Noncovalent Interactions in the Asymmetric Synthesis of Rigid, Conjugated Helical Structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyasaka, Makoto; Pink, Maren; Rajca, Suchada

Tetrakis({beta}-trithiophene) 1 folds into a helical conformation (RRR) that facilitates double ring annelation, with high diastereoselectivity and modest enantioselectivity, to provide bis[7]helicene 2 (MRM). This rigid, helically locked structure has enhanced chiroptical properties similar to the corresponding [15]helicene.

Cross-Aldol Reaction of Activated Carbonyls with Nitrosocarbonyl Intermediates: Stereoselective Synthesis toward α-Hydroxy-β-amino Esters and Amides.

PubMed

Mallik, Sumitava; Bhajammanavar, Vinod; Ramakrishna, Isai; Baidya, Mahiuddin

2017-07-21

A practical and flexible strategy toward α-hydroxy-β-amino esters and amides, which are important biological motifs, based on an organocatalytic cross-aldol reaction of in situ-generated nitrosocarbonyl intermediates followed by hydrogenation is presented. The protocol features operational simplicity, high yields, a wide substrate scope, and high regio- and diastereoselectivity profiles. The utility of this method was showcased through the synthesis of bestatin analogues and indole formation.

Stereoselective Synthesis of Highly Functionalized α-Diazo-β-ketoalkanoates via Catalytic Onepot Mukaiyama-Aldol Reactions

PubMed Central

Zhou, Lei; Doyle, Michael P.

2010-01-01

Methyl diazoacetoacetate undergoes zinc triflate catalyzed condensation with a broad selection of aldehydes to produce δ-siloxy-α-diazo-β-ketoalkanoates in good yield, and δ-hydroxy-α-diazo-β-ketoalkanoates are formed with high diastereoselectivity in reactions with α-diazo-β-ketopentanoate promoted by dibutylboron triflate. PMID:20102172

Synthesis of pyroglutamic acid derivatives via double michael reactions of alkynones.

PubMed

Scansetti, Myriam; Hu, Xiangping; McDermott, Benjamin P; Lam, Hon Wai

2007-05-24

In the presence of substoichiometric quantities of potassium tert-butoxide and an additional metal salt, amide-tethered diacids undergo double Michael reactions with alkynones to provide highly functionalized pyroglutamic acid derivatives. The metal salt was found to play an important role in improving the diastereoselectivities of the reactions.

One-Pot Catalytic Enantio- and Diastereoselective Syntheses of anti-, syn-cis-Disubstituted, and syn-Vinyl Cyclopropyl Alcohols

PubMed Central

Kim, Hun Young; Salvi, Luca; Carroll, Patrick J.; Walsh, Patrick J.

2009-01-01

Highly enantio- and diastereoselective methods for the synthesis of a variety of cyclopropyl alcohols are reported. These methods represent the first one-pot approaches to syn-vinyl cyclopropyl alcohols, syn-cis-disubstituted cyclopropyl alcohols, and anti-cyclopropyl alcohols from achiral precursors. The methods begin with enantioselective C–C bond formations promoted by a MIB-based zinc catalyst to generate allylic alkoxide intermediates. The intermediates are then subjected to in situ alkoxide-directed cyclopropanation to provide cyclopropyl alcohols. In the synthesis of vinyl cyclopropyl alcohols, hydroboration of enynes is followed by transmetalation of the resulting dienylborane to zinc to provide dienylzinc reagents. Enantioselective addition to aldehydes generates the requisite dienyl zinc alkoxides, which are then subjected to in situ cyclopropanation to furnish vinyl cyclopropyl alcohols. Cyclopropanation occurs at the double bond allylic to the alkoxide. Using this method, syn-vinylcyclopropyl alcohols are obtained in 65–85% yield, 76–93% ee, and >19:1 dr. To prepare anti-cyclopropanols, enantioselective addition of alkylzinc reagents to conjugated enals provides allylic zinc alkoxides. Because direct cyclopropanation provides syn-cyclopropyl alcohols, the intermediate allylic alkoxides were treated with TMSCl/Et3N to generate intermediate silyl ethers. In situ cyclopropanation of the allylic silyl ether resulted in cyclopropanation to form the anti-cyclopropyl silyl ether. Workup with TBAF affords the anti-cyclopropyl alcohols in one-pot in 60–82% yield, 89–99% ee, and ≥10:1 dr. For the synthesis of cis-disubstituted cyclopropyl alcohols, in situ generated (Z)-vinyl zinc reagents were employed in asymmetric addition to aldehydes to generate (Z)-allylic zinc alkoxides. In situ cyclopropanation provides syn-cis-disubstituted cyclopropyl alcohols in 42–70% yield, 88–97% ee, and >19:1 dr. These one-pot procedures enable the synthesis of a diverse array of cyclopropyl alcohol building blocks with high enantio- and diastereoselectivities. PMID:19954146

Catalytic stereoselective synthesis of highly substituted indanones via tandem Nazarov cyclization and electrophilic fluorination trapping.

PubMed

Nie, Jing; Zhu, Hong-Wei; Cui, Han-Feng; Hua, Ming-Qing; Ma, Jun-An

2007-08-02

A new catalytic stereoselective tandem transformation via Nazarov cyclization/electrophilic fluorination has been accomplished. This sequence is efficiently catalyzed by a Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity (trans/cis up to 49/1). Three examples of catalytic enantioselective tandem transformation are presented.

Diastereoselective synthesis of furanose and pyranose substituted glycine and alanine derivatives via proline-catalyzed asymmetric α-amination of aldehydes.

PubMed

Petakamsetty, Ramu; Ansari, Anas; Ramapanicker, Ramesh

2016-11-29

A concise organocatalytic route toward the synthesis of furanose and pyranose substituted glycine and alanine derivatives is reported. These compounds are core structural units of some of the naturally available antibiotics and antifungal agents. Proline-catalyzed asymmetric α-amination of aldehydes derived from sugars is used as the key reaction to synthesize twelve sugar amino acid derivatives. The asymmetric transformations proceeded in good yields and with good to excellent diastereoselectivity. The application of the synthesized amino acids is demonstrated by synthesizing a tripeptide containing one of them. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diversity oriented synthesis of tricyclic compounds from glycals using the Ferrier and the Pauson-Khand reactions.

PubMed

Hotha, Srinivas; Tripathi, Ashish

2005-01-01

Diversity oriented synthesis of tricyclic compounds was achieved using a combination of the Ferrier reaction and the Pauson-Khand reaction. Ferrier reaction was effected using NbCl5, and the Pauson-Khand reaction was carried out using Co2(CO)8, acetonitrile-dimethoxyethane. Michael additions using various alkyl, aryl, and heterocyclic thiols were also performed successfully. The Ferrier, Pauson-Khand, and Michael addition reactions were found to be highly diastereoselective.

Pd-catalyzed arylation reactions with phenol diazonium salts: application in the synthesis of diarylheptanoids.

PubMed

Schmidt, Bernd; Hölter, Frank; Kelling, Alexandra; Schilde, Uwe

2011-05-06

The first total synthesis of the natural product (3S,7R)-5,6-dehydro-de-O-methyl centrolobine and various analogues is reported, using a highly regio- and diastereoselective Mizoroki-Heck reaction of phenol diazonium salts and enantiopure dihydropyrans. The assigned relative configuration was confirmed by single-crystal X-ray structure analysis, but a revision of the absolute configuration is proposed based on polarimetric measurement. © 2011 American Chemical Society

Synthesis of the BCDE molecular fragment of azadiradione mediated by titanocene(III).

PubMed

Fernández-Mateos, A; Madrazo, S Encinas; Teijón, P Herrero; Clemente, R Rabanedo; González, R Rubio; González, F Sanz

2013-10-04

A practical, short, and diastereoselective synthesis of the azadiradione BCDE fragment from a readily available starting material is described. The key step was the titanocene(III)-promoted tandem cyclization of unsaturated epoxy nitrile.

Enantiopure Ferrocene-Based Planar-Chiral Iridacycles: Stereospecific Control of Iridium-Centred Chirality.

PubMed

Arthurs, Ross A; Ismail, Muhammad; Prior, Christopher C; Oganesyan, Vasily S; Horton, Peter N; Coles, Simon J; Richards, Christopher J

2016-02-24

Reaction of [IrCp*Cl2 ]2 with ferrocenylimines (Fc=NAr, Ar=Ph, p-MeOC6 H4 ) results in ferrocene C-H activation and the diastereoselective synthesis of half-sandwich iridacycles of relative configuration Sp *,RIr *. Extension to (S)-2-ferrocenyl-4-(1-methylethyl)oxazoline gave highly diastereoselective control over the new elements of planar chirality and metal-based pseudo-tetrahedral chirality, to give both neutral and cationic half-sandwich iridacycles of absolute configuration Sc ,Sp ,RIr . Substitution reactions proceed with retention of configuration, with the planar chirality controlling the metal-centred chirality through an iron-iridium interaction in the coordinatively unsaturated cationic intermediate. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Macrocyclic β-Iodoallenolate Intermediate is Key: Synthesis of the ABD Core of Phomactin A

PubMed Central

Ciesielski, Jennifer; Cariou, Kevin

2012-01-01

An enantioselective strategy for the synthesis of phomactin natural products is described. The Lewis acid-triggered cyclization of a β-iodoallenolate embedded in a 12-membered macrocycle was used to obtain a highly functionalized bicyclo[9.3.1]pentadecane in good yield and high diastereoselectivity. This iodoenone contains the substituents of the AD ring system of the phomactin family of natural products, appropriate for further functionalization. Synthesis of the oxadecalin core of phomactin A from the AD iodoenone intermediate was achieved. In this unusual strategy, rings A and B are both fashioned within a macrocyclic precursor. PMID:22853449

Lewis-Base-Mediated Diastereoselective Silylations of Alcohols: Synthesis of Silicon-Stereogenic Dialkoxysilanes Controlled by Chiral Aryl BINMOLs.

PubMed

Bai, Xing-Feng; Zou, Jin-Feng; Chen, Mu-Yi; Xu, Zheng; Li, Li; Cui, Yu-Ming; Zheng, Zhan-Jiang; Xu, Li-Wen

2017-07-18

In the past years, stereoselective functionalizations of hydroxyl groups of alcohol substrates with chlorosilanes leading to silyl ether formation have evolved from a functional-group protection to an enantioselective synthetic strategy. This work comprises a controlled desymmetrization of dichlorosilanes by using a family of structurally specific chiral diols, chiral 1,1'-binaphthalene-2-α-arylmethanol-2'-ol (Ar-BINMOL). This process led to the facile construction of silicon-stereogenic organosilicon compounds with high yields and good diastereoselectivities. In addition, the diasteroselective silylation of chiral diols might not only be of interest for the development of highly stereoselective nucleophilic silylation, but also shed light on the construction of novel chiral phosphine ligands bearing a silicon-stereogenic center. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient synthesis of optically active 4-nitro-cyclohexanones via bifunctional thiourea-base catalyzed double-Michael addition of nitromethane to dienones.

PubMed

Wu, Bin; Liu, Guo-Gui; Li, Mei-Qiu; Zhang, Yong; Zhang, Shao-Yun; Qiu, Jun-Ru; Xu, Xiao-Ping; Ji, Shun-Jun; Wang, Xing-Wang

2011-04-07

Thiourea-modified cinchona alkaloids as bifunctional catalysts and a base could catalyze a stepwise [5+1] cyclization of divinyl ketones with nitromethane via double Michael additions, furnishing optically active 4-nitro-cyclohexanones with good yields, excellent diastereoselectivities (>20 : 1) and high enantiomeric ratios (up to 97 : 3).

Pyrrolidinones derived from (S)-pyroglutamic acid: penmacric acid and analogues.

PubMed

Anwar, Muhammed; Bailey, Jonathan H; Dickinson, Laura C; Edwards, Hermia J; Goswami, Rajesh; Moloney, Mark G

2003-07-07

Alkylation reactions using alpha-halolactams or lactam enolates derived from bicyclic lactam templates can proceed with high endo- or exo- diastereoselectivity respectively. In the latter case, stereochemical correction by means of enolate generation and hindered phenol quench is possible with moderate efficiency. This protocol has been applied to the synthesis of protected penmacric acid and its analogues.

Stereodivergent Aminocatalytic Synthesis of Z- and E-Trisubstituted Double Bonds from Alkynals.

PubMed

Marzo, Leyre; Luis-Barrera, Javier; Mas-Ballesté, Rubén; Ruano, José Luis García; Alemán, José

2016-11-07

A highly diastereoselective synthesis of trisubstituted Z- or E-enals, which are important intermediates in organic synthesis, as well as being present in natural products, is described using different alkynals and nucleophiles as starting materials. Diastereocontrol is mainly governed by the appropriate catalyst. Therefore, those reactions controlled by steric effects, such as the Jørgensen-Hayashi's catalyst, give access to E isomers, and those catalysts that facilitate hydrogen bonding, such as tetrazol-pyrrolidine Ley's catalyst, allow the synthesis of Z isomers. A stereochemical model based on DFT calculations is proposed. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of (±)-Tetrapetalone A-Me Aglycon**

PubMed Central

Carlsen, Peter N.; Mann, Tyler J.; Hoveyda, Amir H.

2014-01-01

The first synthesis of (±)-tetrapetalone A-Me aglycon is described. Key bond-forming reactions include Nazarov cyclization, a ring-closing metathesis (RCM) promoted with complete diastereoselectivity by a chiral Mo-based complex, tandem conjugate reduction-intramolecular aldol cyclization, and oxidative dearomatization. PMID:25045072

A Catalytic Asymmetric Synthesis of Polysubstituted Piperidines Using a Rhodium (I) Catalyzed [2+2+2] Cycloaddition Employing a Cleavable Tether

PubMed Central

Martin, Timothy J.; Rovis, Tomislav

2013-01-01

An enantioselective rhodium (I) catalyzed [2+2+2] cycloaddition with a cleavable tether has been developed. The reaction proceeds with a variety of alkyne substrates in good yield and high enantioselectivity. Upon reduction of the vinylogous amide in high diastereoselectivity (>19:1) and cleavage of the tether, N-methylpiperidine products with functional group handles can be accessed. PMID:23606664

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

PubMed Central

Westphal, Julia C

2014-01-01

Summary A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide. PMID:24605158

Phosphate Tether-Mediated Approach to the Formal Total Synthesis of (-)-Salicylihalamides A and B

PubMed Central

Chegondi, Rambabu; Tan, Mary M. L.; Hanson, Paul R.

2011-01-01

A concise formal synthesis of the cytotoxic macrolides (-)-salicylihalamides A and B is reported. Key features of the synthetic strategy include a chemoselective hydroboration, highly regio- and diastereoselective methyl cuprate addition, Pd-catalyzed formate reduction, and an E-selective ring-closing metathesis to construct the 12-membered macrocycle subunit. Overall, two routes have been developed from a readily prepared bicyclic phosphate (4-steps), a 13-step route and a more efficient 9-step sequence relying on regioselective esterification of a key diol. PMID:21504150

One-pot Diels–Alder cycloaddition/gold(I)-catalyzed 6-endo-dig cyclization for the synthesis of the complex bicyclo[3.3.1]alkenone framework

PubMed Central

Sow, Boubacar; Bellavance, Gabriel; Barabé, Francis

2011-01-01

Summary The rapid synthesis of bicyclo[m.n.1]alkanone cores possessing quaternary carbon centers adjacent to a bridged ketone represents a significant synthetic challenge. This type of architectural feature is embedded in various complex biologically active compounds such as hyperforin and garsubellin A. Herein, we report a highly diastereoselective one-pot Diels–Alder reaction/Au(I)-catalyzed carbocyclization to generate bicyclo[3.3.1]alkanones in yields ranging from 48–93%. PMID:21915201

Total synthesis of a CD-ring: side-chain building block for preparing 17-epi-calcitriol derivatives from the Hajos-Parrish dione.

PubMed

Michalak, Karol; Wicha, Jerzy

2011-08-19

An efficient synthesis of the key building block for 17-epi-calctriol from the Hajos-Parrish dione involving a sequence of diastereoselective transformation of the azulene core and the side-chain construction is presented.

Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base.

