been recently isolated from the plants belonging to the families like Leguminosae, Guttiferae, and Compositae, some of which are still used as the traditional folk medicine. Despite many methods reported so far, there appears to be of limited success or of no success in some cases (II{sub b-g}) and, therefore, a simpler and more reliable one remains to be highly desired. Thus, a new and sterling protocol is now presented for the synthesis of neoflavonoids, which involves the intramolecular Reformatsky-type reaction via a one electron transfer process with samarium diiodide as a key step.

  1. An efficient synthesis of nanocrystalline MFI zeolite using different silica sources: A green approach

    SciTech Connect

    Kalita, Banani; Talukdar, Anup K.

    2009-02-04

    Nanocrystalline MFI zeolite was synthesized with a very broad range of silica to alumina ratios using an autoclave for periods of 7 h at 473 K under autogeneous pressure without seeding gel, promoter, organic solvent or sulfuric acid. The procedure has been successfully employed for the synthesis of MFI samples using fumed silica, colloidal silica, aerosil and tetraethylorthosilicate as silica sources. The synthesized samples were characterized by different techniques such as X-ray diffraction, Fourier transform infrared spectroscopy, Scanning electron microscopy. Their average crystallite size ranges from about 26 to 55 nm and they exhibit high crystallinity.

  2. A New and Efficient Approach to the Synthesis of Nicotine and Anabasine Analogues

    PubMed Central

    Huang, Kun; Ortiz-Marciales, Margarita; De Jesús, Melvin; Stepanenko, Viatcheslav

    2010-01-01

    A straightforward and practical approach was established for the synthesis of nicotine and anabasine analogues by the cyclization of mesylated 1-(3-pyridinyl)-1,4, and 1,5-diol derivatives to form the pyrrolidino or piperidino fragments. Nicotine analogue (S)-15 was prepared with good enantioselectivity using the developed azacyclization procedure of nonracemic (R)-1-pyridin-3-yl-butane-1,4-diol, which was obtained by the borane-mediated reduction of ketone 12 in the presence of the spiroborate ester derived from diphenyl prolinol and ethylene glycol. PMID:20161612

  3. Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N-Substituted 2-Oxazolones.

    PubMed

    He, Yun; Agarwal, Piyush K; Kiran, I N Chaithanya; Yu, Ruocheng; Cao, Bei; Zou, Cheng; Zhou, Xinghua; Xu, Huacheng; Xu, Biao; Zhu, Lei; Lan, Yu; Nicolaou, K C

    2016-06-01

    A mild and practical method for the construction of heterocycles from N-substituted 2-oxazolones through cascade, BF3 ⋅Et2 O/H2 O-catalyzed reactions involving iminium ion generation and trapping by external or internal olefinic and aryl moieties is described. Mechanistic and computational studies revealed the strong protic acid HBF4 as the initiating catalyst for these cascade reactions. Providing access to novel molecular diversity, these processes may facilitate chemical biology studies, drug discovery efforts and natural products synthesis. PMID:27113382

  4. An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

    PubMed Central

    Vivek Kumar, Sundaravel; Muthusubramanian, Shanmugam

    2015-01-01

    Summary A novel protocol for the synthesis of 3-nitro-N-aryl/alkylthiophen-2-amines in good yields from the reaction of α-nitroketene N,S-aryl/alkylaminoacetals and 1,4-dithiane-2,5-diol in the presence of K2CO3 in refluxing ethanol is described. This transformation generates two C–C bonds in a single operation and presumably proceeds through a reaction sequence comprising 2-mercaptoacetaldehyde generation, nucleophilic carbonyl addition, annelation and elimination steps. PMID:26664589

  5. One pot, rapid and efficient synthesis of water dispersible gold nanoparticles using alpha-amino acids

    NASA Astrophysics Data System (ADS)

    Wangoo, Nishima; Kaur, Sarabjit; Bajaj, Manish; Jain, D. V. S.; Sharma, Rohit K.

    2014-10-01

    A detailed study on the synthesis of spherical and monodispersed gold nanoparticles (AuNPs) using all of the 20 naturally occurring α-amino acids has been reported. The synthesized nanoparticles have been further characterized using various techniques such as absorbance spectroscopy, transmission electron microscopy, dynamic light scattering and nuclear magnetic resonance. Size control of the nanoparticles has been achieved by varying the ratio of the gold ion to the amino acid. These monodispersed water soluble AuNPs synthesized using non-toxic, naturally occurring α-amino acids as reducing and capping/stabilizing agents serve as a remarkable example of green chemistry.

  6. Hydroxamic acids in asymmetric synthesis.

    PubMed

    Li, Zhi; Yamamoto, Hisashi

    2013-02-19

    Metal-catalyzed stereoselective reactions are a central theme in organic chemistry research. In these reactions, the stereoselection is achieved predominantly by introducing chiral ligands at the metal catalyst's center. For decades, researchers have sought better chiral ligands for asymmetric catalysis and have made great progress. Nevertheless, to achieve optimal stereoselectivity and to catalyze new reactions, new chiral ligands are needed. Because of their high metal affinity, hydroxamic acids play major roles across a broad spectrum of fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first revealed their potential as chiral ligands for asymmetric synthesis in 1977: He published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective epoxidation of allylic alcohols before his discovery of Sharpless asymmetric epoxidation, which uses the titanium-tartrate complex as the chiral reagent. However, researchers have reported few highly enantioselective reactions using metal-hydroxamic acid as catalysts since then. This Account summarizes our research on metal-catalyzed asymmetric epoxidation using hydroxamic acids as chiral ligands. We designed and synthesized a series of new hydroxamic acids, most notably the C2-symmetric bis-hydroxamic acid (BHA) family. V-BHA-catalyzed epoxidation of allylic and homoallylic alcohols achieved higher activity and stereoselectivity than Sharpless asymmetric epoxidation in many cases. Changing the metal species led to a series of unprecedented asymmetric epoxidation reactions, such as (i) single olefins and sulfides with Mo-BHA, (ii) homoallylic and bishomoallylic alcohols with Zr- and Hf-BHA, and (iii) N-alkenyl sulfonamides and N-sulfonyl imines with Hf-BHA. These reactions produce uniquely functionalized chiral epoxides with good yields and enantioselectivities. PMID:23157425

  7. Hydroxamic Acids in Asymmetric Synthesis

    PubMed Central

    Li, Zhi; Yamamoto, Hisashi

    2012-01-01

    Metal-catalyzed stereoselective reactions are a central theme in organic chemistry research. In these reactions, the stereoselection is achieved predominantly by introducing chiral ligands at the metal catalyst’s center. For decades, researchers have sought better chiral ligands for asymmetric catalysis and have made great progress. Nevertheless, to achieve optimal stereoselectivity and to catalyze new reactions, new chiral ligands are needed. Due to their high metal affinity, hydroxamic acids play major roles across a broad spectrum of fields from biochemistry to metal extraction. Dr. K. Barry Sharpless first revealed their potential as chiral ligands for asymmetric synthesis in 1977: He published the chiral vanadium-hydroxamic-acid-catalyzed, enantioselective epoxidation of allylic alcohols before his discovery of Sharpless Asymmetric Epoxidation, which uses titanium-tartrate complex as the chiral reagent. However, researchers have reported few highly enantioselective reactions using metal-hydroxamic acid as catalysts since then. This Account summarizes our research on metal-catalyzed asymmetric epoxidation using hydroxamic acids as chiral ligands. We designed and synthesized a series of new hydroxamic acids, most notably the C2-symmetric bis-hydroxamic acid (BHA) family. V-BHA-catalyzed epoxidation of allylic and homoallylic alcohols achieved higher activity and stereoselectivity than Sharpless Asymmetric Epoxidation in many cases. Changing the metal species led to a series of unprecedented asymmetric epoxidation reactions, such as (i) single olefins and sulfides with Mo-BHA, (ii) homoallylic and bishomoallylic alcohols with Zr- and Hf-BHA, and (iii) N-alkenyl sulfonamides and N-sulfonyl imines with Hf-BHA. These reactions produce uniquely functionalized chiral epoxides with good yields and enantioselectivities. PMID:23157425

  8. Spray-combustion synthesis: efficient solution route to high-performance oxide transistors.

    PubMed

    Yu, Xinge; Smith, Jeremy; Zhou, Nanjia; Zeng, Li; Guo, Peijun; Xia, Yu; Alvarez, Ana; Aghion, Stefano; Lin, Hui; Yu, Junsheng; Chang, Robert P H; Bedzyk, Michael J; Ferragut, Rafael; Marks, Tobin J; Facchetti, Antonio