PubMed

Kawashima, Aki; Shu, Shuangjie; Takeda, Ryosuke; Kawamura, Akie; Sato, Tatsunori; Moriwaki, Hiroki; Wang, Jiang; Izawa, Kunisuke; Aceña, José Luis; Soloshonok, Vadim A; Liu, Hong

2016-04-01

Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2' alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.

An Expedient Regio- and Diastereoselective Synthesis of Hybrid Frameworks with Embedded Spiro[9,10]dihydroanthracene [9,3']-pyrrolidine and Spiro[oxindole-3,2'-pyrrolidine] Motifs via an Ionic Liquid-Mediated Multicomponent Reaction.

PubMed

Arumugam, Natarajan; Almansour, Abdulrahman I; Kumar, Raju Suresh; Menéndez, J Carlos; Sultan, Mujeeb A; Karama, Usama; Ghabbour, Hazem A; Fun, Hoong-Kun

2015-09-03

A series of hitherto unreported anthracene-embedded dispirooxindoles has been synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ from the reaction of isatin and sarcosine to 10-benzylideneanthracen-9(10H)-one as a dipolarophile in 1-butyl-3-methylimidazolium bromide([bmim]Br), an ionic liquid. This reaction proceeded regio- and diastereoselectively, in good to excellent yields.

Transition metal-catalyzed C-H activation reactions: diastereoselectivity and enantioselectivity.

PubMed

Giri, Ramesh; Shi, Bing-Feng; Engle, Keary M; Maugel, Nathan; Yu, Jin-Quan

2009-11-01

This critical review discusses historical and contemporary research in the field of transition metal-catalyzed carbon-hydrogen (C-H) bond activation through the lens of stereoselectivity. Research concerning both diastereoselectivity and enantioselectivity in C-H activation processes is examined, and the application of concepts in this area for the development of novel carbon-carbon and carbon-heteroatom bond-forming reactions is described. Throughout this review, an emphasis is placed on reactions that are (or may soon become) relevant in the realm of organic synthesis (221 references).

Iridium-Catalyzed Diastereoselective and Enantioselective Allylic Substitutions with Acyclic α-Alkoxy Ketones

DOE PAGES

Jiang, Xingyu; Chen, Wenyong; Hartwig, John F.

2016-04-01

The asymmetric alkylation of acyclic ketones is a longstanding challenge in organic synthesis. Here, are the diastereoselective and enantioselective allylic substitutions with acyclic α-alkoxy ketones catalyzed by a metallacyclic iridium complex to form products with contiguous stereogenic centers derived from the nucleophile and electrophile. These reactions occur between allyl methyl carbonates and unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones. The resulting products can be readily converted into enantioenriched tertiary alcohols and tetrahydrofuran derivatives without erosion of enantiomeric purity.

Iridium-Catalyzed Diastereoselective and Enantioselective Allylic Substitutions with Acyclic α-Alkoxy Ketones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Xingyu; Chen, Wenyong; Hartwig, John F.

The asymmetric alkylation of acyclic ketones is a longstanding challenge in organic synthesis. Here, are the diastereoselective and enantioselective allylic substitutions with acyclic α-alkoxy ketones catalyzed by a metallacyclic iridium complex to form products with contiguous stereogenic centers derived from the nucleophile and electrophile. These reactions occur between allyl methyl carbonates and unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones. The resulting products can be readily converted into enantioenriched tertiary alcohols and tetrahydrofuran derivatives without erosion of enantiomeric purity.

trans-2-Tritylcyclohexanol as a chiral auxiliary in permanganate-mediated oxidative cyclization of 2-methylenehept-5-enoates: application to the synthesis of trans-(+)-linalool oxide.

PubMed

Al Hazmi, Ali M; Sheikh, Nadeem S; Bataille, Carole J R; Al-Hadedi, Azzam A M; Watkin, Sam V; Luker, Tim J; Camp, Nicholas P; Brown, Richard C D

2014-10-03

The permanganate-mediated oxidative cyclization of a series of 2-methylenehept-5-eneoates bearing different chiral auxiliaries was investigated, leading to the discovery of trans-2-tritylcyclohexanol (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ∼97:3). Chiral resolution of (±)-TTC, prepared in one step from cyclohexene oxide, afforded (-)-(1S,2R)-TTC (er >99:1), which was applied to the synthesis of (+)-trans-(2S,5S)-linalool oxide.

Highly Enantioselective Synthesis of syn-β-Hydroxy α-Dibenzylamino Esters via DKR Asymmetric Transfer Hydrogenation and Gram-Scale Preparation of Droxidopa.

PubMed

Sun, Guodong; Zhou, Zihong; Luo, Zhonghua; Wang, Hailong; Chen, Lei; Xu, Yongbo; Li, Shun; Jian, Weilin; Zeng, Jiebin; Hu, Benquan; Han, Xiaodong; Lin, Yicao; Wang, Zhongqing

2017-08-18

A highly efficient preparation of enantiomerically pure syn aryl β-hydroxy α-dibenzylamino esters is reported. The outcome was achieved via dynamic kinetic resolution and asymmetric transfer hydrogenation of aryl α-dibenzylamino β-keto esters. The desired products were obtained in high yields (up to 98%) with excellent diastereoselectivity (>20:1 dr) and enantioselectivity (up to >99% ee). Furthermore, this method was applied for the gram-scale preparation of droxidopa.

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds.

PubMed

Day, Jonathan; McKeever-Abbas, Ben; Dowden, James

2016-05-04

Commercially available iron(III) and copper(I) complexes catalyzed multicomponent cycloaddition reactions between diazo compounds, pyridines, and electrophilic alkenes to give alkaloid-inspired tetrahydroindolizidines in high yield with high diastereoselectivity. Hitherto, the catalytic formation of versatile pyridinium ylides from metal carbenes has been poorly developed; the broad utility demonstrated herein sets the stage for the invention of further multicomponent reactions in future. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a Double Allylboration Reagent Targeting 1,5-syn-(E)-Diols: Application to the Synthesis of the C(23)-C(40) Fragment of Tetrafibricin

PubMed Central

Nuhant, Philippe; Kister, Jeremy; Lira, Ricardo; Sorg, Achim; Roush, William R.

2011-01-01

Interest in the synthesis of the C(23)-C(40) fragment 2 of tetrafibricin prompted us to develop a new method for the synthesis of 1,5-syn-(E)-diols. Toward this end, the kinetically controlled hydroboration of allenes 6, 33, ent-39, 42 and 45 with the Soderquist borane 25R were studied. Tetrabutylammonium allenyltrifluoroborate 45 gave superior results and was utilized in a double allylboration sequence with two different aldehydes to provide the targeted 1,5-syn-(E)-diols in generally high yields (72–98%), and with high enantioselectivity (>95% e.e.), diastereoselectivity (d.r. >20:1), and (E)/(Z) selectivity (>20:1). This new method was applied to the synthesis of the C(23)-C(40) fragment 2 of tetrafibricin. PMID:21857752

Diastereoselective addition of anisoles to N-tert-butanesulfinyl imines via four-membered lithium cycles.

PubMed

Reddy, Leleti Rajender; Kotturi, Sharadsrikar; Waman, Yogesh; Patel, Chirag; Patwa, Aditya; Shenoy, Rajesh

2018-06-06

A highly regio- and diastereo-selective ortho-lithiation/addition of anisoles to N-tert-butanesulfinyl imines resulting in the selective formation of chiral α-branched amines is described. This method is also efficient for highly regioselective benzylic lithiation of o-methylanisoles, followed by diastereoselective addition to N-tert-butanesulfinyl imines.

D-Glucosamine as a novel chiral auxiliary for the stereoselective synthesis of P-stereogenic phosphine oxides.

PubMed

D'Onofrio, A; Copey, L; Jean-Gérard, L; Goux-Henry, C; Pilet, G; Andrioletti, B; Framery, E

2015-09-14

D-Glucosamine was successfully employed as a chiral auxiliary for the enantioselective synthesis of phosphine oxides. The influence of the anomeric position was also investigated and revealed the excellent ability of the α-anomer to perform this transformation in a highly selective fashion. The methodology employed consisted of three steps: diastereoselective formation of the oxazaphospholidine followed by subsequent selective cleavage of P-N and P-O bonds by reaction with two Grignard reagents. P-epimers oxazaphospholidines were prepared switching from a P(v) to a P(III) precursor, thus allowing for the synthesis of enantiomeric phosphine oxides. In addition, the chiral auxiliary could be recovered and efficiently recycled.

Studies of asymmetric styrene cyclopropanation with a rhodium(II) metallopeptide catalyst developed with a high-throughput screen.

PubMed

Sambasivan, Ramya; Ball, Zachary T

2013-09-01

Dirhodium metallopeptides have been developed as selective catalysts for asymmetric cyclopropanation reactions. A selective ligand sequence has been identified by screening on-bead metallopeptide libraries in a 96-well plate format. Efficient ligand synthesis and screening allows a 200-member library to be created and assayed in less than three weeks. These metallopeptides catalyze efficient cyclopropanation of aryldiazoacetates, providing asymmetric access to cyclopropane products in high diastereoselectivity. © 2013 Wiley Periodicals, Inc.

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative.

PubMed

Yajima, Tomoko; Yoshida, Eriko; Hamano, Masako

2013-01-01

The cis- and trans-stereoselective radical additions to α-methylene-γ-alkyl- γ-lactams were investigated and the scope and limitation of the reaction were also revealed. This stereoselective radical reaction was used for synthesis of chiral pyroglutamic acid derivatives starting from a commercially available chiral amino acid.

A divergent [5+2] cascade approach to bicyclo[3.2.1]octanes: facile synthesis of ent-kaurene and cedrene-type skeletons.

PubMed

He, Chi; Bai, Zengbing; Hu, Jialei; Wang, Bingnan; Xie, Hujun; Yu, Lei; Ding, Hanfeng

2017-07-25

A solvent-dependent oxidative dearomatization-induced divergent [5+2] cascade approach to bicyclo[3.2.1]octanes was described. This novel protocol enables a facile synthesis of a series of diversely functionalized ent-kaurene and cedrene-type skeletons in good yields and excellent diastereoselectivities.

Divergent Synthesis of Multisubstituted Tetrahydrofurans and Pyrrolidines via Intramolecular Aldol-type Trapping of Onium Ylide Intermediates.

PubMed

Jing, Changcheng; Xing, Dong; Gao, Lixin; Li, Jia; Hu, Wenhao

2015-12-21

This paper reports a divergent strategy for the synthesis of multisubstituted tetrahydrofurans and pyrrolidines, starting from easily accessible β-hydroxyketones or β-aminoketones to react with diazo compounds. Under Rh(II) catalysis, this transformation is proposed to proceed through a metal-carbene-induced oxonium ylide or ammonium ylide formation followed by an intramolecular aldol-type trapping of these active intermediates. A series of highly substituted tetrahydrofurans and pyrrolidines are synthesized in high yields with good to excellent diastereoselectivities. Preliminary biological evaluations revealed that both types of heterocycles show good PTP1B inhibitory activities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-β-amino amides.

PubMed

Lin, Chao-Yang; Ma, Peng-Ju; Sun, Zhao; Lu, Chong-Dao; Xu, Yan-Jun

2016-01-18

A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-β-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-β-amino amides has been synthesized in high yields with excellent diastereoselectivities.

Enantioselective synthesis of chiral oxazolines from unactivated ketones and isocyanoacetate esters by synergistic silver/organocatalysis.

PubMed

Martínez-Pardo, Pablo; Blay, Gonzalo; Muñoz, M Carmen; Pedro, José R; Sanz-Marco, Amparo; Vila, Carlos

2018-03-15

A multicatalytic approach that combines a bifunctional Brønsted base-squaramide organocatalyst and Ag + as Lewis acid has been applied in the reaction of unactivated ketones with tert-butyl isocyanoacetate to give chiral oxazolines bearing a quaternary stereocenter. The formal [3+2] cycloaddition provided high yields of the corresponding cis-oxazolines with good diastereoselectivity and excellent enantioselectivity, being applied to aryl-alkyl and alkyl-alkyl ketones.

Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols.

PubMed

Ye, Chen-Xi; Melcamu, Yared Yohannes; Li, Heng-Hui; Cheng, Jiang-Tao; Zhang, Tian-Tian; Ruan, Yuan-Ping; Zheng, Xiao; Lu, Xin; Huang, Pei-Qiang

2018-01-29

Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman-Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N'-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).

Borohydride Reduction of Estrone: Demonstration of Diastereoselectivity in the Undergraduate Organic Chemistry Laboratory

ERIC Educational Resources Information Center

Aditya, Animesh; Nichols, David E.; Loudon, G. Marc

2008-01-01

This experiment presents a guided-inquiry approach to the demonstration of diastereoselectivity in an undergraduate organic chemistry laboratory. Chiral hindered ketones such as estrone, undergo facile reduction with sodium borohydride in a highly diastereoselective manner. The diastereomeric estradiols produced in the reaction can be analyzed and…

A Diastereoselective Intramolecular Pauson-Khand Approach to the Construction of the BC Ring System in Tuberostemoninol.

PubMed

Jia, Xiangna; Williams, Robert M

2008-12-12

Herein we describe an asymmetric approach to the synthesis of a BC-ring synthon in tuberostemoninol via an intramolecular Pauson-Khand reaction stereocontrolled by a commercially available chiral glycinate.

Concise, Stereocontrolled Synthesis of the Citrinadin B Core Architecture

PubMed Central

Guerrero, Carlos A.; Sorensen, Erik J.

2011-01-01

A concise, stereocontrolled synthesis of the citrinadin B core architecture from scalemic, readily available starting materials is disclosed. Highlights include ready access to both cyclic tryptophan tautomer and TRANS-2,6-disubstituted piperidine fragments, an efficient, stereoretentive mixed Claisen acylation for the coupling of these halves, and further diastereoselective carbonyl addition and oxidative rearrangement for assembly of the core. PMID:21894952

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

PubMed Central

Yoshida, Eriko; Hamano, Masako

2013-01-01

Summary The cis- and trans-stereoselective radical additions to α-methylene-γ-alkyl- γ-lactams were investigated and the scope and limitation of the reaction were also revealed. This stereoselective radical reaction was used for synthesis of chiral pyroglutamic acid derivatives starting from a commercially available chiral amino acid. PMID:23946839

Practical and Metal-Free Synthesis of Novel Enantiopure Amides Containing the Potentially Bioactive 5-Nitroimidazole Moiety.

PubMed

Spitz, Cédric; Mathias, Fanny; Giuglio-Tonolo, Alain Gamal; Terme, Thierry; Vanelle, Patrice

2016-11-04

We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1 H -imidazole to enantiomerically pure N - tert -butanesulfinimine. Then, the N - tert -butanesulfinyl-protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles.

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

PubMed Central

2015-01-01

Summary The conjugate addition reaction has been a useful tool in the formation of carbon–carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams. PMID:25977728

A Diastereoselective Intramolecular Pauson-Khand Approach to the Construction of the BC Ring System in Tuberostemoninol

PubMed Central

Jia, Xiangna; Williams, Robert M

2009-01-01

Herein we describe an asymmetric approach to the synthesis of a BC-ring synthon in tuberostemoninol via an intramolecular Pauson-Khand reaction stereocontrolled by a commercially available chiral glycinate. PMID:19779590

Diastereoselective Synthesis of (+/-)-1,2-Diphenyl-1,2-propanediol. A Discovery-Based Grignard Reaction Suitable for a Large Organic Lab Course

NASA Astrophysics Data System (ADS)

Ciaccio, James A.; Bravo, Roxana P.; Drahus, Antoinette L.; Biggins, John B.; Concepcion, Rosalyn V.; Cabrera, David

2001-04-01

We have developed an undergraduate organic laboratory experiment that probes the diastereoselectivity of the reaction between a Grignard reagent and a common, inexpensive a-chiral ketone. Students isolate a single diastereomer of (+/-)-1,2-diphenyl-1,2-propanediol by treatment of (+/-)-benzoin with MeMgI. Since the mp ranges of the two possible diol diastereomers differ by 10 °C, the reaction's diastereoselectivity can be established by mp determination alone, and it can be rationalized by the preferential addition of MeMgI to the least sterically hindered face of the carbonyl group in a rigid, five-membered cyclic intermediate (the "Cram chelate model"). This experiment is an interesting alternative to traditional Grignard experiments, is operationally straightforward and easily performed in large lab courses, and introduces students to p-facial discrimination by having them establish the stereochemical course of kinetically controlled nucleophilic addition to a carbonyl.