    2015-03-17

    Metal-oxide (MO) semiconductors have emerged as enabling materials for next generation thin-film electronics owing to their high carrier mobilities, even in the amorphous state, large-area uniformity, low cost, and optical transparency, which are applicable to flat-panel displays, flexible circuitry, and photovoltaic cells. Impressive progress in solution-processed MO electronics has been achieved using methodologies such as sol gel, deep-UV irradiation, preformed nanostructures, and combustion synthesis. Nevertheless, because of incomplete lattice condensation and film densification, high-quality solution-processed MO films having technologically relevant thicknesses achievable in a single step have yet to be shown. Here, we report a low-temperature, thickness-controlled coating process to create high-performance, solution-processed MO electronics: spray-combustion synthesis (SCS). We also report for the first time, to our knowledge, indium-gallium-zinc-oxide (IGZO) transistors having densification, nanoporosity, electron mobility, trap densities, bias stability, and film transport approaching those of sputtered films and compatible with conventional fabrication (FAB) operations. PMID:25733848

  9. Design and synthesis of efficient fluorescent dyes for incorporation into DNA backbone and biomolecule detection.

    PubMed

    Wang, Wei; Li, Alexander D Q

    2007-01-01

    We report here the design and synthesis of a series of pi-conjugated fluorescent dyes with D-A-D (D, donor; A, acceptor), D-pi-D, A-pi-A, and D-pi-A for applications as the signaling motif in biological-synthetic hybrid foldamers for DNA detection. The Horner-Wadsworth-Emmons (HWE) reaction and Knoevenagel condensation were demonstrated as the optimum ways for construction of long pi-conjugated systems. Such rodlike chromophores have distinct advantages, as their fluorescence properties are not quenched by the presence of DNA. To be incorporated into the backbone of DNA, the chromophores need to be reasonably soluble in organic solvent for solid-phase synthesis, and therefore a strategy of using flexible tetraethylene glycol (TEG) linkers at either end of these rodlike dyes was developed. The presence of TEG facilitates the protection of the chain-growing hydroxyl group with DMTrCl (dimethoxytrityl chloride) as well as the activation of the coupling step with phosphoramidite chemistry on an automated DNA synthesizer. To form fluorescence resonance energy transfer (FRET) pairs, six synthetic chromophores with blue to red fluorescence have been developed, and those with orthogonal fluorescent emission were chosen for incorporation into DNA-chromophore hybrid foldamers. PMID:17508711

  10. Spray-combustion synthesis: Efficient solution route to high-performance oxide transistors

    PubMed Central

    Yu, Xinge; Smith, Jeremy; Zhou, Nanjia; Zeng, Li; Guo, Peijun; Xia, Yu; Alvarez, Ana; Aghion, Stefano; Lin, Hui; Yu, Junsheng; Chang, Robert P. H.; Bedzyk, Michael J.; Ferragut, Rafael; Marks, Tobin J.; Facchetti, Antonio

    2015-01-01

    Metal-oxide (MO) semiconductors have emerged as enabling materials for next generation thin-film electronics owing to their high carrier mobilities, even in the amorphous state, large-area uniformity, low cost, and optical transparency, which are applicable to flat-panel displays, flexible circuitry, and photovoltaic cells. Impressive progress in solution-processed MO electronics has been achieved using methodologies such as sol gel, deep-UV irradiation, preformed nanostructures, and combustion synthesis. Nevertheless, because of incomplete lattice condensation and film densification, high-quality solution-processed MO films having technologically relevant thicknesses achievable in a single step have yet to be shown. Here, we report a low-temperature, thickness-controlled coating process to create high-performance, solution-processed MO electronics: spray-combustion synthesis (SCS). We also report for the first time, to our knowledge, indium-gallium-zinc-oxide (IGZO) transistors having densification, nanoporosity, electron mobility, trap densities, bias stability, and film transport approaching those of sputtered films and compatible with conventional fabrication (FAB) operations. PMID:25733848

  11. Simple, efficient protocol for enzymatic synthesis of uniformly 13C, 15N-labeled DNA for heteronuclear NMR studies.

    PubMed Central

    Masse, J E; Bortmann, P; Dieckmann, T; Feigon, J

    1998-01-01

    The use of uniformly 13C,15N-labeled RNA has greatly facilitated structural studies of RNA oligonucleotides by NMR. Application of similar methodologies for the study of DNA has been limited, primarily due to the lack of adequate methods for sample preparation. Methods for both chemical and enzymatic synthesis of DNA oligonucleotides uniformly labeled with 13C and/or 15N have been published, but have not yet been widely used. We have developed a modified procedure for preparing uniformly 13C,15N-labeled DNA based on enzymatic synthesis using Taq DNA polymerase. The highly efficient protocol results in quantitative polymerization of the template and approximately 80% incorporation of the labeled dNTPs. Procedures for avoiding non-templated addition of nucleotides or for their removal are given. The method has been used to synthesize several DNA oligonucleotides, including two complementary 15 base strands, a 32 base DNA oligonucleotide that folds to form an intramolecular triplex and a 12 base oligonucleotide that dimerizes and folds to form a quadruplex. Heteronuclear NMR spectra of the samples illustrate the quality of the labeled DNA obtained by these procedures. PMID:9592146

  12. Efficient synthesis of ammonia from N2 and H2 alone in a ferroelectric packed-bed DBD reactor

    NASA Astrophysics Data System (ADS)

    Gómez-Ramírez, A.; Cotrino, J.; Lambert, R. M.; González-Elipe, A. R.

    2015-12-01

    A detailed study of ammonia synthesis from hydrogen and nitrogen in a planar dielectric barrier discharge (DBD) reactor was carried out. Electrical parameters were systematically varied, including applied voltage and frequency, electrode gap, and type of ferroelectric material (BaTiO3 versus PZT). For selected operating conditions, power consumption and plasma electron density were estimated from Lissajous diagrams and by application of the Bolsig  +  model, respectively. Optical emission spectroscopy was used to follow the evolution of plasma species (\\text{N}{{\\text{H}}*},{{\\text{N}}*},~{N}2+~\\text{and} ~{N}2* ) as a function of applied voltage with both types of ferroelectric material. PZT gave both greater energy efficiency and higher ammonia yield than BaTiO3: 0.9 g NH3 kWh-1 and 2.7% single pass N2 conversion, respectively. This performance is substantially superior to previously published findings on DBD synthesis of NH3 from N2 and H2 alone. The influence of electrical working parameters, the beneficial effect of PZT and the importance of controlling reactant residence time are rationalized in a reaction model that takes account of the principal process variables

  13. Highly efficient enzymatic synthesis of an ascorbyl unstaturated fatty acid ester with ecofriendly biomass-derived 2-methyltetrahydrofuran as cosolvent.

    PubMed

    Hu, Ying-Dan; Qin, Ye-Zhi; Li, Ning; Zong, Min-Hua

    2014-01-01

    Enzymatic synthesis of ascorbyl undecylenate, an unsaturated fatty acid ester of ascorbic acid, was reported with biomass-derived 2-methyltetrahydrofuran (MeTHF) as the cosolvent. Of the immobilized lipases tested, Candida antarctica lipase B (CAL-B) showed the highest activity for enzymatic synthesis of ascorbyl undecylenate. Effect of reaction media on the enzymatic reaction was studied. The cosolvent mixture, t-butanol-MeTHF (1:4, v/v) proved to be the optimal medium, in which not only ascorbic acid had moderate solubility, but also CAL-B showed a high activity, thus addressing the major problem of the solvent conflict for dissolving substrate and keeping satisfactory enzyme activity. In addition, the enzyme was much more stable in MeTHF and t-butanol-MeTHF (1:4) than in previously widely used organic solvents, t-butanol, 2-methyl-2-butanol, and acetone. The much higher initial reaction rate in this cosolvent mixture may be rationalized by the much lower apparent activation energy of this enzymatic reaction (26.6 vs. 38.1-39.1 kJ/mol) and higher enzyme catalytic efficiency (Vmax /Km , 8.4 vs. 1.3-1.4 h(-1) ). Ascorbyl undecylenate was obtained with the yields of 84-89% and 6-regioselectivity of >99% in t-butanol-MeTHF (1:4) at supersaturated substrate concentrations (60 and 100 mM) after 5-8 h. PMID:24891225

  14. Synthesis of amino-rich silica-coated magnetic nanoparticles for the efficient capture of DNA for PCR.

    PubMed

    Bai, Yalong; Cui, Yan; Paoli, George C; Shi, Chunlei; Wang, Dapeng; Zhou, Min; Zhang, Lida; Shi, Xianming

    2016-09-01

    Magnetic separation has great advantages over traditional bio-separation methods and has become popular in the development of methods for the detection of bacterial pathogens, viruses, and transgenic crops. Functionalization of magnetic nanoparticles is a key factor for efficient capture of the target analytes. In this paper, we report the synthesis of amino-rich silica-coated magnetic nanoparticles using a one-pot method. This type of magnetic nanoparticle has a rough surface and a higher density of amino groups than the nanoparticles prepared by a post-modification method. Furthermore, the results of hydrochloric acid treatment indicated that the magnetic nanoparticles were stably coated. The developed amino-rich silica-coated magnetic nanoparticles were used to directly adsorb DNA. After magnetic separation and blocking, the magnetic nanoparticles and DNA complexes were used directly for the polymerase chain reaction (PCR), without onerous and time-consuming purification and elution steps. The results of real-time quantitative PCR showed that the nanoparticles with higher amino group density resulted in improved DNA capture efficiency. The results suggest that amino-rich silica-coated magnetic nanoparticles are of great potential for efficient bio-separation of DNA prior to detection by PCR. PMID:27187190

  15. Efficient utilization of greenhouse gases in a gas-to-liquids process combined with CO2/steam-mixed reforming and Fe-based Fischer-Tropsch synthesis.