Total Synthesis of Spirotenuipesines A and B

PubMed Central

2008-01-01

Spirotenuipesines A and B, isolated from the entomopathogenic fungus Paecilomyces tenuipes by Oshima and co-workers, have been synthesized. The synthesis features the highly stereoselective construction of two vicinal all-carbon quaternary centers (C5 and C6) via an intramolecular cyclopropanation/radical initiated fragmentation sequence and a diastereoselective intermolecular Diels−Alder reaction between α-methylenelactone dienophile 20 and synergistic diene 6a. Installation of the C9 tertiary alcohol occurred via nucleophilic methylation. An RCM reaction to produce a tetrasubstituted double bond in the presence of free allylic alcohol and homoallylic oxygenated functional group is also described. This route shortened the synthesis of 11 from 9 steps to 3 steps. We have further developed a strategy to gain access to optically active spirotenuipesines A and B through the synthesis of enantioenriched 10 from commercially available R-(−)-epichlorohydrin. PMID:18973385

Synthesis of (±)-amathaspiramide F and discovery of an unusual stereocontrolling element for the [2,3]-Stevens rearrangement.

PubMed

Soheili, Arash; Tambar, Uttam K

2013-10-04

A formal total synthesis of (±)-amathaspiramide F through a tandem palladium-catalyzed allylic amination/[2,3]-Stevens rearrangement is reported. The unexpected diastereoselectivity of the [2,3]-Stevens rearrangement was controlled by the substitution patterns of an aromatic ring. This discovery represents a new stereocontrolling element for [2,3]-sigmatropic rearrangements in complex molecular settings.

Concise Stereocontrolled Formal Synthesis of (±)-Quinine and Total Synthesis of (±)-7-Hydroxyquinine via Merged Morita-Baylis-Hillman-Tsuji-Trost Cyclization

PubMed Central

Webber, Peter; Krische, Michael J.

2010-01-01

Concise stereoselective syntheses of (±)-quinine and (±)-7-hydroxyquinine are achieved using a catalytic enone cycloallylation that combines the nucleophilic features of the Morita-Baylis-Hillman reaction and the electrophilic features of the Tsuji-Trost reaction. Cyclization of enone-allyl carbonate 11 delivers the product of cycloallylation 13 in 68% yield. Diastereoselective conjugate reduction of the enone 13 (>20:1 dr) followed by exchange of N-protecting groups provides the saturated N-Boc-protected methyl ketone 19, which upon aldol dehydration provides quinoline containing enone 15, possessing all carbon atoms of quinine. Exposure of ketone 15 to L-selectride enables diastereoselective carbonyl reduction (>20:1 dr) to furnish the allylic alcohol 16. Stereoselective hydroxyl-directed epoxidation using an oxovanadium catalyst modified by N-hydroxy-N-Me-pivalamide delivers epoxide 17 (17:1 dr). Cyclization of the resulting amine-epoxide 17 provides (±)-7-hydroxyquinine in 13 steps and 11% overall yield from aminoacetaldehyde diethyl acetal. Notably, highly stereoselective formation of five contiguous stereocenters is achieved through a series of 1,2-asymmetric induction events. A formal synthesis of (±)-quinine is achieved upon deoxygenation of the N-Cbz-protected allylic acetate 22 to provide olefin 23, which previously has been converted to quinine. Thus, (±)-quinine is accessible in 16 steps and 4% overall yield from commercial aminoacetaldehyde diethyl acetal, making this route the most concise approach to quinine, to date. PMID:18989927

Synthesis of enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines and (2S,5R)-5-trifluoromethylproline.

PubMed

Lubin, Hodney; Pytkowicz, Julien; Chaume, Grégory; Sizun-Thomé, Gwenaëlle; Brigaud, Thierry

2015-03-06

Enantiopure trans-2,5-disubstituted trifluoromethylpyrrolidines were prepared on a several gram scale starting from a readily available chiral fluorinated oxazolidine (Fox). A pure oxazolopyrrolidine intermediate could be obtained after an efficient separation by selective diastereomer destruction. The addition of various Grignard reagents on this oxazolopyrrolidine provided disubstituted pyrrolidines with moderate to complete trans diastereoselectivity. The highly valuable compound (2S,5R)-5-trifluoromethylproline could be synthesized from the same oxazolopyrrolidine intermediate via a Strecker-type reaction.

Copper(II) carboxylate promoted intramolecular diamination of terminal alkenes: improved reaction conditions and expanded substrate scope.

PubMed

Zabawa, Thomas P; Chemler, Sherry R

2007-05-10

The copper(II) carboxylate promoted diamination reaction has been improved by the use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the less-polar solvent dichloroethane (DCE) to be used, and as a consequence, decomposition of less-reactive substrates could be avoided. High diastereoselectivity was observed in the synthesis of 2,5-disubstituted pyrrolidines. Ureas, bis(anilines), and alpha-amido pyrroles derived from 2-allylaniline could also participate in the diamination reaction.

Asymmetric synthesis of diacceptor cyclopropylphosphonates catalyzed by chiral Ru(II)-Pheox complexes

NASA Astrophysics Data System (ADS)

Chi, Le Thi Loan; Chanthamath, Soda; Shibatomi, Kazutaka; Iwasa, Seiji

2018-04-01

The first Ru(II)-catalyzed asymmetric cyclopropanation of diacceptor diazophosphonates with olefins is reported. The Ru(II)-Pheox complex 7e was found to be an efficient catalyst for the asymmetric cyclopropanation of α-cyano diazophosp honate with styrene under mild conditions to give the corresponding chiral diacceptor cyclopropylphosphonate products in high yields (up to 99%) with excellent diastereoselectivities (up to 99/1 dr). However, the enantioselectivity was difficult to control by the C1-symmetric catalyst (up to 68% ee).

Triple Nucleophilic Attack of Nitromethane on (2-Iminoaryl)divinyl Ketones: A Domino Synthetic Strategy for Hexahydrophenanthridinones.

PubMed

Feng, Chengjie; Li, Yifei; Xu, Qi; Pan, Ling; Liu, Qun; Xu, Xianxiu

2018-02-02

A novel domino reaction of (2-iminoaryl)divinyl ketones with nitromethane was developed for the efficient synthesis of hexahydrophenanthridin-9(5H)-ones. The reaction proceeded smoothly from readily available starting materials under mild reaction conditions to construct three new bonds and two rings with high diastereoselectivities in good to excellent yields in a single step. A mechanism is proposed, involving a stepwise double Michael addition/aza-Henry reaction cascade, and in this transformation, nitromethane acts as a trinucleophile.

A Rapid, One-Pot Synthesis of β-Siloxy-α-Haloaldehydes

PubMed Central

Saadi, Jakub; Akakura, Matsujiro

2011-01-01

The Mukaiyama cross aldol reaction of α-fluoro-, α-chloro-, and α-bromoacetaldehyde-derived (Z)-tris(trimethylsilyl)- silyl enol ethers furnishing anti-β-siloxy-α-haloaldehydes is described. A highly diastereoselective, one-pot, sequential double aldol process, affording novel β,δ-bissiloxy-α,γ-bishaloaldehydes is developed. Reactions are catalyzed by C6F5CHTf2 and C6F5CTf2AlMe2 (0.5–1.5 mol%) and provide access to halogenated polyketide fragments. PMID:21815682

Dinuclear Zinc-Prophenol-Catalyzed Enantioselective α-Hydroxyacetate Aldol Reaction with Activated Ester Equivalents

PubMed Central

Trost, Barry M.; Michaelis, David J.; Truica, Mihai I.

2013-01-01

An enantioselective α-hydroxyacetate aldol reaction that employs N-acetyl pyrroles as activated ester equivalents and generates syn 1,2-diols in good yield and diastereoselectivity is reported. This dinuclear zinc Prophenol-catalyzed transformation proceeds with high enantioselectivity with a wide variety of substrates including aryl, alyl, and alkenyl aldehydes. The resulting α,β-dihydroxy activated esters are versatile intermediates for the synthesis of a variety of carboxylic acid derivatives including amides, esters, and unsymmetrical ketones. PMID:23947595

Total synthesis of the proposed structure of trichodermatide A.

PubMed

Myers, Eddie; Herrero-Gómez, Elena; Albrecht, Irina; Lachs, Jennifer; Mayer, Peter; Hanni, Matti; Ochsenfeld, Christian; Trauner, Dirk

2014-10-17

A short total synthesis of the published structure of racemic trichodermatide A is reported. Our synthesis involves a Knoevenagel condensation/Michael addition sequence, followed by the formation of tricyclic hexahydroxanthene-dione and a diastereoselective bis-hydroxylation. The final product, the structure of which was confirmed by X-ray crystallography, has NMR spectra that are very similar, but not identical, to those of the isolated natural product. Quantum chemically computed (13)C shifts agree well with the present NMR measurements.

Synthesis of diazatricyclic core of Madangamines from cis-perhydroisoquinolines.

PubMed

Quirante, Josefina; Paloma, Laura; Diaba, Faïza; Vila, Xavier; Bonjoch, Josep

2008-01-18

Synthesis of the tricyclic core of madangamine alkaloids has been achieved in a 10-step sequence starting from a 4-(aminomethyl)anisole derivative. A Birch reduction and acylation with cyanoacetic acid followed by an intramolecular Michael process renders a polyfunctionalized cis-perhydroisoquinoline. A diastereoselective allylation and reduction of amide, nitrile, and ketone groups leads to a bicyclic alcohol, which undergoes aminocyclization through the nosyl derivative to the diazatricyclic ring.

Catalytic diastereo- and enantioselective additions of versatile allyl groups to N-H ketimines

NASA Astrophysics Data System (ADS)

Jang, Hwanjong; Romiti, Filippo; Torker, Sebastian; Hoveyda, Amir H.

2017-12-01

There are many biologically active organic molecules that contain one or more nitrogen-containing moieties, and broadly applicable and efficient catalytic transformations that deliver them diastereoselectively and/or enantioselectively are much sought after. Various methods for enantioselective synthesis of α-secondary amines are available (for example, from additions to protected/activated aldimines), but those involving ketimines are much less common. There are no reported additions of carbon-based nucleophiles to unprotected/unactivated (or N-H) ketimines. Here, we report a catalytic, diastereo- and enantioselective three-component strategy for merging an N-H ketimine, a monosubstituted allene and B2(pin)2, affording products in up to 95% yield, >98% diastereoselectivity and >99:1 enantiomeric ratio. The utility of the approach is highlighted by synthesis of the tricyclic core of a class of compounds that have been shown to possess anti-Alzheimer activity. Stereochemical models developed with the aid of density functional theory calculations, which account for the observed trends and levels of enantioselectivity, are presented.

Approaches to the Chemical Synthesis of the Chlorosulfolipids

PubMed Central

Chung, Won-Jin; Vanderwal, Christopher D.

2014-01-01

CONSPECTUS Since the initial discovery of the chlorosulfolipids in 1969, the chemical synthesis community largely ignored these compounds for nearly four decades, perhaps because they contain a high density of chlorine atoms that suggested that these molecules and any projected synthetic intermediates might be unstable. Beginning in 2008, a sudden flurry of synthesis activity by several research groups, including our own, appeared in the literature. In this Account, we highlight our work from the last several years on the chemical synthesis of the chlorosulfolipids. Our work in this area began with attempts to stereoselectively generate the abundant dichloroalcohol functional group arrangements in these natural targets. In these early studies, we learned that many polychlorinated intermediates were far more stable than anticipated. We also developed a method for the diastereoselective dichlorination of allylic alcohol derivatives that permitted access to the syn,syn-dichloroalcohol stereotriad found in several chlorosulfolipids. Concurrently, we investigated an approach to mytilipin A that included multiple intermediates bearing β-chloroaldehyde functional group arrangements, but this route proved intractable. However, we leveraged what we had learned from this approach into our first success in this area: we synthesized danicalipin A via a route that introduced all of the polar functional groups using alkene oxidation reactions. By adapting this relatively general strategy, we completed an enantioselective synthesis of malhamensilipin A. This body of work also resulted in the full stereochemical elucidation of danicalipin A and the structural revision of malhamensilipin A. Finally, with the advent of Z-selective alkene cross metathesis, we developed a second-generation synthesis that featured this strategy in place of a poorly performing Wittig olefination that plagued our first approach. In addition to this new convergent step, we developed a reliable protocol for diastereoselective addition to highly sensitive α,β-dichloroaldehydes and a method for kinetic resolution of complex vinyl epoxides. Altogether, these advances led to a synthesis of enantioenriched mytilipin A in only eight steps. In the context of this work, we discovered a number of highly stereoselective reactions that might offer new, broadly applicable lessons in acyclic stereocontrol. Moreover, this research testifies to the stability of polychlorinated molecules and should inspire confidence in the use of aliphatic chlorides in other applications, including in discovery chemistry. PMID:24400674

Chiral-catalyst-based convergent synthesis of HIV protease inhibitor GRL-06579A.

PubMed

Mihara, Hisashi; Sohtome, Yoshihiro; Matsunaga, Shigeki; Shibasaki, Masakatsu

2008-02-01

Catalytic asymmetric synthesis of GRL-06579A (1), an HIV-1 protease inhibitor effective against multi-protease-inhibitor-resistant viruses, is described. A convergent strategy that utilizes heterobimetallic multifunctional catalysts developed in our group is a key feature of the synthesis. The chirality of the bicyclic tetrahydrofuran unit of 1 was introduced through Al-Li-bis(binaphthoxide) (ALB) catalyst-controlled Michael addition of dimethyl malonate to racemic 4-O-protected cyclopentenone. ALB afforded not only the trans adduct with up to 96% ee from a matched substrate through kinetic resolution, but also the cis adduct with 99% ee through a catalyst-controlled Michael addition to a mismatched substrate. The Michael addition to produce the unusual cis adduct is described in detail. The framework of the bicyclic tetrahydrofuran was constructed by an intramolecular oxy-Michael reaction. The amino alcohol unit was constructed by an La-Li3-tris(binaphthoxide) (LLB)-catalyzed diastereoselective nitroaldol reaction of N-Boc aldehyde (Boc = tert-butoxycarbonyl) derived from L-phenylalanine. LLB promoted the nitroaldol reaction without racemization of the chiral aldehyde to give the nitroaldol adduct in 85% yield and with 93:7 diastereoselectivity and over 99% ee.

Synthesis of cis- and trans-α-l-[4.3.0]bicyclo-DNA monomers for antisense technology: methods for the diastereoselective formation of bicyclic nucleosides.

PubMed

Hanessian, Stephen; Schroeder, Benjamin R; Merner, Bradley L; Chen, Bin; Swayze, Eric E; Seth, Punit P

2013-09-20

Two α-L-ribo-configured bicyclic nucleic acid modifications, represented by analogues 12 and 13, which are epimeric at C3' and C5' have been synthesized using a carbohydrate-based approach to build the bicyclic core structure. An intramolecular L-proline-mediated aldol reaction was employed to generate the cis-configured ring junction of analogue 12 and represents a rare application of this venerable organocatalytic reaction to a carbohydrate system. In the case of analogue 13, where a trans-ring junction was desired, an intermolecular diastereoselective Grignard reaction followed by ring-closing metathesis was used. In order to set the desired stereochemistry at the C5' positions of both nucleoside targets, a study of diastereoselective Lewis acid mediated allylation reactions on a common bicyclic aldehyde precursor was carried out. Analogue 12 was incorporated in oligonucleotide sequences, and thermal denaturation experiments indicate that it is destabilizing when paired with complementary DNA and RNA. However, this construct shows a significant improvement in nuclease stability relative to a DNA oligonucleotide.

Diastereoselective synthesis of chiral 1,3-cyclohexadienals

PubMed Central

de la Granja, Ángela P.; Capitán, M. Carmen; Moro, R. F.; Marcos, Isidro S.; Garrido, Narciso M.; Sanz, Francisca; Calle, Emilio

2018-01-01

A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different β-disubstituted-α,β-unsaturated aldehydes with a chiral α,β-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner. PMID:29438416

Diastereoselective synthesis of chiral 1,3-cyclohexadienals.

PubMed

Urosa, Aitor; Tobal, Ignacio E; de la Granja, Ángela P; Capitán, M Carmen; Moro, R F; Marcos, Isidro S; Garrido, Narciso M; Sanz, Francisca; Calle, Emilio; Díez, David

2018-01-01

A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different β-disubstituted-α,β-unsaturated aldehydes with a chiral α,β-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner.

General Catalytic Enantioselective Access to Monohalomethyl and Trifluoromethyl Cyclopropanes.

PubMed

Huang, Wei-Sheng; Schlinquer, Claire; Poisson, Thomas; Pannecoucke, Xavier; Charette, André B; Jubault, Philippe

2018-05-29

An efficient catalytic enantioselective access to chiral functionalized trifluoromethyl cyclopropanes from two classes of diazo compounds and alpha-trifluoromethyl styrenes using Rh2((S)-BTPCP)4 as a catalyst is described. This method provides an efficient and practical strategy for the synthesis of highly functionalized CF3-cyclopropanes with excellent diastereoselectivities (up to 20:1) and enantioselectivities (up to 99% ee). The depicted methodology represents up to date the most efficient catalytic enantioselective method to access highly decorated chiral CF3-cyclopropanes. Extension to chiral monohalomethyl cyclopropanes in high ee is also reported. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective synthesis of anti-β-hydroxy-α-amido esters via transfer hydrogenation.

PubMed

Seashore-Ludlow, Brinton; Villo, Piret; Häcker, Christine; Somfai, Peter

2010-11-19

The asymmetric transfer hydrogenation of α-amido-β-keto esters to provide the corresponding anti-β-hydroxy-α-amido esters in good to excellent yields, diastereoselectivity, and enantioselectivity is reported. The procedure is operationally simple, and delicate handling of the catalyst is not necessary.

Stereoselective Synthesis of Morpholines Via Copper-Promoted Oxyamination of Alkenes

PubMed Central

Sequeira, Fatima C.

2012-01-01

A new copper(II) 2-ethylhexanoate promoted addition of an alcohol and an amine across an alkene (oxyamination) is reported. The alcohol addition is intramolecular while coupling with the amine occurs intermolecularly. Several 2-aminomethyl morpholines were synthesized in good to excellent yields and diastereoselectivities. PMID:22894680

Stereoselective isoxazolidine synthesis via copper-catalyzed alkene aminooxygenation.

PubMed

Karyakarte, Shuklendu D; Smith, Thomas P; Chemler, Sherry R

2012-09-07

Isoxazolidines are useful in organic synthesis, drug discovery, and chemical biology endeavors. A new stereoselective synthesis of methyleneoxy-substituted isoxazolidines is disclosed. The method involves copper-catalyzed aminooxygenation/cyclization of N-sulfonyl-O-butenyl hydroxylamines in the presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl radical (TEMPO) and O(2) and provides substituted isoxazolidines in excellent yields and diastereoselectivities. We also demonstrate selective mono N-O reduction followed by oxidation of the remaining N-O bond to reveal a 2-amino-γ-lactone. Reduction of the γ-lactone reveals the corresponding aminodiol.

Copper(II) Carboxylate Promoted Intramolecular Diamination of Terminal Alkenes: Improved Reaction Conditions and Expanded Substrate Scope

PubMed Central

Zabawa, Thomas P.

2008-01-01

The copper(II) carboxylate promoted diamination reaction has been improved by the use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the less polar solvent, dichloroethane (DCE) to be used, and as a consequence, decomposition of less reactive substrates could be avoided. High diastereoselectivity was observed in the synthesis of 2,5-disubstituted pyrrolidines. Ureas, bis(anilines) and α-amido pyrroles derived from 2-allylaniline could also participate in the diamination reaction. PMID:17447781

Highly efficient and generalized asymmetric synthesis of quaternary stereogenic carbon-containing β-amino indanones/indanoles via Mannich-type additions between 1-indanones and N-tert-butanesulfinylketimines.

PubMed

Wu, Lingmin; Xie, Chen; Mei, Haibo; Soloshonok, Vadim A; Han, Jianlin; Pan, Yi

2014-07-14

Here we report that, unlike other ketones, 1-indanone and acetophenone derived enolates undergo Mannich-type addition reactions with N-tert-butanesulfinyl ketimines with excellent yields (up to 98%) and diastereoselectivity (>99/1). The resulting compounds represent a new type of biologically relevant β-aminoketone derivative bearing quaternary stereogenic carbon, which could be further converted into the corresponding β-amino ketones and β-amino alcohols, possessing three consecutive stereogenic centres.

Synthesis and biological activity of pyrrole analogues of combretastatin A-4.

PubMed

Jung, Eun-Kyung; Leung, Euphemia; Barker, David

2016-07-01

A series of pyrrole analogues of combretastatin (CA-4) were synthesized and tested for their anti-proliferative activity. The highly diastereoselective acyl-Claisen rearrangement was used to provide 2,3-syn disubstituted morpholine amides which were used as precursors for the various analogues. This synthesis allows for the preparation of 1,2- and 2,3-diaryl-1H-pyrroles which are both geometrically similar to CA-4. These pyrrolic analogues were tested for their anti-proliferative activity against two human cell lines, K562 and MDA-MB-231 with 2,3-diaryl-1H-pyrrole 35 exhibiting the most potent activity with IC50 value of 0.07μM against MDA-MB-231 cell line. Copyright © 2016 Elsevier Ltd. All rights reserved.

A stereoselective, catalytic strategy for the in-flow synthesis of advanced precursors of rasagiline and tamsulosin.

PubMed

Brenna, Davide; Pirola, Margherita; Raimondi, Laura; Burke, Anthony J; Benaglia, Maurizio

2017-12-01

The diastereoselective, trichlorosilane-mediate reduction of imines, bearing different and removable chiral auxiliaries, in combination either with achiral bases or catalytic amounts of chiral Lewis bases, was investigated to afford immediate precursors of chiral APIs (Active Pharmaceutical Ingredients). The carbon-nitrogen double bond reduction was successfully performed in batch and in flow mode, in high yields and almost complete stereocontrol. By this metal-free approach, the formal synthesis of rasagiline and tamsulosin was successfully accomplished in micro(meso) flow reactors, under continuous flow conditions. The results of these explorative studies represent a new, important step towards the development of automated processes for the preparation of enantiopure biologically active compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crystallization-induced dynamic resolution of Fox chiral auxiliary and application to the diastereoselective electrophilic fluorination of amide enolates.

PubMed

Lubin, Hodney; Dupuis, Christophe; Pytkowicz, Julien; Brigaud, Thierry

2013-04-05

A highly efficient crystallization-induced dynamic resolution (CIDR) of trans-Fox (fluorinated oxazolidine) chiral auxiliary is reported. This chiral auxiliary was used for highly diastereoselective (>98% de) electrophilic fluorination of amide enolates. After removal of the chiral auxiliary, highly valuable enantiopure α-fluorocarboxylic acids and β-fluoroalcohols are obtained.

A practical synthesis of (+)-biotin from L-cysteine.

PubMed

Seki, Masahiko; Hatsuda, Masanori; Mori, Yoshikazu; Yoshida, Shin-ichi; Yamada, Shin-ichi; Shimizu, Toshiaki

2004-11-19

Alpha-amino aldehyde 4, which is readily derived from L-cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16, afforded alpha-amino nitrile 5 with high diastereoselectivity (syn/anti=11:1) and in high yield. Amide 6, derived from 5, was converted to thiolactone 8, a key intermediate in the synthesis of (+)-biotin (1), by a novel S,N-carbonyl migration and cyclization reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21, which has an ester group, in the presence of a heterogeneous Pd/C catalyst allowed the efficient installation of the 4-carboxybutyl chain to provide 9. Compound 9 was hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34 % overall yield from L-cysteine.

Arene-chromium tricarbonyl complexes in the Pauson-Khand reaction.

PubMed

Rosillo, Marta; Domínguez, Gema; Casarrubios, Luis; Pérez-Castells, Javier

2005-12-09

[reactions: see text] We show the use of arene-chromium tricarbonyl complexes in intra- and intermolecular Pauson-Khand reactions. Both styrene and ethynylbenzene complexes react with alkynes and olefins. The synthesis of enynes connected through chromium-complexed aromatic rings is developed. The intramolecular Pauson-Khand reaction occurs in a totally diastereoselective manner.

Highly chemo- and enantioselective cross-benzoin reaction of aliphatic aldehydes and α-ketoesters.

PubMed

Thai, Karen; Langdon, Steven M; Bilodeau, François; Gravel, Michel

2013-05-03

An electron-deficient, valine-derived triazolium salt is shown to catalyze a highly chemo- and enantioselective cross-benzoin reaction between aliphatic aldehydes and α-ketoesters. This methodology represents the first high yielding and highly enantioselective intermolecular cross-benzoin reaction using an organocatalyst (up to 94% ee). Further diastereoselective reduction of the products gives access to densely oxygenated compounds with high chemo- and diastereoselectivity.

Enantioselective Rhodium-Catalyzed Dimerization of ω-Allenyl Carboxylic Acids: Straightforward Synthesis of C2 -Symmetric Macrodiolides.

PubMed

Steib, Philip; Breit, Bernhard

2018-04-19

Herein, we report on the first enantioselective and atom-efficient catalytic one-step dimerization method to selectively transform ω-allenyl carboxylic acids into C 2 -symmetric 14- to 28-membered bismacrolactones (macrodiolides). This convenient asymmetric access serves as an attractive route towards multiple naturally occuring homodimeric macrocyclic scaffolds and demonstrates excellent efficiency to construct the complex, symmetric core structures. By utilizing a rhodium catalyst with a modified chiral cyclopentylidene-diop ligand, the desired diolides were obtained in good to high yields, high diastereoselectivity, and excellent enantioselectivity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stereoselective Synthesis of Functionalized Bicyclic Scaffolds by Passerini 3-Center-2-Component Reactions of Cyclic Ketoacids.

PubMed

Cioc, Răzvan C; Estévez, Verónica; van der Niet, Daan J; Vande Velde, Christophe M L; Turrini, Nikolaus G; Hall, Mélanie; Faber, Kurt; Ruijter, Eelco; Orru, Romano V A

2017-03-03

We report the use of bifunctional starting materials (ketoacids) in a diastereoselective Passerini three-center-two-component reaction. Study of the reaction scope revealed the required structural features for stereoselectivity in the isocyanide addition. In this system, an interesting isomerization of the primary Passerini product - the α-carboxamido lactone - into an atypical product, an α-hydroxy imide, was found to occur under acidic conditions. Furthermore, enantioenriched Passerini products can be generated from an enantioenriched ketoacid obtained by chemoenzymatic synthesis.

Tetramethylnorbornadiene, a versatile alkene for cyclopentenone synthesis through intermolecular Pauson-Khand reactions.

PubMed

Revés, Marc; Lledó, Agustí; Ji, Yining; Blasi, Emma; Riera, Antoni; Verdaguer, Xavier

2012-07-06

1,2,3,4-Tetramethyl-bicyclo[2.2.1]hepta-2,5-diene (TMNBD, for tetramethylnorbornadiene) has been prepared and used successfully as an acetylene equivalent in the synthesis of substituted cyclopentenones. TMNBD is easily accessible on a multigram scale and displays excellent reactivity toward the intermolecular Pauson-Khand reaction. Conjugate additions on the resulting tricyclic compounds proceed with exquisite diastereoselectivity. The retro-Diels-Alder reaction of these TMNBD derivatives occurs under much smoother conditions than those required for its norbornadiene homologues.

Highly diastereoselective reductive coupling of 2-bromo-2,3,3,3-tetrafluoropropanamide with aldehydes promoted by triphenylphosphine-titanium(IV) isopropoxide. An efficient route to the synthesis of erythro-alpha-fluoro-alpha-(trifluoromethyl)-beta-hydroxy amides.

PubMed

Sato, Kei; Sekiguchi, Takashi; Ishihara, Takashi; Konno, Tsutomu; Yamanaka, Hiroki

2004-07-23

The reductive coupling reaction of N-methoxy-N-methyl-2-bromo-2,3,3,3-tetrafluoropropanamide (Weinreb amide) with various aldehydes under the influence of the combined reagent, 1.2 equiv each of triphenylphosphine and titanium(IV) isopropoxide, took place smoothly at ambient temperature to give the corresponding alpha-fluoro-alpha-(trifluoromethyl)-beta-hydroxy amides in a highly erythro-selective manner. The high erythro selectivity was also obtained even by employing a combination of triphenylphosphine (1.2 equiv) and a catalytic amount of titanium(IV) isopropoxide.

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.

Ni(ClO4)(2)-catalysed regio- and diastereoselective [3+2] cycloaddition of indoles and aryl oxiranyl-dicarboxylates/diketones: a facile access to furo[3,4-b]indoles.

PubMed

Zhang, Jieming; Chen, Zuliang; Wu, Hai-Hong; Zhang, Junliang

2012-02-07

Ni(ClO(4))(2)·6H(2)O-catalysed regioselective and diastereoselective [3+2]-annulations of aryl oxiranyl-dicarboxylates and indoles via selective C-C bond cleavage of oxirane were revealed. The cycloadditions proceed smoothly with high regio- and diastereoselectivity under mild conditions leading to 1H-furo[3,4-b]indoles in good to excellent yields. This journal is © The Royal Society of Chemistry 2012

Direct catalytic asymmetric aldol-Tishchenko reaction.

PubMed

Gnanadesikan, Vijay; Horiuchi, Yoshihiro; Ohshima, Takashi; Shibasaki, Masakatsu

2004-06-30

A direct catalytic asymmetric aldol reaction of propionate equivalent was achieved via the aldol-Tishchenko reaction. Coupling an irreversible Tishchenko reaction to a reversible aldol reaction overcame the retro-aldol reaction problem and thereby afforded the products in high enantio and diastereoselectivity using 10 mol % of the asymmetric catalyst. A variety of ketones and aldehydes, including propyl and butyl ketones, were coupled efficiently, yielding the corresponding aldol-Tishchenko products in up to 96% yield and 95% ee. Diastereoselectivity was generally below the detection limit of 1H NMR (>98:2). Preliminary studies performed to clarify the mechanism revealed that the aldol products were racemic with no diastereoselectivity. On the other hand, the Tishchenko products were obtained in a highly enantiocontrolled manner.

Catalytic Stereoselective Installation of Boron Via C-C Bond Formation and Stereoselective Synthesis of N-Heterocyclic Scaffolds Via Main Group Lewis Acid Catalysis

NASA Astrophysics Data System (ADS)

Moyer, Brandon S.

CATALYTIC STEREOSELECTIVE INSTALLATION OF BORON VIA C-C BOND FORMATION. Enantiomerically pure chiral boron-containing molecules provide enabling platforms for chemical synthesis in that they are configurationally stable, they function as useful synthons for various functional groups, and their transformations into those diverse functionalities are stereospecific. With consensus that chiral alkyl sp3 C-B bond-containing compounds are desirable building blocks, and given that most enantioselective preparations to date focus on installing a stereodefined C-B bond, our group sought to develop catalytic methods to generate and use chiral alpha-boron-containing nucleophiles that would enable the direct formation of a new C-C bond. To this extent, we exploited the utility of alkyl 1,1-diboron reagents, which have been shown to readily undergo facile activation and transmetalation in the presence of alkoxide bases to form chiral alpha-boryl nucleophiles. The result of these investigations was the development of the first catalytic enantio- and diastereoselective synthesis of syn-1,2-hydroxyboronates via addition to aldehydes (Ch. 1). The reactions are promoted by a readily available chiral monodentate phosphoramidite-Cu(I) complex in the presence of an alkyl 1,1-diboron reagent. The products contain two contiguous stereogenic centers and are obtained in up to 91% yield, >98:2 d.r., and 98:2 e.r. The reaction is tolerant of aryl and vinyl aldehydes, and the 1,2-hydroxyboronate products can be transformed into versatile derivatives. Mechanistic experiments indicate that control of absolute stereochemistry resides at the alpha-boryl component. Further investigations resulted in the development of a substantially more reactive Ag(I) catalytic protocol for the diastereoselective synthesis of complementary anti-1,2-hydroxyboronates with up to 99:1 d.r. (Ch. 2). We found that the increased reactivity of Ag(I), in conjunction with stoichiometric KOtBu, allowed for a substantial broadening of substituted 1,1-diboronates that participate in the reaction. In addition, alkyl aldehydes were found to be suitable electrophiles with n-BuLi as an activator. STEREOSELECTIVE SYNTHESIS OF N-HETEROCYCLIC SCAFFOLDS VIA MAIN GROUP LEWIS ACID CATALYSIS. Silylium ions (formally [R 3Si]+) have long been the subject of investigations and significant debate in both theoretical and experimental chemistry, but few catalytic, synthetic applications have been reported due to the exceptionally high reactivity and Lewis acidity of these elusive species. Chapter 3 discusses the application of easily accessible silylium ion catalysts to the stereoselective synthesis of various N-heterocyclic pyrrolidine and piperidine scaffolds. The tested substrates are derived from the chiral pool and can be obtained in three high-yielding steps from amino alcohols; subsequent stereoselective silylium ion-catalyzed Prins-cyclization and trapping with R3Si-Nu nucleophiles (e.g. Nu = H, allyl, azide, and enol ethers) results in novel nitrogen-containing polycyclic scaffolds with potential medicinal chemistry applications. An appendix to this chapter (A) discusses the substrate scope of the unpublished discovery that the Lewis acid B(C6F5)3 catalyzes a stereospecific Prins cyclization followed by an elimination (formally a carbonyl-ene reaction) to form trans-tetrahydropyridine products in exceptionally high yield and diastereoselectivity.