    PubMed

    Zhang, Chundong; Jun, Ki-Won; Ha, Kyoung-Su; Lee, Yun-Jo; Kang, Seok Chang

    2014-07-15

    Two process models for carbon dioxide utilized gas-to-liquids (GTL) process (CUGP) mainly producing light olefins and Fischer-Tropsch (F-T) synthetic oils were developed by Aspen Plus software. Both models are mainly composed of a reforming unit, an F-T synthesis unit and a recycle unit, while the main difference is the feeding point of fresh CO2. In the reforming unit, CO2 reforming and steam reforming of methane are combined together to produce syngas in flexible composition. Meanwhile, CO2 hydrogenation is conducted via reverse water gas shift on the Fe-based catalysts in the F-T synthesis unit to produce hydrocarbons. After F-T synthesis, the unreacted syngas is recycled to F-T synthesis and reforming units to enhance process efficiency. From the simulation results, it was found that the carbon efficiencies of both CUGP options were successfully improved, and total CO2 emissions were significantly reduced, compared with the conventional GTL processes. The process efficiency was sensitive to recycle ratio and more recycle seemed to be beneficial for improving process efficiency and reducing CO2 emission. However, the process efficiency was rather insensitive to split ratio (recycle to reforming unit/total recycle), and the optimum split ratio was determined to be zero. PMID:24933030

  16. Efficient and Stereocontrolled Synthesis of 1,2,4-Trioxolanes Useful for Ferrous Iron-Dependent Drug Delivery

    PubMed Central

    2015-01-01

    Ferrous iron-promoted reduction of a hindered peroxide bond underlies the antimalarial action of the 1,2,4-trioxane artemisinin and the 1,2,4-trioxolane arterolane. In appropriately designed systems, a 1,2,4-trioxolane ring can serve as a trigger to realize ferrous iron-dependent and parasite-selective drug delivery, both in vitro and in vivo. A stereocontrolled, expeditious (three steps), and efficient (67–71% overall yield) synthesis of 1,2,4-trioxolanes possessing the requisite 3″ substitution pattern that enables ferrous iron-dependent drug delivery is reported. The key synthetic step involves a diastereoselective Griesbaum co-ozonolysis reaction to afford primarily products with a trans relationship between the 3″ substituent and the peroxide bridge, as confirmed by X-ray structural analysis of a 3″-substituted 4-nitrobenzoate analogue. PMID:25331549

  17. Efficient and stereocontrolled synthesis of 1,2,4-trioxolanes useful for ferrous iron-dependent drug delivery.

    PubMed

    Fontaine, Shaun D; DiPasquale, Antonio G; Renslo, Adam R

    2014-11-01

    Ferrous iron-promoted reduction of a hindered peroxide bond underlies the antimalarial action of the 1,2,4-trioxane artemisinin and the 1,2,4-trioxolane arterolane. In appropriately designed systems, a 1,2,4-trioxolane ring can serve as a trigger to realize ferrous iron-dependent and parasite-selective drug delivery, both in vitro and in vivo. A stereocontrolled, expeditious (three steps), and efficient (67-71% overall yield) synthesis of 1,2,4-trioxolanes possessing the requisite 3″ substitution pattern that enables ferrous iron-dependent drug delivery is reported. The key synthetic step involves a diastereoselective Griesbaum co-ozonolysis reaction to afford primarily products with a trans relationship between the 3″ substituent and the peroxide bridge, as confirmed by X-ray structural analysis of a 3″-substituted 4-nitrobenzoate analogue. PMID:25331549

  18. Facile and efficient one-pot synthesis of 2-arylbenzoxazoles using hydrogen tetrachloroaurate as catalyst under oxygen atmosphere*

    PubMed Central

    Liu, Yun-kui; Mao, Da-jie; Lou, Shao-jie; Qian, Jian-qiang; Xu, Zhen-yuan

    2009-01-01

    In this paper, we presented a novel method for the facile and efficient one-pot synthesis of 2-arylbenzoxazoles, which were directly synthesized from 2-aminophenol and aldehydes catalyzed by hydrogen tetrachloroaurate (HAuCl4·4H2O) under an oxygen atmosphere with anhydrous tetrahydrofuran (THF) as solvent or in solvent-free condition. The results show that this method could bring excellent yields as high as 96%. THF was proven to be the best choice among several solvents screened and the reaction was tolerated with a variety of aromatic aldehydes possessing electron-donating or withdrawing groups. The advantages of the present method lie in catalytic process using economic and environmentally benign dioxygen as oxidant. PMID:19489113

  19. Modular solid-phase synthesis, catalytic application and efficient recycling of supported phosphine-phosphite ligand libraries.

    PubMed

    Heutz, Frank J L; Kamer, Paul C J

    2016-02-01

    In spite of decades of research in the field of homogeneous asymmetric catalysis the discovery of new high performance catalysts still relies heavily on trial-and-error. There is still a lack of efficient combinatorial methods which enable the synthesis and screening of vast ligand libraries, especially for bidentate phosphorus ligands. Here we present a highly modular solid-phase synthetic approach which provides facile access to libraries of phosphine-phosphite ligands in quantitative yield requiring only minimal work-up. The obtained library of supported phosphine-phosphites was successfully applied in rhodium catalyzed asymmetric hydrogenation obtaining high enantioselectivities up to 98%. Also, these polymer supported ligands could be successfully recycled under batch conditions exhibiting only a small decline of activity and no loss of selectivity. PMID:26486695

  20. Synthesis of the aggregation pheromone of the Colorado potato beetle from its degradation product.

    PubMed

    Wacławczyk-Biedroń, Weronika; Frąckowiak-Wojtasek, Bożena; Strub, Daniel; Rzechak, Magdalena; Wojtasek, Hubert

    2015-09-01

    Incubation of the Colorado potato beetle aggregation pheromone, (S)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one, with antennal or leg extracts from this beetle gave 6-methyl-5-hepten-2-one as the major product. This ketone was used as a substrate in a stereoselective synthesis of the pheromone. It was attached to the butanediacetal of glycolic acid with good stereoselectivity and the desired isomer was further enriched by purification of the product of this reaction on silica gel. PMID:26169127

  1. Origins of stereoselectivity in intramolecular aldol reactions catalyzed by cinchona amines.

    PubMed

    Lam, Yu-Hong; Houk, K N

    2015-02-11

    The intramolecular aldol condensation of 4-substituted heptane-2,6-diones leads to chiral cyclohexenones. The origins of the enantioselectivities of this reaction, disclosed by List et al. using a cinchona alkaloid-derived primary amine (cinchona amine) organocatalyst, have been determined with dispersion-corrected density functional theory (DFT). The stereocontrol hinges on the chair preference of the substrate-enamine intermediate and the conformational preferences of a hydrogen-bonded nine-membered aldol transition state containing eight heavy atoms. The conformations of the hydrogen-bonded ring in the various stereoisomeric transition structures have been analyzed in detail and shown to closely resemble the conformers of cyclooctane. A model of stereoselectivity is proposed for the cinchona amine catalysis of this reaction. The inclusion of Grimme's dispersion corrections in the DFT calculations (B3LYP-D3(BJ)) substantially improves the agreement of the computed energetics and experiment, attesting to the importance of dispersion effects in stereoselectivity. PMID:25629689

  2. Stereoselective bimolecular phenoxyl radical coupling by an auxiliary (dirigent) protein without an active center

    SciTech Connect

    Davin, L.B.; Wang, Huai-Bin; Crowell, A.L.

    1997-01-17

    The regio- and stereospecificity of bimolecular phenoxy radical coupling reactions, of especial importance in lignin and lignan biosynthesis, are clearly controlled in some manner in vivo; yet in vitro coupling by oxidases, such as laccases, only produce racemic products. In other words, laccases, peroxidases, and comparable oxidases are unable to control regio- or stereospecificity by themselves and thus some other agent must exist. A 78-kilodalton protein has been isolated that, in the presence of an oxidase or one electron oxidant, effects stereoselective bimolecular phenoxy radical coupling in vitro. Itself lacking a catalytically active (oxidative) center, its mechanism of action is presumed to involve capture of E-coniferyl alcohol-derived free-radical intermediates, with consequent stereoselective coupling to give (+)-pinoresinol. 25 refs., 6 figs., 3 tabs.