Asymmetric conjugate addition of Grignard reagents to 3-silyl unsaturated esters for the facile preparation of enantioenriched β-silylcarbonyl compounds and allylic silanes.

PubMed

Zhao, Kai; Loh, Teck-Peng

2014-12-08

A highly enantioselective conjugate addition of Grignard reagents to 3-silyl unsaturated esters to deliver synthetically useful chiral β-silylcarbonyl compounds was developed. The synthetic value of this methodology was further illustrated by the synthesis of enantioenriched β-hydroxyl esters and the facile access granted to various α-chiral allylic silanes. A plethora of diastereoselective transformations of β-silylenolates were also investigated and afforded manifold organosilanes that contained contiguous stereogenic centers with excellent enantioselectivity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stereoselective synthesis of functionalized cyclic amino acid derivatives via a [2,3]-Stevens rearrangement and ring-closing metathesis.

PubMed

Nash, Aaron; Soheili, Arash; Tambar, Uttam K

2013-09-20

Unnatural cyclic amino acids are valuable tools in biomedical research and drug discovery. A two-step stereoselective strategy for converting simple glycine-derived aminoesters into unnatural cyclic amino acid derivatives has been developed. The process includes a palladium-catalyzed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalyzed ring-closing metathesis. The [2,3]-rearrangement proceeds with high diastereoselectivity through an exo transition state. Oppolzer's chiral auxiliary was utilized to access an enantiopure cyclic amino acid by this approach, which will enable future biological applications.

IBX-mediated oxidation of unactivated cyclic amines: application in highly diastereoselective oxidative Ugi-type and aza-Friedel-Crafts reactions.

PubMed

de Graaff, C; Bensch, L; van Lint, Matthijs J; Ruijter, E; Orru, R V A

2015-10-28

The first o-iodoxybenzoic acid (IBX) mediated oxidation of unactivated amines to imines is described. A range of meso-pyrrolidines were shown to be suitable substrates. The chemical space was further explored with one-pot oxidative Ugi-type and aza-Friedel-Crafts reactions, which proved to be highly diastereoselective.

De novo asymmetric synthesis and biological analysis of the daumone pheromones in Caenorhabditis elegans and in the soybean cyst nematode Heterodera glycines

USDA-ARS?s Scientific Manuscript database

The de novo asymmetric total syntheses of daumone 1, daumone 2 and analogs are described. The key steps of our approach are the diastereoselective palladium catalyzed glycosylation reaction, the Noyori reduction of a acetylfuran and a propargyl ketone, which introduce the absolute stereochemistry of...

Synthesis of β-C-Glycopyranosyl Aldehydes and 2,6-Anhydro-heptitols.

PubMed

Khatri, Vinod; Kumar, Amit; Singh, Balram; Malhotra, Shashwat; Prasad, Ashok K

2015-11-06

A convenient route has been developed for the diastereoselective synthesis of β-C-glycopyranosyl aldehydes from D-glucose, D-mannose, and D-galactose. The key step in the synthesis of C-glycosyl aldehydes is the aryl driven reductive dehydration on 1-phenyl-2-(2',3',4',6'-tetra-O-acetyl-β-D-glycopyranosyl)ethanone to afford alkenes, which on oxidation afford the desired compounds in good yield. β-C-Glycopyranosyl aldehydes have been converted to 2,6-anhydro-heptitols in quantitative yields. The 2,6-anhydro-heptitols derived from D-mannose and D-galactose are enantiomeric and are useful linkers for the synthesis of macrocycles/amphiphiles of complementary chirality.

Computationally designed and experimentally confirmed diastereoselective rhodium-catalyzed Pauson-Khand reaction at room temperature.

PubMed

Baik, Mu-Hyun; Mazumder, Shivnath; Ricci, Paolo; Sawyer, James R; Song, Ye-Geun; Wang, Huijun; Evans, P Andrew

2011-05-25

The computational analysis of the rhodium-catalyzed Pauson-Khand reaction indicates that the key transition state is highly charge-polarized, wherein different diastereoisomers have distinctively different charge polarization patterns. Experimental studies demonstrate that chloro-enynes provide the optimal σ-electron-withdrawing group to promote polarization and thereby reduce the activation barrier to provide a highly diastereoselective reaction at room temperature.

Synthesis of the Strychnos Alkaloid (-)-Strychnopivotine and Confirmation of its Absolute Configuration.

PubMed

Maertens, Gaëtan; Canesi, Sylvain

2016-05-17

The first enantioselective synthesis of (-)-strychnopivotine from a known and inexpensive phenol has been achieved in 15 steps. The strategy is based on a new diastereoselective aza-Michael-enol-ether cascade desymmetrization of a dienone, guided by a removable lactic acid-derived chiral auxiliary. Synthesis involves a phenol dearomatization, a conjugated silicon addition, a stereoselective double reductive amination, and two Heck-type carbopalladations as key steps. The absolute configuration of the natural compound, which, to date, has been uncertain, was confirmed by using circular dichroism (CD) spectroscopy and X-ray analyses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid Construction of a Benzo-Fused Indoxamycin Core Enabled by Site-Selective C-H Functionalizations.

PubMed

Bedell, T Aaron; Hone, Graham A B; Valette, Damien; Yu, Jin-Quan; Davies, Huw M L; Sorensen, Erik J

2016-07-11

Methods for functionalizing carbon-hydrogen bonds are featured in a new synthesis of the tricyclic core architecture that characterizes the indoxamycin family of secondary metabolites. A unique collaboration between three laboratories has engendered a design for synthesis featuring two sequential C-H functionalization reactions, namely a diastereoselective dirhodium carbene insertion followed by an ester-directed oxidative Heck cyclization, to rapidly assemble the congested tricyclic core of the indoxamycins. This project exemplifies how multi-laboratory collaborations can foster conceptually novel approaches to challenging problems in chemical synthesis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

PubMed Central

Sallio, Romain; Lebrun, Stéphane; Capet, Frédéric; Agbossou-Niedercorn, Francine

2018-01-01

A new asymmetric organocatalyzed intramolecular aza-Michael reaction by means of both a chiral auxiliary and a catalyst for stereocontrol is reported for the synthesis of optically active isoindolinones. A selected cinchoninium salt was used as phase-transfer catalyst in combination with a chiral nucleophile, a Michael acceptor and a base to provide 3-substituted isoindolinones in good yields and diastereomeric excesses. This methodology was applied to the asymmetric synthesis of a new pazinaclone analogue which is of interest in the field of benzodiazepine-receptor agonists. PMID:29623121

Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

NASA Astrophysics Data System (ADS)

Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

2015-08-01

The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

Catalyst-Directed Diastereoselective Isomerization of Allylic Alcohols for the Stereoselective Construction of C(20) in Steroid Side Chains: Scope and Topological Diversification.

PubMed

Li, Houhua; Mazet, Clément

2015-08-26

The stereoselective construction of C20 in steroidal derivatives by a highly diastereoselective Ir-catalyzed isomerization of primary allylic alcohols is reported. A key aspect of this strategy is a straightforward access to geometrically pure steroidal enol tosylate and enol triflate intermediates for subsequent high yielding stereoretentive Negishi cross-coupling reactions to allow structural diversity to be introduced. A range of allylic alcohols participates in the diastereoselective isomerization under the optimized reaction conditions. Electron-rich and electron-poor aryl or heteroaryl substituents are particularly well-tolerated, and the stereospecific nature of the reaction provides indifferently access to the natural C20-(R) and unnatural C20-(S) configurations. Alkyl containing substrates are more challenging as they affect regioselectivity of iridium-hydride insertion. A rationale for the high diastereoselectivities observed is proposed for aryl containing precursors. The scope of our method is further highlighted through topological diversification in the side chain and within the polycyclic domain of advanced and complex steroidal architectures. These findings have the potential to greatly simplify access to epimeric structural analogues of important steroid scaffolds for applications in biological, pharmaceutical, and medical sciences.

Electrophilic fluorination of pyroglutamic acid derivatives: application of substrate-dependent reactivity and diastereoselectivity to the synthesis of optically active 4-fluoroglutamic acids.

PubMed

Konas, D W; Coward, J K

2001-12-28

Electrophilic fluorination of enantiomerically pure 2-pyrrolidinones (4) derived from (L)-glutamic acid has been investigated as a method for the synthesis of single stereoisomers of 4-fluorinated glutamic acids. Reaction of the lactam enolate derived from 9 with NFSi results in a completely diastereoselective monofluorination reaction to yield the monocyclic trans-substituted alpha-fluoro lactam product 21. Unfortunately, a decreased kinetic acidity in 21 and other structurally related monofluorinated products renders them resistant to a second fluorination. In contrast, the bicyclic lactam 12 is readily difluorinated under the standard conditions described to yield the alpha,alpha-difluoro lactam 24. The difference in reactivity between the two types of related lactams is attributed mainly to the presence or lack of a steric interaction between the base used for deprotonation and the protecting group present in the pyrrolidinone substrates. This conclusion was reached based on analysis of the X-ray crystal structure of 21, molecular modeling, and experimental evidence. The key intermediates 21 and 24 are converted to (2S,4R)-4-fluoroglutamic acid and (2S)-4,4-difluoroglutamic acid, respectively.

Platinum nanoparticles: the crucial role of crystal face and colloid stabilizer in the diastereoselective hydrogenation of cinchonidine.

PubMed

Schmidt, Erik; Kleist, Wolfgang; Krumeich, Frank; Mallat, Tamas; Baiker, Alfons

2010-02-15

The preparation of stable metal nanoparticles requires a strong interaction between the (organic) stabilizer and the metal surface that might alter the catalytic properties. This behavior has been described as "poisoning" since the stabilizer normally decreases the catalytic activity due to site blocking. Here we show a striking influence of the stabilizer on the selectivity in the hydrogenation of cinchonidine (CD) over poly(acrylic acid) (PAA)-stabilized Pt nanoparticles with well-defined shape distributions. In the hydrogenation of the heteroaromatic ring of cinchonidine in toluene, the diastereomeric excess of the (S)-hexahydrocinchonidine increased upon increasing Pt{111}/Pt{100} ratio, but this distinct shape selectivity was observed only after the oxidative removal of PAA at 473 K. The use of the as-prepared nanoparticles inverted the major diastereomer to R, and this isomer was formed also in acetic acid. This striking change in the diastereoselectivity indicates that poly(acrylic acid), which remains on the Pt surface after preparation, interacts with CD during hydrogenation almost as strongly as the solvent acetic acid. The PAA stabilizer plays a dual role: it allows one to control the size and shape of the nanoparticles during their synthesis, and it affects the rate and diastereoselectivity of the hydrogenation of CD probably through a "surface-localized acidification".

Studies toward the unique pederin family member psymberin: full structure elucidation, two alternative total syntheses, and analogs.

PubMed

Feng, Yu; Jiang, Xin; De Brabander, Jef K

2012-10-17

Two synthetic approaches to psymberin have been accomplished. A highly convergent first generation synthesis led to the complete stereochemical assignment and demonstrated that psymberin and irciniastatin A are identical compounds. This synthesis featured a diastereoselective aldol coupling between the aryl fragment and a central tetrahydropyran core and a novel one-pot procedure to convert an amide, via intermediacy of a sensitive methyl imidate, to the N-acyl aminal reminiscent of psymberin. The highlights of the second generation synthesis include an efficient iridium-catalyzed enantioselective bisallylation of neopentyl glycol and a stepwise Sonogashira coupling/cycloisomerization/reduction sequence to construct the dihydroisocoumarin unit. The two synthetic avenues were achieved in 17-18 steps (longest linear sequence, ~14-15 isolations) from 3 fragments prepared in 7-8 (first generation) and 3-8 (second generation) steps each. This convergent approach allowed for the preparation of sufficient amounts of psymberin (~ 0.5 g) for follow-up biological studies. Meanwhile, our highly flexible strategy enabled the design and synthesis of multiple analogs, including a psymberin-pederin hybrid, termed psympederin, that proved crucial to a comprehensive understanding of the chemical biology of psymberin and related compounds that will be described in a subsequent manuscript.

Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

PubMed Central

Bai, Da-Chang; Yu, Fei-Le; Wang, Wan-Ying; Chen, Di; Li, Hao; Liu, Qing-Rong; Ding, Chang-Hua; Chen, Bo; Hou, Xue-Long

2016-01-01

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of β-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. Mechanistic studies by both experiments and density functional theory (DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism—nucleophilic attack of enolate oxygen on Palladium followed by C–C bond-forming [3,3']-reductive elimination. PMID:27283477

Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Da -Chang; Yu, Fei -Le; Wang, Wan -Ying

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of beta-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a ( syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. As a result, mechanisticmore » studies by both experiments and density functional theory ( DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination.« less

Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism

DOE PAGES

Bai, Da -Chang; Yu, Fei -Le; Wang, Wan -Ying; ...

2016-06-10

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of beta-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a ( syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. As a result, mechanisticmore » studies by both experiments and density functional theory ( DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism-nucleophilic attack of enolate oxygen on Palladium followed by C-C bond-forming [3,3']-reductive elimination.« less

Reaction of Donor-Acceptor Cyclobutanes with Indoles: A General Protocol for the Formal Total Synthesis of (±)-Strychnine and the Total Synthesis of (±)-Akuammicine.

PubMed

Feng, Liang-Wen; Ren, Hai; Xiong, Hu; Wang, Pan; Wang, Lijia; Tang, Yong

2017-03-06

A ligand-promoted catalytic [4+2] annulation reaction using indole derivatives and donor-acceptor (D-A) cyclobutanes is reported, thus providing an efficient and atom-economical access to versatile cyclohexa-fused indolines with excellent levels of diastereoselectivity and a broad substrate scope. In the presence of a chiral SaBOX ligand, excellent enantioselectivity was realized with up to 94 % ee. This novel synthetic method is applied as a general protocol for the total synthesis of (±)-akuammicine and the formal total synthesis of (±)-strychnine from the same common-core scaffold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric synthesis of 5-arylcyclohexenones by rhodium(I)-catalyzed conjugate arylation of racemic 5-(trimethylsilyl)cyclohexenone with arylboronic acids.

PubMed

Chen, Qian; Kuriyama, Masami; Soeta, Takahiro; Hao, Xinyu; Yamada, Ken-ichi; Tomioka, Kiyoshi

2005-09-29

[reaction: see text] A catalytic asymmetric conjugate arylation of racemic 5-(trimethylsilyl)cyclohex-2-enone with arylboronic acids was catalyzed by 3 mol % chiral amidophosphane- or BINAP-Rh(I) in dioxane-water (10:1) to afford trans- and cis-3-aryl-5-(trimethylsilyl)cyclohexanones in high enantioselectivity. Dehydrosilylation of the product mixture with cupric chloride in DMF gave 5-arylcyclohex-2-enones with up to 93% ee in good yield. Enantiofacial selectivity with chiral phosphane-Rh(I) exceeds the trans-diastereoselectivity that is maintained in the achiral or racemic phosphane-Rh(I)-catalyzed conjugate arylation of 5-(trimethylsilyl)cyclohexenone.