  3. Efficient Synthesis of Cyclic Block Copolymers by Rotaxane Protocol by Linear/Cyclic Topology Transformation.

    PubMed

    Valentina, Stephanie; Ogawa, Takahiro; Nakazono, Kazuko; Aoki, Daisuke; Takata, Toshikazu

    2016-06-20

    High-yielding synthesis of cyclic block copolymer (CBC) using the rotaxane protocol by linear-cyclic polymer topology transformation was first demonstrated. Initial complexation of OH-terminated sec-ammonium salt and a crown ether was followed by the successive living ring-opening polymerizations of two lactones to a linear block copolymer having a rotaxane structure by the final capping of the propagation end. CBC was obtained in a high yield by an exploitation of the mechanical linkage through the translational movement of the rotaxane component to transform polymer structure from linear to cyclic. Furthermore, the change of the polymer topology was translated into a macroscopic change in crystallinity of the block copolymer. PMID:27037975

  4. Synthesis of homogeneous Pt-bimetallic nanoparticles as highly efficient electrocatalysts.

    SciTech Connect

    Wang, C.; Chi, M.; Li, D.; van der Vliet, D.; Wang, G.; Lin, Q.; Mitchell, J.; More, K. L.; Markovic, N. M.; Stamenkovic, V. R.

    2011-01-01

    Alloying has shown enormous potential for tailoring the atomic and electronic structures, and improving the performance of catalytic materials. Systematic studies of alloy catalysts are, however, often compromised by inhomogeneous distribution of alloying components. Here we introduce a general approach for the synthesis of monodispersed and highly homogeneous Pt-bimetallic alloy nanocatalysts. Pt{sub 3}M (where M = Fe, Ni, or Co) nanoparticles were prepared by an organic solvothermal method and then supported on high surface area carbon. These catalysts attained a homogeneous distribution of elements, as demonstrated by atomic-scale elemental analysis using scanning transmission electron microscopy. They also exhibited high catalytic activities for the oxygen reduction reaction (ORR), with improvement factors of 2-3 versus conventional Pt/carbon catalysts. The measured ORR catalytic activities for Pt{sub 3}M nanocatalysts validated the volcano curve established on extended surfaces, with Pt{sub 3}Co being the most active alloy.

  5. Synthesis of taurine-fluorescein conjugate and evaluation of its retina-targeted efficiency in vitro.

    PubMed

    Huang, Meihong; Song, Jiaqi; Lu, Bingzheng; Huang, Huizhi; Chen, Yizhen; Yin, Wei; Zhu, Wenbo; Su, Xinwen; Wu, Chuanbin; Hu, Haiyan

    2014-12-01

    In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F-Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F-Tau. The cellular uptake of F-Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F-Tau compared with fluorescein. As compared with fluorescein, F-Tau showed little toxicity, and was retained longer by cells in uptake experiments. F-Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina. PMID:26579416

  6. Structural Determinants for the Stereoselective Hydrolysis of Chiral Substrates by Phosphotriesterase

    SciTech Connect

    Tsai, P.; Fan, Y; Kim, J; Yang, L; Almo, S; Gao, Y; Raushel, F

    2010-01-01

    Wild-type phosphotriesterase (PTE) preferentially hydrolyzes the R{sub P} enantiomers of the nerve agents sarin (GB) and cyclosarin (GF) and their chromophoric analogues. The active site of PTE can be subdivided into three binding pockets that have been denoted as the small, large, and leaving group pockets based on high-resolution crystal structures. The sizes and shapes of these pockets dictate the substrate specificity and stereoselectivity for catalysis. Mutants of PTE that exhibit substantial changes in substrate specificity and the ability to differentiate between chiral substrates have been prepared. For example, the G60A mutant is stereoselective for the hydrolysis of the R{sub P} enantiomer of the chromophoric analogues of sarin and cyclosarin, whereas the H254G/H257W/L303T (GWT) mutant reverses the stereoselectivity for the enantiomers of these two compounds. Molecular dynamics simulations and high-resolution X-ray structures identified the correlations between structural changes in the active site and the experimentally determined kinetic parameters for substrate hydrolysis. New high-resolution structures were determined for the H257Y/L303T (YT), I106G/F132G/H257Y (GGY), and H254Q/H257F (QF) mutants of PTE. Molecular dynamics calculations were conducted using the SP and RP enantiomers of the analogues for sarin and cyclosarin for the wild-type PTE and the G60A, YT, GGY, QF, and GWT mutants. The experimental stereoselectivity correlated nicely with the difference in the computed angle of attack for the nucleophilic hydroxide relative to the phenolic leaving group of the substrate.

  7. Stereoselective sulfate conjugation of racemic 4-hydroxypropranolol by human and rat liver cytosol

    SciTech Connect

    Walle, T.; Walle, U.K. )

    1991-03-01

    The objective of this study was to determine the stereochemistry of sulfoconjugation of a chiral phenolic amine drug, 4-hydroxypropranolol (HOP), by the human liver. The reaction was catalyzed by the 100,000 g cytosol as the phenolsulfotransferase (PST) enzyme source with PAP35S as the co-substrate. The enantiomers of the intact sulfate conjugate formed, (+)-HOP35S and (-)-HOP35S, were separated by HPLC and measured by liquid scintillation spectrometry. Complex velocity vs. substrate concentration curves were obtained with two peaks of activity, one at 3 microM (high affinity) and one at 500 microM (low affinity). The high-affinity reaction demonstrated a high degree of stereoselectivity. Whereas the affinity of the enantiomers for this reaction was identical, with a very low apparent KM value of 0.59 microM, the apparent Vmax value for (+)-HOPS formation was 4.6-fold higher than for (-)-HOPS. In sharp contrast, the low-affinity reaction, with an apparent KM of 65 microM, was not stereoselective. Inhibition of the high-affinity reaction by elevated temperature, but not by dichloronitrophenol, indicated that this activity was due to a monoamine form of PST. Inhibition of the low-affinity reaction by dichloronitrophenol, but not by elevated temperature, indicated that this activity was due to a phenol form of PST. As a comparison, experiments with the rat liver cytosol demonstrated only one activity, with apparent KM values of 50 microM for both enantiomers and opposite stereoselectivity in maximum velocity compared to humans, {plus minus}-HOPS ratio 0.72. The results of this study demonstrate stereoselectivity in human hepatic sulfation of a chiral phenolic amine, with clear differences between PST isoenzymes.

  8. Regio- and stereoselectivity of P450-catalysed hydroxylation of steroids controlled by laboratory evolution

    NASA Astrophysics Data System (ADS)

    Kille, Sabrina; Zilly, Felipe E.; Acevedo, Juan P.; Reetz, Manfred T.

    2011-09-01

    A current challenge in synthetic organic chemistry is the development of methods that allow the regio- and stereoselective oxidative C-H activation of natural or synthetic compounds with formation of the corresponding alcohols. Cytochrome P450 enzymes enable C-H activation at non-activated positions, but the simultaneous control of both regio- and stereoselectivity is problematic. Here, we demonstrate that directed evolution using iterative saturation mutagenesis provides a means to solve synthetic problems of this kind. Using P450 BM3(F87A) as the starting enzyme and testosterone as the substrate, which results in a 1:1 mixture of the 2β- and 15β-alcohols, mutants were obtained that are 96-97% selective for either of the two regioisomers, each with complete diastereoselectivity. The mutants can be used for selective oxidative hydroxylation of other steroids without performing additional mutagenesis experiments. Molecular dynamics simulations and docking experiments shed light on the origin of regio- and stereoselectivity.

  9. Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids

    SciTech Connect

    Freneaux, E.; Fromenty, B.; Berson, A.; Labbe, G.; Degott, C.; Letteron, P.; Larrey, D.; Pessayre, D. , Hopital Beaujon, Clichy )

    1990-11-01

    The effects of the R-(-) and S-(+)ibuprofen enantiomers were first studied in vitro with mouse liver mitochondria incubated in the presence of various concentrations of exogenous coenzyme A. In the presence of a low concentration of coenzyme A (2.5 microM), the R-(-)enantiomer (which forms an acylcoenzyme A) inhibited stereoselectively the beta oxidation of (1-{sup 14}C)palmitic acid but not that of (1-{sup 14}C)palmitoyl-L-carnitine (which can directly enter the mitochondria). In the presence, however, of a concentration of coenzyme A (50 microM) reproducing that present in liver cell cytosol, both enantiomers (2 mM) slightly inhibited the beta oxidation of (1-{sup 14}C)palmitic acid and markedly inhibited the beta oxidation of (1-{sup 14}C)octanoic acid and (1-{sup 14}C)butyric acid. In vivo, both enantiomers (1 mmol.kg-1) similarly inhibited the formation of ({sup 14}C)CO{sub 2} from (1-{sup 14}C)fatty acids. Both enantiomers similarly decreased plasma ketone bodies. Both similarly increased hepatic triglycerides, and both produced mild microvesicular steatosis of the liver. We conclude that both ibuprofen enantiomers inhibit beta oxidation of fatty acids in vitro and in vivo. In addition, the R-(-)enantiomer may stereoselectively sequester coenzyme A; at low concentrations of coenzyme A in vitro, this may stereoselectively inhibit the mitochondrial uptake and beta oxidation of long chain fatty acids.

  10. Asymmetric Total Synthesis of (+)-Ryanodol and (+)-Ryanodine.

    PubMed

    Masuda, Kengo; Koshimizu, Masaki; Nagatomo, Masanori; Inoue, Masayuki

    2016-01-01

    (+)-Ryanodine (1) is the ester derivative of 1H-pyrrole-2-carboxylic acid and the complex terpenoid (+)-ryanodol (2), which possesses eleven contiguous stereogenic centers on the ABCDE-ring system. Compound 1 is known to be a potent modulator of intracellular calcium release channels, whereas the activity of 2 is significantly weaker. To chemically construct 1, the multiple oxygen functional groups must be installed on the fused pentacycle in stereoselective fashions and the extremely hindered C3-hydroxy group must be acylated in a site-selective manner. First, the total synthesis of 2 was accomplished by introducing the five stereocenters from the previously prepared enantiopure ABDE-ring 7. Stereoselective construction of the C3-secondary, C2- and C6-tertiary alcohols was achieved by three nucleophilic reactions. The C9- and C10-trisubstituted carbon centers were regio- and stereoselectively introduced by hydroboration/oxidation of the six-membered C-ring, which was formed by the ring-closing metathesis reaction. Direct esterification of the C3-alcohol with pyrrole-2-carboxylic acid proved unsuccessful; therefore, we developed a new, two-step protocol for attachment of the pyrrole moiety. The C3-hydroxy group was first converted into the less sterically cumbersome glycine ester, which was then transformed into the pyrrole ring through condensation with 1,3-bis(dimethylamino)allylium tetrafluoroborate. This procedure resulted in the first total synthesis of 1. PMID:26616265

  11. Total Synthesis of (+)-SCH 351448: Efficiency via Chemoselectivity and Redox-Economy Powered by Metal Catalysis.

    PubMed

    Wang, Gang; Krische, Michael J

    2016-07-01

    The polyketide natural product (+)-SCH 351448, a macrodiolide ionophore bearing 14 stereogenic centers, is prepared in 14 steps (LLS). In eight prior syntheses, 22-32 steps were required. Multiple chemoselective and redox-economic functional group interconversions collectively contribute to a step-change in efficiency. PMID:27337561

  12. Efficient utilization of crude glycerol as fermentation substrate in the synthesis of poly(3-hydroxybutyrate) biopolymers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One refined and 2 crude glycerol samples were utilized to produce poly(3-hydroxybutyrate) (PHB) by Pseudomonas oleovorans NRRL B-14682. Fermentation conditions were determined to efficiently utilize glycerol while maintaining PHB yields. A batch culture protocol including 1% glycerol and an aerati...

  13. Efficient aziridine synthesis in metastable crystalline phases by photoinduced denitrogenation of crystalline triazolines.

    PubMed

    de Loera, Denisse; Garcia-Garibay, Miguel A

    2012-08-01

    The solid-state photodenitrogenation of crystalline triazolines proceeds with high efficiency to form the corresponding aziridines in high chemical yields upon selection of the proper irradiation wavelength. It was shown that the solid-to-solid reactions occur by formation of the product in metastable crystalline phases. PMID:22794188

  14. Highly efficient and versatile synthesis of lactams and N-heterocycles via Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reactions.

    PubMed

    Qi, Jianguo; Sun, Chenbin; Tian, Yulin; Wang, Xiaojian; Li, Gang; Xiao, Qiong; Yin, Dali

    2014-01-01

    The discovery and development of an efficient and versatile method for the synthesis of N-substituted lactams is described. Pyrrolindinones, piperidones, and structurally related heterocycles were formed by Al(OTf)3-catalyzed cascade cyclization and ionic hydrogenation reactions of corresponding nitrogen substituted ketoamides in good yields. PMID:24313882

  15. Microwave-assisted stereoselective approach to novel steroidal ring D-fused 2-pyrazolines and an evaluation of their cell-growth inhibitory effects in vitro.

    PubMed

    Mótyán, Gergő; Kovács, Ferenc; Wölfling, János; Gyovai, András; Zupkó, István; Frank, Éva

    2016-08-01

    Novel ring D-condensed 2-pyrazolines in the Δ(5)-androstene series were efficiently synthesized from 16-dehydropregnenolone or its acetate with different arylhydrazines or methylhydrazine, respectively, under microwave irradiation. The reactions are assumed to occur via hydrazone intermediates, followed by intramolecular 1,4-addition leading to the fused heteroring stereoselectively with a 16α,17α-cis ring junction. The synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative activities against four human breast (MCF7, T47D, MDA-MB-231 and MDA-MB-361) and three cervical (HeLa, C33A and SiHA) malignant cell lines. Flow cytometry revealed that the most potent agent elicited a cell cycle disturbance. PMID:27154752

  16. The Catalytic Enantioselective Total Synthesis of (+)-Liphagal**

    PubMed Central

    Day, Joshua J.; McFadden, Ryan M.; Virgil, Scott C.; Kolding, Helene; Alleva, Jennifer L.; Stoltz, Brian M.

    2012-01-01

    Ring a ding: The first catalytic enantioselective total synthesis of the meroterpenoid natural product (+)-liphagal is disclosed. The approach showcases a variety of technology including enantioselective enolate alkylation, a photochemical alkyne-alkene [2+2] reaction, microwave-assisted metal catalysis, and an intramolecular aryne capture cyclization reaction. Pivotal to the successful completion of the synthesis was a sequence involving ring expansion from a [6-5-4] tricycle to a [6-7] bicyclic core followed by stereoselective hydrogenation of a sterically occluded tri-substituted olefin to establish the trans homodecalin system found in the natural product. PMID:21671325

  17. Facile and Efficient Synthesis of Bismuth Nanowires for Improved Photocatalytic Activity.

    PubMed

    Li, Yawen; Zhao, Yan; Wu, Gongjuan; Zhao, Jingzhe

    2016-05-16

    An aqueous reduction method was reported for the synthesis of bismuth nanowires (Bi NWs) 5-10 nm in diameter and several micrometers in length under the guidance of PVP molecules. The reactions were performed at 80 °C by reducing bismuth chloride with sodium hypophosphite first in acid and then under neutral circumstances. The key to successful preparation of the Bi NWs is regulation of the reduction speed by control of the pH value. The morphology evolution of the samples was also found to have a strong dependence on the reaction parameters, including the introduction amount and molecular weight of PVP molecules. A solid-solution-solid (SSS) mechanism was proposed for the nucleation and growth of Bi NWs in our strategy. The as-prepared Bi NWs exhibit excellent visible-light photocatalytic activities for the degradation of the organic pollutant Rhodamine B (RhB) and colorless bisphenol A (BPA). The good recyclability of the Bi NWs on RhB photodegradation demonstrates the possibility of their practical applications. PMID:27145289

  18. Efficient synthesis of pure monotosylated beta-cyclodextrin and its dimers.

    PubMed

    Tripodo, Giuseppe; Wischke, Christian; Neffe, Axel T; Lendlein, Andreas

    2013-11-15

    6-O-Monotosyl-β-cyclodextrin (mono-Ts-βCD) is one of the most important intermediates in the production of substituted βCD. So far, performing the monotosylation reaction and, in particular, the purification steps was challenging, relied on toxic solvents, and resulted in long and expensive procedures at, importantly, low yields. Here, the reaction of cyclodextrin with p-toluenesulfonyl chloride in aqueous environment is described to obtain a highly pure mono-Ts-βCD, for which a single-step purification with a cation exchange resin was applied. With this synthetic route and purification, yields could be increased from typically <10-15% to 35%, and organic solvents could be avoided. As characterized by FTIR, mass spectrometry, elemental analysis, and NMR, mono-Ts-βCD was obtained with a molar purity of >98mol%. From mono-Ts-βCD, β-cyclodextrin dimers linked by ethylenediamine (bis-Et-βCD) were successfully prepared (yield 93%, purity 96mol%) in a one-step approach using an anion exchange resin to trap leaving groups that typically interfere in the reaction. This synthesis procedure with a direct collection of side-products may be a general strategy applicable for nucleophilic substitution of tosylated cyclodextrins. PMID:24060538

  19. Efficient synthesis of core@shell Fe3O4@Au nanoparticles

    NASA Astrophysics Data System (ADS)

    Alonso-Cristobal, Paulino; Laurenti, Marco; Lopez-Cabarcos, Enrique; Rubio-Retama, Jorge

    2015-07-01

    The synthesis of Fe3O4@Au nanoparticles has received much attention due to promising applications in the biomedical field. In this work, we produced Fe3O4@Au nanoparticles by using a two-step solvothermal route that employed Fe3O4 nanoparticles as seeds for the Au deposition. Although this protocol leads to highly monodisperse and reproducible Fe3O4@Au nanoparticles it was necessary to perform a systematic study to have a better understanding, improve the yield and allow us to obtain a tunable result. We demonstrated that the Au:Fe3O4 ratio is a key parameter that, contrary to what could be expected, does not influence the Au shell thickness. However, this parameter should be optimized because it strongly influences the yield. When the Au:Fe3O4 ratio was low there were plenty of uncoated Fe3O4 nanoparticles, whereas when the Au:Fe3O4 ratio was high there could be some pure Au nanoparticles together with the desired Fe3O4@Au nanoparticles. Furthermore we demonstrated that the Au shell thickness can be tuned by varying the reaction temperature. This paper describes the influence of both parameters and proposes a mechanism of the synthetic process by studying parametrically the morphological and structural evolution of the nanoparticles by TEM, DLS, SQUID and UV-vis spectroscopy.