α-Haloaldehydes: versatile building blocks for natural product synthesis.

PubMed

Britton, Robert; Kang, Baldip

2013-02-01

The diastereoselective addition of organometallic reagents to α-chloroaldehydes was first reported in 1959 and occupies a historically significant role as the prototypical reaction for Cornforth's model of stereoinduction. Despite clear synthetic potential for these reagents, difficulties associated with producing enantiomerically enriched α-haloaldehydes limited their use in natural product synthesis through the latter half of the 20th century. In recent years, however, a variety of robust, organocatalytic processes have been reported that now provide direct access to optically enriched α-haloaldehydes and have motivated renewed interest in their use as building blocks for natural product synthesis. This Highlight summarizes the methods available for the enantioselective preparation of α-haloaldehydes and their stereoselective conversion into natural products.

Diastereo- and regioselective addition of thioamide dianions to imines and aziridines: synthesis of N-thioacyl-1,2-diamines and N-thioacyl-1,3-diamines.

PubMed

Shibahara, Fumitoshi; Kobayashi, Shun-ichiro; Maruyama, Toshifumi; Murai, Toshiaki

2013-01-02

Addition reactions of thioamide dianions that were derived from N-arylmethyl thioamides to imines and aziridines were carried out. The reactions of imines gave the addition products of N-thioacyl-1,2-diamines in a highly diastereoselective manner in good-to-excellent yields. The diastereomeric purity of these N-thioacyl-1,2-diamines could be enriched by simple recrystallization. The reduction of N-thioacyl-1,2-diamines with LiAlH(4) gave their corresponding 1,2-diamines in moderate-to-good yields with retention of their stereochemistry. The oxidative-desulfurization/cyclization of an N-thioacyl-1,2-diamine in CuCl(2)/O(2) and I(2)/pyridine systems gave the cyclized product in moderate yield and the trans isomer was obtained as the sole product. On the other hand, a similar cyclization reaction with antiformin (aq. NaClO) as an oxidant gave the cis isomer as the major product. The reactions of N-tosylaziridines gave the addition products of N-thioacyl-1,3-diamines with low diastereoselectivity but high regioselectivity and in good-to-excellent yields. The use of AlMe(3) as an additive improved the efficiency and regioselectivity of the reaction. The stereochemistry of the obtained products was determined by X-ray diffraction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using NMR Spectroscopy to Probe the Chemo- and Diastereoselectivity in the NaBH[subscript 4] Reduction of Benzoin Acetate and Benzoin Benzoate

ERIC Educational Resources Information Center

Saba, Shahrokh; Cagino, Kristen; Bennett, Caitlin

2015-01-01

A pedagogically useful discovery-based undergraduate organic chemistry lab experiment probing the chemo- and diastereoselectivity in the NaBH[subscript 4] reduction of two chiral ketoesters (benzoin acetate and benzoin benzoate) has been developed. This experiment complements a previously described and highly popular discovery-based experiment…

Synthesis of new Cα-tetrasubstituted α-amino acids

PubMed Central

Grauer, Andreas A

2009-01-01

Summary Cα-Tetrasubstituted α-amino acids are important building blocks for the synthesis of peptidemimetics with stabilized secondary structure, because of their ability to rigidify the peptide backbone. Recently our group reported a new class of cyclic Cα-tetrasubstituted tetrahydrofuran α-amino acids prepared from methionine and aromatic aldehydes. We now report the extension of this methodology to aliphatic aldehydes. Although such aldehydes are prone to give aldol products under the reaction conditions used, we were able to obtain the target cyclic amino acids in low to moderate yields and in some cases with good diastereoselectivity. PMID:19259341

Asymmetric 1,2-perfluoroalkyl migration: easy access to enantioenriched α-hydroxy-α-perfluoroalkyl esters.

PubMed

Wang, Pan; Feng, Liang-Wen; Wang, Lijia; Li, Jun-Fang; Liao, Saihu; Tang, Yong

2015-04-15

This study has led to the development of a novel, highly efficient, 1,2-perfluoro-alkyl/-aryl migration process in reactions of hydrate of 1-perfluoro-alkyl/-aryl-1,2-diketones with alcohols, which are promoted by a Zn(II)/bisoxazoline and form α-perfluoro-alkyl/-aryl-substituted α-hydroxy esters. With (-)-8-phenylmenthol as the alcohol, the corresponding menthol esters are generated in high yields with excellent levels of diastereoselectivity. The mechanistic studies show that the benzilic ester-type rearrangement reaction takes place via an unusual 1,2-migration of electron-deficient trifluoromethyl group rather than the phenyl group. The overall process serves as a novel, efficient, and simple approach for the synthesis of highly enantioenriched, biologically relevant α-hydroxy-α-perfluoroalkyl carboxylic acid derivatives.

Enantioselective inhibition of microbial lipolytic enzymes by nonracemic monocyclic enolphosphonate analogues of cyclophostin.

PubMed

Point, Vanessa; Malla, Raj K; Carrière, Frederic; Canaan, Stéphane; Spilling, Christopher D; Cavalier, Jean-François

2013-06-13

Four nonracemic enolphosphonate analogues of Cyclophostin were obtained by asymmetric synthesis, and their absolute configurations at both phosphorus and C-5 carbon chiral centers were unambiguously assigned. The influence of chirality was studied by testing the inhibitory effects of these four stereoisomers toward the lipolytic activity of three microbial lipases: Fusarium solani cutinase, Rv0183, and LipY from Mycobacterium tuberculosis . Cutinase was highly diastereoselective for the (Sp) configuration using (Sc) inhibitors, whereas no obvious stereopreference at phosphorus was observed with (Rc) compounds. Conversely, Rv0183 exhibited strong enantioselective discrimination for (Sp) configuration regardless of the chirality at the asymmetric carbon atom. Lastly, LipY discriminated only the unusual diastereoisomeric configuration (Rc, Rp) leading to the most potent inhibitor. This work, which provides a fundamental premise for the understanding of the stereoselective relationships between nonracemic enolphosphonates and their inhibitory activity, also opens new prospects on the design and synthesis of highly specific enantioselective antimicrobial agents.

Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives.

PubMed

Kalek, Marcin; Fu, Gregory C

2015-07-29

Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity.

A Rhodium(I)-Xylyl-BINAP Catalyzed Asymmetric Ynamide-[2 + 2 + 2] Cycloaddition in the Synthesis of Optically Enriched N,O-Biaryls

PubMed Central

Oppenheimer, Jossian; Johnson, Whitney L.; Figueroa, Ruth; Hayashi, Ryuji; Hsung, Richard P.

2009-01-01

A rhodium(I)-xylyl-BINAP catalyzed asymmetric [2 + 2 + 2] cycloaddition of achiral conjugated aryl ynamides with various diynes is described here. This asymmetric cycloaddition provides a series of structurally interesting chiral N,O-biaryls with excellent enantioselectivity along with a modest diastereoselectivity with respect to both C-C and C-N axial chirality. PMID:20161177

A Pauson-Khand and ring-expansion approach to the aquariane ring system.

PubMed

Thornton, Paul D; Burnell, D Jean

2006-07-20

[Structure: see text] The carbocyclic ring system of the aquariolide diterpenes has been synthesized by two routes involving a diastereoselective Pauson-Khand reaction and subsequent ring expansion. In one route, a tetracyclic enone was elaborated to generate the nine-membered ring by Grob fragmentation. In the second approach, a spirocyclic tricycle underwent a facile anionic oxy-Cope rearrangement to complete the synthesis of the desired ring system.

Stereocontrolled synthesis of polyhydroxylated bicyclic azetidines as a new class of iminosugars.

PubMed

Malinowski, Maciej; Hensienne, Raphaël; Kern, Nicolas; Tardieu, Damien; Bodlenner, Anne; Hazelard, Damien; Compain, Philippe

2018-06-12

We report herein the development of a stereodivergent route towards polyhydroxylated bicyclic azetidine scaffolds, namely 6-azabicyclo[3.2.0]heptane derivatives. The strategy hinges on a common bicyclic β-lactam precursor, which is forged by way of a rare example of a cationic Dieckmann-type reaction, followed by IBX-mediated desaturation. Substrate-controlled diastereoselective oxidations then allow the divergent preparation of novel iminosugar mimics.

Pyrrolidine and Piperidine Formation Via Copper(II) Carboxylate Promoted Intramolecular Carboamination of Unactivated Olefins: Diastereoselectivity and Mechanism

PubMed Central

Sherman, Eric S.; Fuller, Peter H.; Kasi, Dhanalakshmi; Chemler, Sherry R.

2008-01-01

An expanded substrate scope and in depth analysis of the reaction mechanism of the copper(II) carboxylate promoted intramolecular carboamination of unactivated alkenes is described. This method provides access to N-functionalized pyrrolidines and piperidines. Both aromatic and aliphatic γ- and δ-alkenyl N-arylsulfonamides undergo the oxidative cyclization reaction efficiently. N-Benzoyl-2-allylaniline also underwent the oxidative cyclization. The terminal olefin substrates examined were more reactive than those with internal olefins, and the latter terminated in elimination rather than carbon-carbon bond formation. The efficiency of the reaction was enhanced by the use of more organic soluble copper(II) carboxylate salts, copper(II) neodecanoate in particular. The reaction times were reduced by the use of microwave heating. High levels of diastereoselectivity were observed in the synthesis of 2,5-disubstituted pyrrolidines, wherein the cis substitution pattern predominates. The mechanism of the reaction is discussed in the context of the observed reactivity and in comparison to analogous reactions promoted by other reagents and conditions. Our evidence supports a mechanism wherein the N-C bond is formed via intramolecular syn aminocupration and the C-C bond is formed via intramolecular addition of a primary carbon radical to an aromatic ring. PMID:17428100

Asymmetric nucleophilic monofluorobenzylation of carbonyl compounds: synthesis of enantiopure vic-fluorohydrins and α-fluorobenzylketones.

PubMed

Arroyo, Yolanda; Sanz-Tejedor, M Ascensión; Parra, Alejandro; García Ruano, José Luis

2012-04-23

Asymmetric nucleophilic monofluoroalkylation of a broad range of aldehydes with an α-fluoro-γ-sulfinylbenzyl carbanion takes place with complete control of the facial selectivity at the carbanion and good to high anti-diastereoselectivity to give easily separable mixtures of two optically pure 1,2-fluorohydrin derivatives (up to 24:1 anti/syn). Separation and removal of the p-tolylsulfinyl group with tBuLi provides enantiomerically pure anti-1,2-disubstituted-1,2-fluorohydrins, whereas α-fluorobenzylketones can be obtained by desulfinylation of the mixture followed by pyridinium chlorochromate oxidation (one-pot process). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C 2-symmetric building block: a strategy for the synthesis of decanolide natural products.

PubMed

Schmidt, Bernd; Kunz, Oliver

2013-01-01

Starting from the conveniently available ex-chiral pool building block (R,R)-hexa-1,5-diene-3,4-diol, the ten-membered ring lactones stagonolide E and curvulide A were synthesized using a bidirectional olefin-metathesis functionalization of the terminal double bonds. Key steps are (i) a site-selective cross metathesis, (ii) a highly diastereoselective extended tethered RCM to furnish a (Z,E)-configured dienyl carboxylic acid and (iii) a Ru-lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation.

Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions. Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.

Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligand–binding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolutionmore » X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the enzyme active site. These ligand–binding site interactions are possibly responsible for their potent activity.« less

Asymmetric synthesis of α-alkenyl homoallylic primary amines via 1,2-addition of Grignard reagent to α,β-unsaturated phosphonyl imines.

PubMed

Xiong, Yiwen; Mei, Haibo; Xie, Chen; Han, Jianlin; Li, Guigen; Pan, Yi

2013-01-01

A series of chiral N -phosphonyl protected α-alkenyl homoallylic primary amines were synthesized by asymmetric addition of allylmagnesium bromide Grignard reagent towards chiral α,β-unsaturated imines. Only 1,2-adduct was obtained for all the imines with good yields and excellent diastereoselectivities. The chiral auxiliary could be easily removed under simple conditions, giving free multiple functionalized primary amines.

Chemo- and Diastereoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions Using N-Boc-α-amino Aldehydes.

PubMed

Haghshenas, Pouyan; Gravel, Michel

2016-09-16

N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.

Tandem Reactions for Streamlining Synthesis

PubMed Central

HUSSAIN, MAHMUD M.; WALSH, PATRICK J.

2009-01-01

CONSPECTUS In 1980 Sharpless and Katsuki introduced the asymmetric epoxidation of prochiral allylic alcohols (the Sharpless-Katsuki Asymmetric Epoxidation), which enabled the rapid synthesis of highly enantioenriched epoxy alcohols. This reaction was a milestone in the development of asymmetric catalysis because it was the first highly enantioselective oxidation reaction. Furthermore, it provided access to enantioenriched allylic alcohols that are now standard starting materials in natural product synthesis. In 1981 Sharpless and coworkers made another seminal contribution by describing the kinetic resolution (KR) of racemic allylic alcohols. This work demonstrated that small-molecule catalysts could compete with enzymatic catalysts in KRs. For these pioneering works, Sharpless was awarded the 2001 Nobel Prize with Knowles and Noyori. Despite these achievements, the Sharpless KR is not an efficient method to prepare epoxy alcohols with high enantiomeric excess (ee). First, the racemic allylic alcohol must be prepared and purified. KR of the racemic allylic alcohol must be stopped at low conversion, because the ee of the product epoxy alcohol decreases as the KR progresses. Thus, better methods to prepare epoxy alcohols containing stereogenic carbinol carbons are needed. This Account summarizes our efforts to develop one-pot methods for the synthesis of various epoxy alcohols and allylic epoxy alcohols with high enantio-, diastereo-, and chemoselectivity. Our laboratory developed titanium-based catalysts for use in the synthesis of epoxy alcohols with tertiary carbinols. The catalysts are involved in the first step, which is an asymmetric alkyl or allyl addition to enones. The resulting intermediates are then subjected to a titanium-directed diastereoselective epoxidation to provide tertiary epoxy alcohols. Similarly, the synthesis of acyclic epoxy alcohols begins with asymmetric additions to enals and subsequent epoxidation. The methods described here enable the synthesis of skeletally diverse epoxy alcohols. PMID:18710197

Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.

PubMed

Lemonnier, Gérald; Lion, Cédric; Quirion, Jean-Charles; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe

2012-08-01

Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemoenzymatic synthesis of C-4'-spiro-oxetanoribonucleosides.

PubMed

Sharma, Vivek K; Kumar, Manish; Sharma, Deepti; Olsen, Carl E; Prasad, Ashok K

2014-09-19

Novozyme-435-mediated diastereoselective deacylation of one of the two diastereotopic acyloxymethyl groups in 5-O-acyl-4-C-acyloxymethyl-3-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranose has been achieved in quantitative yield. The exclusive selectivity of the lipase for the 5-O-acyl over the 4-C-acyloxymethyl group in the substrate was confirmed by chemical transformation of enzymatically monodeacetylated compound to 1,2-O-isopropylidene-C-4-spiro-oxetanoribofuranose. Further, the selective biocatalytic deacylation methodology has been utilized for the efficient synthesis of C-4'-spiro-oxetanoribonucleosides of uracil (U) and thymine (T) in 37 and 45% overall yields, respectively.

Enantiomerically Pure Acetals in Organic Synthesis: Resolutions and Diastereoselective Alkylations of Alpha-Hydroxy Esters

DTIC Science & Technology

1990-01-01

sensitivity of the alkylating agent to the reaction conditions. In either case , a decision was made to use 5-iodo-2- methyl -l-pentene as the alkylating ...agent, and the reaction conditions. In most cases the diastereomeric products of the alkylation were also separated by column chromatography. This...equatorially substituted product. Oxidation of the alcohol to the ketone followed by treatment with an alkyl Grignard reagent gave only the product which

Synthesis of functionalized imidazolidine-2-thiones via NHC/base-promoted aza-benzoin/aza-acetalization domino reactions.