  20. Facile mesoporous template-assisted hydrothermal synthesis of ordered mesoporous magnesium silicate as an efficient adsorbent

    NASA Astrophysics Data System (ADS)

    Lu, Qingshan; Li, Qiang; Zhang, Jingjing; Li, Jingfeng; Lu, Jinhua

    2016-01-01

    Mesoporous materials with unique structure as well as special morphology have potential applications in pollutant adsorption. In this work, using mesoporous silica SBA-15 filled with carbon (C@SBA-15) as both silicon source and assisted template, the ordered mesoporous magnesium silicate (Mg3Si4O9(OH)4) has been fabricated at 140 °C by a novel and facile hydrothermal method. During the hydrothermal process, the magnesium silicate grew along the silica walls at the expense of consuming silica and deposited on the carbon surface of the C@SBA-15. Meanwhile, the rigid carbon inside the pores of the SBA-15 supported the magnesium silicate as mesoporous walls under hydrothermal condition. The obtained magnesium silicate possessed ordered mesoporous structure, high specific surface area of 446 m2/g, large pore volume of 0.84 cm3/g, and hierarchical structure assembled with ultrathin nanosheets of 15 nm in thickness. These characteristics endow the ordered mesoporous magnesium silicate with the fast adsorption rate and high adsorption capacity of 382 mg/g for methylene blue. In addition, this synthesis method opens a new approach to fabricate other ordered mesoporous silicates.

  1. Efficient MW-Assisted Synthesis, Spectroscopic Characterization, X-ray and Antioxidant Properties of Indazole Derivatives.

    PubMed

    Polo, Efrain; Trilleras, Jorge; Ramos, Juan; Galdámez, Antonio; Quiroga, Jairo; Gutierrez, Margarita

    2016-01-01

    A small series of tetrahydroindazoles was prepared, starting from 2-acetylcyclohexanone and different hydrazines using reflux and a focused microwave reactor. Microwave irradiation (MW) favored the formation of the desired products with improved yields and shortened reaction times. This is a simple and green method for the synthesis of substituted tetrahydroindazole derivatives. The in vitro antioxidant activity was evaluated using the DPPH and ABTS methods. In these assays, 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) showed moderate DPPH decoloring activity, while 3-methyl-4,5,6,7-tetrahydro-1H-indazole (3a), 3-methyl-2-phenyl-4,5,6,7-tetrahydro-2H-indazole (3b) and 2-(4-fluorophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-indazole (3f) were the most active in the ABTS assay. All compounds were well characterized by IR, ¹H-, (13)C-NMR and GC-MS spectroscopy and physical data, while the structure of 4-(3-methyl-4,5,6,7-tetrahydro-2H-indazol-2-yl)benzoic acid (3e) was also determined by single crystal X-ray analysis. PMID:27409599

  2. Highly efficient and regioselective synthesis of dihydromyricetin esters by immobilized lipase.

    PubMed

    Li, Wei; Wu, Huan; Liu, Benguo; Hou, Xuedan; Wan, Duanji; Lou, Wenyong; Zhao, Jian

    2015-04-10

    Dihydromyricetin is the principle component of the Chinese herbal tea Teng-cha and a promising ingredient for functional food and nutraceuticals, but its low solubility limits its application potentials. This study explored enzymatic acylation of dihydromyricetin to improve its solubility in lipid systems. Acylation was achieved with several lipases with the synthesis of a major (>86%) product and a minor product. Isolation and purification of the products by preparative HPLC followed by LC-MS, (13)C NMR, (1)H NMR and 2 D-HSQC NMR analyses showed that the major product was a dihydromyricetin monoester with the acylation site at the 3-OH group of C ring. Quantum chemical calculations revealed that the 3-OH had the lowest antioxidant activity, and therefore acylation at this site was expected to have minimum impact on the antioxidant activity. Several factors, including solvent, acyl donor, enzyme origin, molar ratio of substrates and reaction temperature and time, exhibited significant effects on the initial rate, conversion yield and regioselectivity of the reaction. Acylation occurred only with vinyl acetate as the acyl donor, and highest conversion yields were achieved with immobilized Penicillium expansum lipase and Novozyme 435 with DMSO and acetonitrile being the best solvents. In general, the acylation results were found to be superior to previous reports on acylation of aglycone flavonoids with respects to conversion yield and regioselectivity. PMID:25701177

  3. Efficient synthesis and activity of beneficial intestinal flora of two lactulose-derived oligosaccharides.

    PubMed

    Zhu, Zhen-Yuan; Cui, Di; Gao, Hui; Dong, Feng-Ying; Liu, Xiao-Cui; Liu, Fei; Chen, Lu; Zhang, Yong-Min

    2016-05-23

    Lactulose is considered as a prebiotic because it promotes the intestinal proliferation of Lactobacillus acidophilus which is added to various milk products. Moreover, lactulose is used in pharmaceuticals as a gentle laxative and to treat hyperammonemia. This study was aimed at the total synthesis of two Lactulose-derived oligosaccharides: one is 3-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,3-glycosidic bound, the other is 1-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,1-glycosidic bound, which were accomplished in seven steps from d-fructose and β-d-galactose and every step of yield above 75%. This synthetic route provided a practical and effective synthetic strategy for galactooligosaccharides, starting from commercially available monosaccharides. Then we evaluated on their prebiotic properties in the search for potential agents of regulating and improving the intestinal flora of human. The result showed that the prebiotic properties of Lactulose-derived oligosaccharides was much better than Lactulose. Among them, 3-O-β-d-galactopyranosyl-d-fructose displayed the most potent activity of proliferation of L. acidophilus. PMID:26974370

  4. Gene cloning and molecular characterization of the Talaromyces thermophilus lipase catalyzed efficient hydrolysis and synthesis of esters.

    PubMed

    Romdhane, Ines Belhaj-Ben; Frikha, Fakher; Maalej-Achouri, Inès; Gargouri, Ali; Belghith, Hafedh

    2012-02-15

    A genomic bank from Talaromyces thermophilus fungus was constructed and screened using a previously isolated fragment lipase gene as probe. From several clones isolated, the nucleotide sequence of the lipase gene (TTL gene) was completed and sequenced. The TTL coding gene consists of an open reading frame (ORF) of 1083bp encoding a protein of 269 Aa with an estimated molecular mass of 30kDa. The TTL belongs to the same gene family as Thermomyces lanuginosus lipase (TLL, Lipolase®), a well known lipase with multiple applications. The promoter sequence of the TTL gene showed the conservation of known consensus sequences PacC, CreA, Hap2-3-4 and the existence of a particular sequence like the binding sites of Oleate Response Element (ORE) and Fatty acids Responsis Element (FARE) which are similar to that already found to be specific of lipolytic genes in Candida and Fusarium, respectively. Northern blot analysis showed that the TTL expression was much higher on wheat bran than on olive oil as sole carbon source. Compared to the Lipolase®, this enzyme was found to be more efficient for the hydrolysis and the synthesis of esters; and its synthetic efficiency even reached 91.6% from Waste Cooking Oil triglycerides. PMID:22178764

  5. Green synthesis of highly efficient CdSe quantum dots for quantum-dots-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Gao, Bing; Shen, Chao; Zhang, Bo; Zhang, Mengya; Yuan, Shuanglong; Yang, Yunxia; Chen, Guorong

    2014-05-01

    Green synthesis of CdSe quantum dots for application in the quantum-dots-sensitized solar cells (QDSCs) is investigated in this work. The CdSe QDs were prepared with glycerol as the solvent, with sharp emission peak, full width at half maximum around 30 nm, and absorption peak from 475 nm to 510 nm. The reaction is environmental friendly and energy saving. What's more, the green synthesized CdSe QDs are coherence to the maximum remittance region of the solar spectrum and suitable as sensitizers to assemble onto TiO2 electrodes for cell devices application. What's more, the dynamic procedure of the carriers' excitation, transportation, and recombination in the QDSCs are discussed. Because the recombination of the electrons from the conduction band of TiO2's to the electrolyte affects the efficiency of the solar cells greatly, 3-Mercaptopropionic acid capped water-dispersible QDs were used to cover the surface of TiO2. The resulting green synthesized CdSe QDSCs with Cu2S as the electrode show a photovoltaic performance with a conversion efficiency of 3.39%.

  6. Electrochemical synthesis of fractal bimetallic Cu/Ag nanodendrites for efficient surface enhanced Raman spectroscopy.