PubMed

Di Carmine, Graziano; Ragno, Daniele; De Risi, Carmela; Bortolini, Olga; Giovannini, Pier Paolo; Fantin, Giancarlo; Massi, Alessandro

2017-10-25

A strategy for the synthesis of biologically relevant 5-hydroxy-imidazolidine-2-thione derivatives is presented. A novel class of α-sulfonylamines have been suitably prepared (46-81% yield) as precursors of formal benzylidenethiourea acceptors; these are generated in situ and intercepted by N-heterocyclic carbene (NHC)-activated aldehydes affording open-chain aza-benzoin-type adducts, which in turn undergo an intramolecular aza-acetalization reaction in a one-pot fashion. A thiazolium salt/triethylamine couple proved to be the more effective system to trigger the domino sequence giving the target heterocycles in good yields (45-97%) and diastereoselectivities (up to 99 : 1 dr). The multigram scale synthesis and elaboration of a selected 5-hydroxy-imidazolidine-2-thione compound is also described.

Diastereoselective sp2-sp3 coupling of sugar enol ethers with unactivated cycloalkenes: new entries to C-branched sugars.

PubMed

Hussain, Nazar; Tatina, Madhu Babu; Rasool, Faheem; Mukherjee, Debaraj

2016-10-25

Sugar enol ethers undergo efficient coupling at C-2 with unactivated cycloalkenes under a low Pd loading affording allylic substitution products. High diastereoselectivity was observed at the allylic centre with sterically hindered substrates. Generation of a π-allyl complex by the Pd(ii) catalyst via cleavage of the allylic C-H bond of the cycloalkene may be responsible for the formation of sp 2 -sp 3 coupling products.

Inversion of Configuration at the Phosphorus Nucleophile in the Diastereoselective and Enantioselective Synthesis of P-Stereogenic syn-Phosphiranes from Chiral Epoxides.

PubMed

Muldoon, Jake A; Varga, Balázs R; Deegan, Meaghan M; Chapp, Timothy W; Eördögh, Ádám M; Hughes, Russell P; Glueck, David S; Moore, Curtis E; Rheingold, Arnold L

2018-04-23

Nucleophilic substitution results in inversion of configuration at the electrophilic carbon center (S N 2) or racemization (S N 1). The stereochemistry of the nucleophile is rarely considered, but phosphines, which have a high barrier to pyramidal inversion, attack electrophiles with retention of configuration at P. Surprisingly, cyclization of bifunctional secondary phosphine alkyl tosylates proceeded under mild conditions with inversion of configuration at the nucleophile to yield P-stereogenic syn-phosphiranes. DFT studies suggested that the novel stereochemistry results from acid-promoted tosylate dissociation to yield an intermediate phosphenium-bridged cation, which undergoes syn-selective cyclization. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations.

PubMed

Sorochinsky, Alexander E; Aceña, José Luis; Moriwaki, Hiroki; Sato, Tatsunori; Soloshonok, Vadim A

2013-10-01

Alkylations of chiral or achiral Ni(II) complexes of glycine Schiff bases constitute a landmark in the development of practical methodology for asymmetric synthesis of α-amino acids. Straightforward, easy preparation as well as high reactivity of these Ni(II) complexes render them ready available and inexpensive glycine equivalents for preparing a wide variety of α-amino acids, in particular on a relatively large scale. In the case of Ni(II) complexes containing benzylproline moiety as a chiral auxiliary, their alkylation proceeds with high thermodynamically controlled diastereoselectivity. Similar type of Ni(II) complexes derived from alanine can also be used for alkylation providing convenient access to quaternary, α,α-disubstituted α-amino acids. Achiral type of Ni(II) complexes can be prepared from picolinic acid or via recently developed modular approach using simple secondary or primary amines. These Ni(II) complexes can be easily mono/bis-alkylated under homogeneous or phase-transfer catalysis conditions. Origin of diastereo-/enantioselectivity in the alkylations reactions, aspects of practicality, generality and limitations of this methodology is critically discussed.

Reactivity, chemoselectivity, and diastereoselectivity of the oxyfunctionalization of chiral allylic alcohols and derivatives in microemulsions: comparison of the chemical oxidation by the hydrogen peroxide/sodium molybdate system with the photooxygenation.

PubMed

Nardello, Véronique; Caron, Laurent; Aubry, Jean-Marie; Bouttemy, Sabine; Wirth, Thomas; Saha-Möller Chantu, R; Adam, Waldemar

2004-09-01

The chiral allylic alcohols 1a-d and their acetate (1e) and silyl ether (1f) derivatives have been oxidized by the H2O2/MoO4(2)- system, a convenient and efficient chemical source of singlet oxygen. This chemical peroxidation (formation of the allylic hydroperoxides 2) has been conducted in various media, which include aqueous solutions, organic solvents, and microemulsions. The reactivity, chemoselectivity, and diastereoselectivity of this chemical oxidation are compared to those of the sensitized photooxygenation, with the emphasis on preparative applications in microemulsion media. While a similar threo diastereoselectivity is observed for both modes of peroxidation, the chemoselectivity differs significantly, since in the chemical oxidation with the H2O2/MoO4(2)- system the undesirable epoxidation by the intermediary peroxomolybdate competes efficiently with the desirable peroxidation by the in situ generated singlet oxygen. A proper choice of the type of microemulsion and the reaction conditions furnishes a high chemoselectivity (up to 97%) in favor of threo-diastereoselective (up to 92%) peroxidation. Copyright 2004 American Chemical Society

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

Tetrahydrofuran Calpha-tetrasubstituted amino acids: two consecutive beta-turns in a crystalline linear tripeptide.

PubMed

Maity, Prantik; Zabel, Manfred; König, Burkhard

2007-10-12

The synthesis of tetrahydrofuran Calpha-tetrasubstituted amino acids (TAAs) and their effect on the conformation in small peptides are reported. The synthesis starts from the protein amino acid methionine, which is protected at the C and N terminus and converted into the corresponding sulfonium salt by alkylation. Simple base treatment in the presence of an aryl aldehyde leads to the formation of tetrahydrofuran tetrasubstituted Calpha-amino acids in a highly diastereoselective (trans/cis ratio up to 97:3) reaction with moderate to good yields (35-78%) depending on the aldehyde used. Palladium-catalyzed coupling reactions allow a subsequent further functionalization of the TAA. The R,S,S-TAA-Ala dipeptide amide adopts a beta-turn type I conformation, whereas its S,R,S isomer does not. The R,S,S-Gly-TAA-Ala tripeptide amide shows in the solid state and in solution a conformation of two consecutive beta-turn type III structures, stabilized by i+3-->i intramolecular hydrogen bonds.

Concise Total Synthesis of (-)-Affinisine Oxindole, (+)-Isoalstonisine, (+)-Alstofoline, (-)-Macrogentine, (+)-Na -Demethylalstonisine, (-)-Alstonoxine A, and (+)-Alstonisine.

PubMed

Stephen, Michael Rajesh; Rahman, M Toufiqur; Tiruveedhula, V V N Phani Babu; Fonseca, German O; Deschamps, Jeffrey R; Cook, James M

2017-11-07

A highly enantio- and diastereoselective strategy to access any member of the sarpagine/macroline family of oxindole alkaloids via internal asymmetric induction was developed from readily available d-(+)-tryptophan. At the center of this approach was the diastereospecific generation of the spiro[pyrrolidine-3,3'-oxindole] moiety at an early stage via a tert-butyl hypochlorite-promoted oxidative rearrangement of a chiral tetrahydro-β-carboline derivative. This key branching point determined the spatial configuration at the C-7 spiro center to be entirely 7R or 7S. Other key stereospecific processes were the asymmetric Pictet-Spengler reaction and Dieckmann cyclization, which were scalable to the 600 and 150 gram levels, respectively. Execution of this approach resulted in first enantiospecific total synthesis of (+)-isoalstonisine and (-)-macrogentine from the chitosenine series (7R), as well as (+)-alstonisine, (+)-alstofoline, (-)-alstonoxine A and (+)-N a -demethylalstonisine from the alstonisine series (7S). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diastereoselective Synthesis of Symmetrical and Unsymmetrical Tetrahydropyridines Catalyzed by Bi(III) Immobilized on Triazine Dendrimer Stabilized Magnetic Nanoparticles.

PubMed

Asadi, Beheshteh; Landarani-Isfahani, Amir; Mohammadpoor-Baltork, Iraj; Tangestaninejad, Shahram; Moghadam, Majid; Mirkhani, Valiollah; Amiri Rudbari, Hadi

2017-06-12

Unsymmetrical 1,2,5,6-tetrahydropyridine-3-carboxylates were obtained for the first time from a five-component Fe 3 O 4 @TDSN-Bi(III)-catalyzed reaction of aryl aldehydes, aryl amines, and ethyl acetoacetate. This magnetically separable catalyst enabled the selective incorporation of two different aryl amines or two different aryl aldehydes into the product, and provided excellent yields, short reaction times, mild reaction conditions, satisfactory catalyst recyclability, and low catalyst loading.

Evolution of a short route to strychnine by using the samarium-diiodide-induced cascade cyclization as a key step.

PubMed

Beemelmanns, Christine; Reissig, Hans-Ulrich

2015-06-01

This comprehensive report accounts the development of a highly diastereoselective samarium diiodide-induced cascade reaction of substituted indolyl ketones. The complexity-generating transformation with SmI2 allows the diastereoselective generation of three stereogenic centers including one quaternary center in one step. The obtained tetra- or pentacyclic dihydroindole derivatives are structural motifs of many monoterpene indole alkaloids, and their subsequent transformations gave way to one of the shortest approaches towards strychnine (14 % overall yield in ten steps, or 10 % overall yield in eight steps). During the course of this report we discuss the influence of substituents on the cyclization step, plausible mechanistic scenarios for the SmI2 -induced cascade reaction, diastereoselective reductive amination, and regioselective dehydratization protocols towards the pentacyclic core structure of strychnos alkaloids. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantiomerically Enriched α-Methyl Amino Acids. Use of an Acyclic, Chiral Alanine-Derived Dianion with a High Diastereofacial Bias.†

PubMed Central

Berkowitz, David B.; Smith, Marianne K.

2018-01-01

Hindered esters derived from N-benzoylalanine and the following chiral alcohols have been synthesized: (1) (−)-isopinocampheol; (2) (−)-trans-2-phenylcyclohexanol and (3) (−)-8-phenylmenthol. Sequential treatment of these esters with LDA (1.2 equiv.) and n-butyllithium (2.4 equiv.) at −78°C in THF generates the corresponding chiral dianions. Alkylation of each of these with benzyl bromide reveals that only the (−)-8-phenylmenthyl auxiliary confers a high diastereofacial bias upon its derivative dianion. In fact, that dianion (6) consistently displays diastereomeric ratios in the range of 89:11 to 94:6 for alkylations with a spectrum of nine alkyl halides. If one recrystallization step is included, a single diastereomeric product may be obtained, as is demonstrated for the benzylation of 6. Of particular note, the alkylation with 3,4-bis(tert-butyldimethylsilyloxy)benzyl bromide (18) (94:6 diast. ratio, 72% yield) constitutes a formal synthesis of the clinically important antihypertensive (S)-α-methyl-DOPA (Aldomet), in enantiomerically enriched from. In all cases studied, yields are markedly improved, yet diastereoselectivities unchanged, by the addition of 10% HMPA to the reaction milieu. The (−)-8-phenylmenthol chiral auxiliary is conveniently recovered via ester cleavage with KO2/18-crown-6, following alkylation. Complete deprotection affords enantiomerically enriched (S)-α-methyl amino acids, in all cases examined, indicating that dianion 6 displays a substantial bias in favor of si face alkylation. This sense of diastereoselection is consistent with a chain-extended, internal chelate model for the reactive conformation of the dianion.

Biocatalytic route to C-3'-azido/-hydroxy-C-4'-spiro-oxetanoribonucleosides.

PubMed

Kumar, Manish; Sharma, Vivek K; Kumar, Rajesh; Prasad, Ashok K

2015-11-19

The lipase, Novozyme(®)-435, exclusively deacetylates the 5-O-acetyl over 4-C-acetyloxymethyl group of almost identical reactivity in 5-O-acetyl-4-C-acetyloxymethyl-3-azido-3-deoxy-1,2-O-isopropylidene-α-D-ribofuranose that led to the development of first and efficient synthesis of 3'-azido-/3'-amino-C-4'-spiro-oxetanoribonucleosides T, U, C and A in 20-24% overall yields. The X-ray study on the compound obtained by tosylation of lipase-mediated monodeacetylated product unambiguously confirmed the point of diastereoselective monodeacetylation on diacetoxy-azido-ribofuranose derivative. The capability of Novozyme(®)-435 for selective deacylation of 5-O-acetyl group in 5-O-acetyl-4-C-acetyloxymethyl-3-O-benzyl-1,2-O-isopropylidene-α-D-ribofuranose recently discovered by us has been successfully used for the synthesis of C-4'-spiro-oxetanoribonucleosides A and C in good yields. These results clearly indicate that the broader substrate specificity and highly selective capability of Novozyme(®)-435 for carrying out acetylation/deacetylation reactions can be utilized for the development of environment friendly selective methodologies in organic synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Formation of multi-stereogenic centers using a catalytic diastereoselective Henry reaction.

PubMed

Arai, Takayoshi; Taneda, Yoshinori; Endo, Yoko

2010-11-14

A diastereoselective Henry reaction of chiral aldehydes with nitroalkanes was developed using a chiral sulfonyldiamine (L1)-CuCl complex. The reaction of (R)-2-phenylpropanal and nitromethane was smoothly catalyzed by the (S,S,S)-L1-CuCl complex to give the adduct with 99/1 syn/anti selectivity in 99% ee. In the reaction of (S)-2-phenylpropanal and nitroethane, the (R,R,R)-L1-CuCl catalyst yielded the expected three contiguous stereogenic centers in a highly syn-selective Henry reaction.

Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

PubMed Central

Brenna, Davide; Massolo, Elisabetta; Puglisi, Alessandra; Rossi, Sergio; Celentano, Giuseppe; Capriati, Vito

2016-01-01

Different deep eutectic solvent (DES) mixtures were studied as reaction media for the continuous synthesis of enantiomerically enriched products by testing different experimental set-ups. L-Proline-catalysed cross-aldol reactions were efficiently performed in continuo, with high yield (99%), anti-stereoselectivity, and enantioselectivity (up to 97% ee). Moreover, using two different DES mixtures, the diastereoselectivity of the process could be tuned, thereby leading to the formation, under different experimental conditions, to both the syn- and the anti-isomer with very high enantioselectivity. The excess of cyclohexanone was recovered and reused, and the reaction could be run and the product isolated without the use of any organic solvent by a proper choice of DES components. The dramatic influence of the reaction media on the reaction rate and stereoselectivity of the process suggests that the intimate architecture of DESs deeply influences the reactivity of different species involved in the catalytic cycle. PMID:28144332

Metal-free, mild, nonepimerizing, chemo- and enantio- or diastereoselective N-alkylation of amines by alcohols via oxidation/imine-iminium formation/reductive amination: a pragmatic synthesis of octahydropyrazinopyridoindoles and higher ring analogues.

PubMed

Khan, Imran A; Saxena, Anil K

2013-12-06

A mild step and atom-economical nonepimerizing chemo- and enantioselective N-alkylating procedure has been developed via oxidation/imine-iminium formation/reduction cascade using TEMPO-BAIB-HEH-Brønsted acid catalysis in DMPU as solvent and a stoichiometric amount of amine. The optimized conditions were further extended for the nonenzymatic kinetic resolution of the chiral amine thus formed under nonenzymatic in situ hydrogen-transfer conditions using VAPOL-derived phosphoric acid (VAPOL-PA) as the Brønsted acid catalyst. The enantioselective cascade of the presented reaction was successfully utilized in the synthesis of octahydropyrazinopyridoindole and its higher ring analogues.

Reagent-based DOS: developing a diastereoselective methodology to access spirocyclic- and fused heterocyclic ring systems.

PubMed

Damerla, V Surendra Babu; Tulluri, Chiranjeevi; Gundla, Rambabu; Naviri, Lava; Adepally, Uma; Iyer, Pravin S; Murthy, Y L N; Prabhakar, Nampally; Sen, Subhabrata

2012-10-01

Herein, we report a diversity-oriented-synthesis (DOS) approach for the synthesis of biologically relevant molecular scaffolds. Our methodology enables the facile synthesis of fused N-heterocycles, spirooxoindolones, tetrahydroquinolines, and fused N-heterocycles. The two-step sequence starts with a chiral-bicyclic-lactam-directed enolate-addition/substitution step. This step is followed by a ring-closure onto the built-in scaffold electrophile, thereby leading to stereoselective carbocycle- and spirocycle-formation. We used in silico tools to calibrate our compounds with respect to chemical diversity and selected drug-like properties. We evaluated the biological significance of our scaffolds by screening them in two cancer cell-lines. In summary, our DOS methodology affords new, diverse scaffolds, thereby resulting in compounds that may have significance in medicinal chemistry. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lewis base activation of Lewis acids: catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes.