    PubMed

    Li, Da; Liu, Jingquan; Wang, Hongbin; Barrow, Colin J; Yang, Wenrong

    2016-09-21

    Here, we for the first time synthesized bimetallic Cu/Ag dendrites on graphene paper (Cu/Ag@G) using a facile electrodeposition method to achieve efficient SERS enhancement. Cu/Ag@G combined the electromagnetic enhancement of Cu/Ag dendrites and the chemical enhancement of graphene. SERS was ascribed to the rough metal surface, the synergistic effect of copper and silver nanostructures and the charge transfer between graphene and the molecules. PMID:27522964

  7. Dioxazoles, a new mild nitrene transfer reagent in gold catalysis: highly efficient synthesis of functionalized oxazoles.

    PubMed

    Chen, Ming; Sun, Ning; Chen, Haoyi; Liu, Yuanhong

    2016-05-01

    A gold-catalyzed regioselective [3+2] cycloaddition of ynamides with 1,4,2-dioxazoles was developed and offers a novel approach to obtain highly functionalized oxazoles under mild reaction conditions. 1,4,2-Dioxazole was found to act as an efficient N-acyl nitrene equivalent to trigger a facile generation of α-imino gold-carbene intermediate through the elimination of a ketone. PMID:27086554

  8. Stereoselective Halogenation of Integral Unsaturated C-C Bonds in Chemically and Mechanically Robust Zr and Hf MOFs.

    PubMed

    Marshall, Ross J; Griffin, Sarah L; Wilson, Claire; Forgan, Ross S

    2016-03-24

    Metal-organic frameworks (MOFs) containing Zr(IV) -based secondary building units (SBUs), as in the UiO-66 series, are receiving widespread research interest due to their enhanced chemical and mechanical stabilities. We report the synthesis and extensive characterisation, as both bulk microcrystalline and single crystal forms, of extended UiO-66 (Zr and Hf) series MOFs containing integral unsaturated alkene, alkyne and butadiyne units, which serve as reactive sites for postsynthetic modification (PSM) by halogenation. The water stability of a Zr-stilbene MOF allows the dual insertion of both -OH and -Br groups in a single, aqueous bromohydrination step. Quantitative bromination of alkyne- and butadiyne-containing MOFs is demonstrated to be stereoselective, as a consequence of the linker geometry when bound in the MOFs, while the inherent change in hybridisation and geometry of integral linker atoms is facilitated by the high mechanical stabilities of the MOFs, allowing bromination to be characterised in a single-crystal to single-crystal (SCSC) manner. The facile addition of bromine across the unsaturated C-C bonds in the MOFs in solution is extended to irreversible iodine sequestration in the vapour phase. A large-pore interpenetrated Zr MOF demonstrates an I2 storage capacity of 279 % w/w, through a combination of chemisorption and physisorption, which is comparable to the highest reported capacities of benchmark iodine storage materials for radioactive I2 sequestration. We expect this facile PSM process to not only allow trapping of toxic vapours, but also modulate the mechanical properties of the MOFs. PMID:26916707

  9. The Synthesis of Organic Molecules of Intrinsic Microporosity Designed to Frustrate Efficient Molecular Packing

    PubMed Central

    Taylor, Rupert G. D.; Bezzu, C. Grazia; Carta, Mariolino; Msayib, Kadhum J.; Walker, Jonathan; Short, Rhys; Kariuki, Benson M.

    2016-01-01

    Abstract Efficient reactions between fluorine‐functionalised biphenyl and terphenyl derivatives with catechol‐functionalised terminal groups provide a route to large, discrete organic molecules of intrinsic microporosity (OMIMs) that provide porous solids solely by their inefficient packing. By altering the size and substituent bulk of the terminal groups, a number of soluble compounds with apparent BET surface areas in excess of 600 m2 g−1 are produced. The efficiency of OMIM structural units for generating microporosity is in the order: propellane>triptycene>hexaphenylbenzene>spirobifluorene>naphthyl=phenyl. The introduction of bulky hydrocarbon substituents significantly enhances microporosity by further reducing packing efficiency. These results are consistent with findings from previously reported packing simulation studies. The introduction of methyl groups at the bridgehead position of triptycene units reduces intrinsic microporosity. This is presumably due to their internal position within the OMIM structure so that they occupy space, but unlike peripheral substituents they do not contribute to the generation of free volume by inefficient packing. PMID:26751824

  10. Dispersion-precipitation synthesis of nanosized magnetic iron oxide for efficient removal of arsenite in water.

    PubMed

    Cheng, Wei; Xu, Jing; Wang, Yajie; Wu, Feng; Xu, Xiuyan; Li, Jinjun

    2015-05-01

    Nanosized magnetic iron oxide was facilely synthesized by a dispersion-precipitation method, which involved acetone-promoted precipitation of colloidal hydrous iron oxide nanoparticles and subsequent calcination of the precipitate at 250°C. Characterization by X-ray diffraction, transmission electron microscopy, Raman spectroscopy, nitrogen sorption, and vibrating-sample magnetometry revealed that the material was a composite of α-Fe2O3 and γ-Fe2O3 with primary particle size of 15-25 nm and specific surface area of 121 m(2)/g, as well as superparamagnetic property. The material was used as adsorbent for the removal of arsenite in water. Batch experiments showed that the adsorption isotherms at pH 3.0-11.0 fit the Langmuir equation and the adsorption obeys pseudo-second-order kinetics. Its maximum sorption capability for arsenite is 46.5 mg/g at pH 7.0. Coexisting nitrate, carbonate, sulfate, chloride, and fluoride have no significant effect on the removal efficiency of arsenite, while phosphate and silicate reduce the removal efficiency to some extent. The As(III) removal mechanism is chemisorption through forming inner-sphere surface complexes. The efficiency of arsenic removal is still maintained after five cycles of regeneration-reuse. PMID:25612934

  11. Asymmetric Total Synthesis of Propindilactone G, Part 2: Enantioselective Construction of the Fully Functionalized BCDE Ring System.

    PubMed

    Zhang, Jia-Jun; You, Lin; Wang, Yue-Fan; Li, Yuan-He; Liang, Xin-Ting; Zhang, Bo; Yang, Shou-Liang; Su, Qi; Chen, Jia-Hua; Yang, Zhen

    2016-05-01

    The enantioselective synthesis of the fully functionalized BCDE tetracyclic ring system of propindilactone G (A) is reported. Several synthetic methods were developed and applied to achieve this goal, including: 1) an asymmetric Diels-Alder reaction in the presence of Hayashi's catalyst for the synthesis of optically pure key intermediate 3; 2) an intramolecular Pauson-Khand reaction (PKR) for the stereoselective synthesis of the BCDE ring with an all-carbon chiral quaternary center at the C13 position by using the TMS-substituted acetylene as the substrate; and 3) Pd-catalyzed reductive hydrogenolysis for the stereoselective synthesis of the fully functionalized BCDE tetracyclic ring system. The chemistry developed herein provided a greater understanding of the total synthesis propindilactone G (A) and its analogues. PMID:26991420

  12. Polyvinyl alcohol: an efficient fuel for synthesis of superparamagnetic LSMO nanoparticles for biomedical application.

    PubMed

    Thorat, N D; Shinde, K P; Pawar, S H; Barick, K C; Betty, C A; Ningthoujam, R S

    2012-03-14

    La(0.7)Sr(0.3)MnO(3) (LSMO) nanoparticles have been prepared using glycine and polyvinyl alcohol (PVA) as fuels. Their crystal structure, particle morphology and compositions are characterized using X-ray diffraction, transmission electron microscopy, field-emission electron microscopy and energy dispersive analysis of X-ray. They show a pseudo-cubic perovskite structure. The spherical particle sizes of 30 and 20 nm have been obtained from samples prepared by glycine and PVA respectively. The field cooled (FC) and zero field cooled (ZFC) magnetizations have been recorded from 5 to 375 K at 500 Oe and superparamagnetic blocking temperatures (T(B)) of 75 and 30 K are obtained from samples prepared by glycine and PVA respectively. Particle size distribution is observed from dynamic light scattering measurements. Dispersion stability of the particles in water is studied by measuring the Zeta potential with varying the pH of the medium from 1 to 12. Under induction heating experiments, a hyperthermia temperature (42-43 °C) is achieved by both the samples (3-6 mg mL(-1)) at magnetic fields of 167-335 Oe and at a frequency of 267 kHz. The bio-compatibility of the LSMO nanoparticles is studied on the L929 and HeLa cell lines by MTT assay for up to 48 h. The present work reveals the importance of synthesis technique and fuel choice on structural, morphological, magnetic, hyperthermia and biocompatible properties of LSMO and predicts the suitability for biomedical applications. PMID:22277953

  13. An efficient synthesis of porphyrins with different meso substituents that avoids scrambling in aqueous media.

    PubMed

    Nowak-Król, Agnieszka; Plamont, Rémi; Canard, Gabriel; Edzang, Judicaelle Andeme; Gryko, Daniel T; Balaban, Teodor Silviu

    2015-01-19

    We have developed new conditions that afford regioisomerically pure trans-A2B2-, A3B-, and trans-AB2C-porphyrins bearing aryl and arylethynyl substituents. The porphyrins were prepared by the acid-catalyzed condensation of dipyrromethanes with aldehydes followed by oxidation with p-chloranil or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Optimal conditions for the condensation were identified after examining various reaction parameters such as solvent composition, acid concentration, and reaction time. The conditions identified (for aromatic aldehydes: EtOH/H2O 4:1, [DPM] = 4 mM, [aldehyde] = 4 mM, [HCl] = 38 mM, 16 h; for arylethynyl aldehydes: THF/H2O 2:1, [DPM] = 13 mM, [aldehyde] = 13 mM, [HCl] = 150 mM, 3 h) resulted in the formation of porphyrins in yields of 9-38% without detectable scrambling. This synthesis is compatible with diverse functionalities such as ester or nitrile. In total, 20 new trans-A2B2-, A3B-, and trans-AB2C-porphyrins were prepared. The scope and limitations of the two sets of reaction conditions have been explored. The methodological advantage of this approach is its straightforward access to building blocks and the formation of the porphyrin core in higher yields than by any other methodology and by using environmentally benign and nonhazardous chemicals. PMID:25417808

  14. Ammonium iodide-induced sulfonylation of alkenes with DMSO and water toward the synthesis of vinyl methyl sulfones.

    PubMed

    Gao, Xiaofang; Pan, Xiaojun; Gao, Jian; Huang, Huawen; Yuan, Gaoqing; Li, Yingwei

    2015-01-01

    A novel ammonium iodide-induced sulfonylation of alkenes with DMSO and water toward the synthesis of vinyl methyl sulfones is described. The process proceeded smoothly under metal-free conditions with high stereoselectivity and good functional group tolerance. The reaction mechanism was revealed to proceed through a domino reaction of oxidation and elimination after the radical addition to alkenes. PMID:25406694

  15. Concise Synthesis of (2R,4R)-Monatin.

    PubMed

    Amino, Yusuke

    2016-01-01

    Monatin, 4-hydroxy-4-(3-indolylmethyl)-glutamic acid, is a naturally occurring sweet amino acid. The (2R,4R)-monatin isomer has been found to be the sweetest among its four stereoisomers. A concise and efficient synthesis of (2R,4R)-monatin was accomplished by the alkylation of (4R)-N-tert-butoxycarbonyl (tBoc)-4-tert-butyldimethylsilyoxy-D-pyroglutamic acid methyl ester with tert-butyl 3-(bromomethyl)-1H-indole-1-carboxylate to give (4R)-N-tBoc-4-tert-butyldimethylsilyloxy-4-(N-tBoc-3-indolylmethyl)-D-pyroglutamic acid methyl ester, i.e., the lactam form of (2R,4R)-monatin with protecting groups. This was followed by the hydrolysis of the lactam ring and deprotection. The 4-hydroxyl D-pyroglutamic acid derivative was demonstrated to be a suitable precursor for the efficient preparation of (2R,4R)-monatin in high optical purity because the alkylation proceeded in regioselective and stereoselective manners at C4 to form appropriate asymmetric tetra-substituted carbon center; the resulting alkylated pyroglutamic acid derivative was then easily converted into the linear form of monatin. PMID:27477667

  16. Gold-catalyzed homogeneous oxidative C-O bond formation: efficient synthesis of 1-benzoxyvinyl ketones.

    PubMed

    Peng, Yu; Cui, Li; Zhang, Guozhu; Zhang, Liming

    2009-04-15

    A novel Au-catalyzed homogeneous oxidative C-O bond-forming reaction involving a Au(I)/Au(III) catalytic cycle is developed. Mechanistic studies reveal the involvement of a unique intramolecular carboxy migration. From readily available propargylic benzoates, this chemistry allows efficient access to captodative alkenes and dienones, demonstrating the synthetic potential of incorporating Au(I)/Au(III) catalytic cycles into contemporary Au chemistry. The unique reactivity and the mechanistic insights would help open a new research area in gold catalysis. PMID:19301899

  17. Design and synthesis of molecular donors for solution-processed high-efficiency organic solar cells.

    PubMed

    Coughlin, Jessica E; Henson, Zachary B; Welch, Gregory C; Bazan, Guillermo C

    2014-01-21

    Organic semiconductors incorporated into solar cells using a bulk heterojunction (BHJ) construction show promise as a cleaner answer to increasing energy needs throughout the world. Organic solar cells based on the BHJ architecture have steadily increased in their device performance over the past two decades, with power conversion efficiencies reaching 10%. Much of this success has come with conjugated polymer/fullerene combinations, where optimized polymer design strategies, synthetic protocols, device fabrication procedures, and characterization methods have provided significant advancements in the technology. More recently, chemists have been paying particular attention to well-defined molecular donor systems due to their ease of functionalization, amenability to standard organic purification and characterization methods, and reduced batch-to-batch variability compared to polymer counterparts. There are several critical properties for efficient small molecule donors. First, broad optical absorption needs to extend towards the near-IR region to achieve spectral overlap with the solar spectrum. Second, the low lying highest occupied molecular orbital (HOMO) energy levels need to be between -5.2 and -5.5 eV to ensure acceptable device open circuit voltages. Third, the structures need to be relatively planar to ensure close intermolecular contacts and high charge carrier mobilities. And last, the small molecule donors need to be sufficiently soluble in organic solvents (≥10 mg/mL) to facilitate solution deposition of thin films of appropriate uniformity and thickness. Ideally, these molecules should be constructed from cost-effective, sustainable building blocks using established, high yielding reactions in as few steps as possible. The structures should also be easy to functionalize to maximize tunability for desired properties. In this Account, we present a chronological description of our thought process and design strategies used in the development of highly

  18. Total synthesis of legionaminic acid as basis for serological studies.

    PubMed

    Matthies, Stefan; Stallforth, Pierre; Seeberger, Peter H

    2015-03-01

    Legionaminic acid is a nine-carbon diamino monosaccharide that is found coating the surface of various bacterial human pathogens. Its unique structure makes it a valuable biological probe, but access via isolation is difficult and no practical synthesis has been reported. We describe a stereoselective synthesis that yields a legionaminic acid building block as well as linker-equipped conjugation-ready legionaminic acid starting from cheap d-threonine. To set the desired amino and hydroxyl group pattern of the target, we designed a concise sequence of stereoselective reactions. The key transformations rely on chelation-controlled organometallic additions and a Petasis multicomponent reaction. The legionaminic acid was synthesized in a form that enables attachment to surfaces. Glycan microarray containing legionaminic acid revealed that human antibodies bind the synthetic glycoside. The synthetic bacterial monosaccharide is a valuable probe to detect an immune response to bacterial pathogens such as Legionella pneumophila, the causative agent of Legionnaire's disease. PMID:25668389

  19. Synthesis and characterization of VO2-based thermochromic thin films for energy-efficient windows.

    PubMed

    Batista, Carlos; Ribeiro, Ricardo M; Teixeira, Vasco

    2011-01-01

    Thermochromic VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC and pulsed-DC magnetron sputtering. The influence of substitutional doping of V by higher valence cations, such as W, Mo, and Nb, and respective contents on the crystal structure of VO2 is evaluated. Moreover, the effectiveness of each dopant element on the reduction of the intrinsic transition temperature and infrared modulation efficiency of VO2 is discussed. In summary, all the dopant elements--regardless of the concentration, within the studied range-- formed a solid solution with VO2, which was the only compound observed by X-ray diffractometry. Nb showed a clear detrimental effect on the crystal structure of VO2. The undoped films presented a marked thermochromic behavior, specially the one prepared by pulsed-DC sputtering. The dopants effectively decreased the transition of VO2 to the proximity of room temperature. However, the IR modulation efficiency is markedly affected as a consequence of the increased metallic character of the semiconducting phase. Tungsten proved to be the most effective element on the reduction of the semiconducting-metal transition temperature, while Mo and Nb showed similar results with the latter being detrimental to the thermochromism. PMID:21711813

  20. Synthesis and characterization of VO2-based thermochromic thin films for energy-efficient windows

    PubMed Central

    2011-01-01

    Thermochromic VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC and pulsed-DC magnetron sputtering. The influence of substitutional doping of V by higher valence cations, such as W, Mo, and Nb, and respective contents on the crystal structure of VO2 is evaluated. Moreover, the effectiveness of each dopant element on the reduction of the intrinsic transition temperature and infrared modulation efficiency of VO2 is discussed. In summary, all the dopant elements--regardless of the concentration, within the studied range-- formed a solid solution with VO2, which was the only compound observed by X-ray diffractometry. Nb showed a clear detrimental effect on the crystal structure of VO2. The undoped films presented a marked thermochromic behavior, specially the one prepared by pulsed-DC sputtering. The dopants effectively decreased the transition of VO2 to the proximity of room temperature. However, the IR modulation efficiency is markedly affected as a consequence of the increased metallic character of the semiconducting phase. Tungsten proved to be the most effective element on the reduction of the semiconducting-metal transition temperature, while Mo and Nb showed similar results with the latter being detrimental to the thermochromism. PMID:21711813