PubMed

Denmark, Scott E; Chung, Won-Jin

2008-06-20

A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diastereoselectivity could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the alpha-oxygen provide enantiomerically enriched alpha,beta-dihydroxy esters with high syn-diastereoselectivity, whereas the tert-butyldimethylsilyl ketene acetals derived from bulky esters of alpha-methoxyacetic acid provide enantiomerically enriched alpha,beta-dihydroxy esters with high anti-diastereoselecitvity.

Diversity-oriented asymmetric catalysis (DOAC): stereochemically divergent synthesis of thiochromanes using an imidazoline-aminophenol-nickel-catalyzed Michael/Henry reaction.

PubMed

Arai, Takayoshi; Yamamoto, Yushi

2014-03-21

The (S,S)-diphenylethylenediamine-derived imidazoline-aminophenol-Ni complex catalyzed tandem asymmetric Michael/Henry reaction of 2-mercaptobenzaldehydes with β-nitrostyrenes to give the corresponding (2S,3R,4R)-2-aryl-3-nitrothiochroman-4-ols in up to 99% diastereoselectivity with 95% ee was demonstrated in diversity-oriented asymmetric catalysis. Reduction of the nitro group of the chiral thiochromanes gave a new series of (2S,3R,4R)-3-amino-2-arylthiochroman-4-ols with retention of the strereoselectivity.

Direct Access to 2,3,4,6-Tetrasubstituted Tetrahydro-2H-pyrans via Tandem SN2'-Prins Cyclization.

PubMed

Scoccia, Jimena; Pérez, Sixto J; Sinka, Victoria; Cruz, Daniel A; López-Soria, Juan M; Fernández, Israel; Martín, Víctor S; Miranda, Pedro O; Padrón, Juan I

2017-09-15

A new, direct, and diastereoselective synthesis of activated 2,3,4,6-tetrasubstituted tetrahydro-2H-pyrans is described. In this reaction, iron(III) catalyzed an S N 2'-Prins cyclization tandem process leading to the creation of three new stereocenters in one single step. These activated tetrahydro-2H-pyran units are easily derivatizable through CuAAC conjugations in order to generate multifunctionalized complex molecules. DFT calculations support the in situ S N 2' reaction as a preliminary step in the Prins cyclization.

Substrate-Controlled Diastereoselectivity Reversal in NHC-Catalyzed Cross-Benzoin Reactions Using N-Boc-N-Bn-Protected α-Amino Aldehydes.

PubMed

Haghshenas, Pouyan; Quail, J Wilson; Gravel, Michel

2016-12-16

The effectiveness of utilizing N-Bn-N-Boc-α-amino aldehydes in cross-benzoin reactions with heteroaromatic aldehydes is demonstrated. The reaction is both chemoselective and syn-selective, making it complementary to the anti-selective cross-benzoin reaction of NHBoc-α-amino aldehydes. Good diastereoselectivity is obtained for a variety of amino aldehydes, including nonhindered ones. A Felkin-Anh model can be used to rationalize the observed diastereoselectivity.

N-Methylpyrrolidone Hydroperoxide/Cs2 CO3 as an Excellent Reagent System for the Hydroxy-Directed Diastereoselective Epoxidation of Electron-Deficient Olefins.

PubMed

Victor, Napoleon John; Gana, Janardhanan; Muraleedharan, Kannoth Manheri

2015-10-12

This report introduces N-methylpyrrolidone hydroperoxide (NMPOOH)/base as an excellent reagent system for hydroxy-directed syn selective epoxidation of electron-deficient olefins, characterized by high diastereoselectivity, short reaction times and remarkable chemoselectivity, especially in presence of oxidatively labile nitrogen or sulfur atoms. NMPOOH also proves efficient in the oxidation of electron-deficient aromatic aldehydes, in the removal of oxazolidinone chiral auxiliary, and in the functionalization of alkenes and alkynes, showing wide application potential. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Flow Asymmetric Propargylation: Development of Continuous Processes for the Preparation of a Chiral β-Amino Alcohol.

PubMed

Li, Hui; Sheeran, Jillian W; Clausen, Andrew M; Fang, Yuan-Qing; Bio, Matthew M; Bader, Scott

2017-08-01

The development of a flow chemistry process for asymmetric propargylation using allene gas as a reagent is reported. The connected continuous process of allene dissolution, lithiation, Li-Zn transmetallation, and asymmetric propargylation provides homopropargyl β-amino alcohol 1 with high regio- and diastereoselectivity in high yield. This flow process enables practical use of an unstable allenyllithium intermediate. The process uses the commercially available and recyclable (1S,2R)-N-pyrrolidinyl norephedrine as a ligand to promote the highly diastereoselective (32:1) propargylation. Judicious selection of mixers based on the chemistry requirement and real-time monitoring of the process using process analytical technology (PAT) enabled stable and scalable flow chemistry runs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of ω-Oxo Amino Acids and trans-5-Substituted Proline Derivatives Using Cross-Metathesis of Unsaturated Amino Acids.

PubMed

Salih, Nabaz; Adams, Harry; Jackson, Richard F W

2016-09-16

A range of 7-oxo, 8-oxo, and 9-oxo amino acids, analogues of 8-oxo-2-aminodecanoic acid, one of the key components of the cyclic tetrapeptide apicidin, have been prepared by a three-step process involving copper-catalyzed allylation of serine-, aspartic acid-, and glutamic acid-derived organozinc reagents, followed by cross-metathesis of the resulting terminal alkenes with unsaturated ketones and hydrogenation. The intermediate 7-oxo-5-enones underwent a highly diastereoselective (dr ≥96:4) acid-catalyzed aza-Michael reaction to give trans-2,5-disubstituted pyrrolidines, 5-substituted proline derivatives. The aza-Michael reaction was first observed when the starting enones were allowed to stand in solution in deuterochloroform but can be efficiently promoted by catalytic amounts of dry HCl.

Carbanion-Accelerated Claisen Rearrangements Asymmetric Induction with Chiral Phosphorus-Stabilized Anions‡

PubMed Central

Denmark, Scott E.; Marlin, John E.; Rajendra, G.

2012-01-01

The carbanion-accelerated Claisen rearrangement has been extended to include phosphorus carbanion-stabilizing groups. The appropriately substituted allyl vinyl ethers are synthesized by the nucleophilic addition of allyloxides to phosphorus-substituted allenes, which are obtained in one step from simple starting materials. The phosphorus-stabilized, carbanion-accelerated Claisen rearrangements proceed rapidly at room temperature in high yield, and the rearrangements are highly site and stereoselective. The first examples of asymmetric induction in the Claisen rearrangement with chiral, phosphorus, anion-stabilizing groups are described. The observed asymmetric induction is highly dependent on the structure of the auxiliary and the metal counterion involved. Both internal and relative diastereoselectivity are high. A model for the observed sense of internal diastereoselectivity is proposed that is founded in the current understanding of the structure of phosphorus-stabilized anions. PMID:23101563

Diastereoselective synthesis and molecular docking studies of novel fused tetrahydropyridine derivatives as new inhibitors of HIV protease

NASA Astrophysics Data System (ADS)

Mohammadi, Ali A.; Taheri, Salman; Amouzegar, Ali; Ahdenov, Reza; Halvagar, Mohammad Reza; Sadr, Ahmad Shahir

2017-07-01

An efficient one-pot, catalyst-free, and four-components procedure for the synthesis of novel 10b-hydroxy-4-nitro-5-phenyl-2,3,5,5a-tetrahydro-1H-imidazo[1,2-a]indeno[2,1-e]pyridin-6(10bH)-one derivatives from corresponding diamine, nitro ketene dithioacetal, aldehydes and 1,3-indandione in ethanol has been achieved upon a Knoevenagel condensation-Michael addition-tautomerism-cyclisation sequence. All the newly synthesized compounds were screened for molecular docking studies. Molecular docking studies were carried out using the crystal structure of HIV protease enzyme. Some of the compounds obtain minimum binding energy and good affinity toward the active pocket of HIV protease enzyme in compare with Saquinavir as a standard HIV protease inhibitor.

Synthesis of the Paralytic Shellfish Poisons (+)-Gonyautoxin 2, (+)-Gonyautoxin 3, and (+)-11,11-Dihydroxysaxitoxin.

PubMed

Mulcahy, John V; Walker, James R; Merit, Jeffrey E; Whitehead, Alan; Du Bois, J

2016-05-11

The paralytic shellfish poisons are a collection of guanidine-containing natural products that are biosynthesized by prokaryote and eukaryote marine organisms. These compounds bind and inhibit isoforms of the mammalian voltage-gated Na(+) ion channel at concentrations ranging from 10(-11) to 10(-5) M. Here, we describe the de novo synthesis of three paralytic shellfish poisons, gonyautoxin 2, gonyautoxin 3, and 11,11-dihydroxysaxitoxin. Key steps include a diastereoselective Pictet-Spengler reaction and an intramolecular amination of an N-guanidyl pyrrole by a sulfonyl guanidine. The IC50's of GTX 2, GTX 3, and 11,11-dhSTX have been measured against rat NaV1.4, and are found to be 22 nM, 15 nM, and 2.2 μM, respectively.

Polycyclic ferrocenyl(dihydro)thiazepine derivatives: Diastereo-selective synthesis, characterization, electrochemical behavior, theoretical and biological investigation.

PubMed

Sánchez García, Jessica J; Toledano-Magaña, Yanis; Flores-Alamo, Marcos; Martínez-Klimova, Elena; Galindo-Murillo, Rodrigo; Hernández-Ayala, Luis F; Ortiz-Frade, Luis; García-Ramos, Juan C; Klimova, Elena I

2017-01-01

The reaction of E-2-ferrocenylmethylidenetetralones and E,E-2,6-bis-(ferrocenylmethylidene)-cyclohexanone with 2-aminothiophenol proceed with high diastereoselectivity, forming the ~4.5:1 mixture of trans- and cis-isomers of polycyclic ferrocenylthiazepines, respectively. The reactions of E,E-2,5-bis-(ferrocenylmethylidene)cyclopentanone and E,E-3,5-bis-(ferrocenylmethylidene)-1-methyl-4-piperidone with 2-aminothiophenol take place stereo specifically to form the diastereomeric tricyclic thiazepines of cis- and trans-configuration, respectively. The structures of the obtained compounds were established by IR, 1 H and 13 C NMR spectroscopy and mass-spectrometry. The structures of the trans-tetralino[1,2a]-, trans-5,7-dimethyltetralino[1,2a]-2-ferrocenyl [1,5]benzo-2,3-dihydrothiazepines and cis-5-ferrocenyl-methylidenecyclopentano[1,2a]-2-ferrocenyl- [1,5]benzo-2,3-dihydrothiazepine were confirmed by X-ray diffraction analysis. An electrochemical study reveals that the diferrocenyl derivatives belong to a Class I compounds of the Robin-Day classification. This behavior is explained by the analysis of frontier orbitals as calculated by density functional theory, showing that only one ferrocenyl unit participates in the generation of HOMO and LUMO orbitals. Compounds 4a and 4c showed similar capacity to inhibit the proliferation of HM1: IMSS trophozoite cultures than the first choice drug for human amoebiasis treatment, metronidazole. Morphological changes induced in the trophozoites after drug exposure suggest a redox in balance as the probable mechanism of the parasite death. Copyright © 2016 Elsevier Inc. All rights reserved.

Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activation of the Nrf2 transcription factor and selective cytotoxic activity.

PubMed

Elhalem, Eleonora; Recio, Rocío; Werner, Sabine; Lieder, Franziska; Calderón-Montaño, José Manuel; López-Lázaro, Miguel; Fernández, Inmaculada; Khiar, Noureddine

2014-11-24

Reported is an enantiodivergent approach for the synthesis of both enantiomers of sulforaphane (SFN) homologues with different chain lengths between the sulfinyl sulfur and the isothiocyanate groups and different substituents on the sulfinyl sulfur. The homologues were designed in order to unravel the effect of all the diversity elements included in sulforaphane's structure. The key step of the approach is the diastereoselective synthesis of both sulfinate ester epimers at sulfur, using as single chiral auxiliary the sugar derived diacetone-d-glucose. The approach allows the first synthesis of both enantiomers of 5-methylsulfinylpentyl isothiocyanate, and the biologically important 6-methylsulfinylhexyl isothiocyanate (6-HITC) found in Japanese horseradish, wasabi (Wasabia japonica). The ability of the synthesized compounds as inductors of phase II detoxifying enzymes has been studied by determining their ability to activate the cytoprotective transcription factor Nrf2. The cytotoxic activity of all the synthesized compounds against human lung adenocarcinoma (A549) and foetal lung fibroblasts (MRC-5) is also reported. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Imino Transfer Hydrogenation Reductions.

PubMed

Wills, Martin

2016-04-01

This review contains a summary of recent developments in the transfer hydrogenation of C=N bonds, with a particularly focus on reports from within the last 10 years and asymmetric transformations. However, earlier work in the area is also discussed in order to provide context for the more recent results described. I focus strongly on the Ru/TsDPEN class of asymmetric transfer hydrogenation reactions originally reported by Noyori et al., together with examples of their applications, particularly to medically valuable target molecules. The recent developments in the area of highly active imine-reduction catalysts, notably those based on iridium, are also described in some detail. I discuss diastereoselective reduction methods as a route to the synthesis of chiral amines using transfer hydrogenation. The recent development of a methodology for positioning reduction complexes within chiral proteins, permitting the generation of asymmetric reduction products through a directed modification of the protein environment in a controlled manner, is also discussed.

When is an imine not an imine? Unusual reactivity of a series of Cu(II) imine-pyridine complexes and their exploitation for the Henry reaction.

PubMed

Cooper, Christine J; Jones, Matthew D; Brayshaw, Simon K; Sonnex, Benjamin; Russell, Mark L; Mahon, Mary F; Allan, David R

2011-04-14

In this paper we report the synthesis and solid-state structures for a series of pyridine based Cu(II) complexes and preliminary data for the asymmetric Henry reaction. Interestingly, the solid-state structures indicate the incorporation of an alcohol into one of the imine groups of the ligand, forming a rare α-amino ether group. The complexes have been studied via single crystal X-ray diffraction, EPR spectroscopy and mass spectrometry. Intriguingly, it has been observed that the alcohol only adds to one of the imine moieties. Density functional theory (DFT) calculations have also been employed to rationalise the observed structures. The Cu(II) complexes have been tested in the asymmetric Henry reaction (benzaldehyde + nitromethane or nitroethane) with ee's up to 84% being achieved as well as high conversions and modest diastereoselectivities. © The Royal Society of Chemistry 2011

Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization.

PubMed

Johnston, Craig P; Kothari, Abhishek; Sergeieva, Tetiana; Okovytyy, Sergiy I; Jackson, Kelvin E; Paton, Robert S; Smith, Martin D

2014-02-01

5-Endo-trig cyclizations are generally considered to be kinetically unfavourable, as described by Baldwin's rules. Consequently, observation of this mode of reaction under kinetic control is rare. This is usually ascribed to challenges in achieving appropriate approach trajectories for orbital overlap in the transition state. Here, we describe a highly enantio- and diastereoselective route to complex indanes bearing all-carbon quaternary stereogenic centres via a 5-endo-trig cyclization catalysed by a chiral ammonium salt. Through computation, the preference for the formally disfavoured 5-endo-trig Michael reaction over the formally favoured 5-exo-trig Dieckmann reaction is shown to result from thermodynamic contributions to the innate selectivity of the nucleophilic group, which outweigh the importance of the approach trajectory as embodied by Baldwin's rules. Our experimental and theoretical findings demonstrate that geometric and stereoelectronic constraints may not be decisive in the observed outcome of irreversible ring-closing reactions.

Chemoenzymatic synthesis of differentially protected 3-deoxysugars

NASA Astrophysics Data System (ADS)

Gillingham, Dennis G.; Stallforth, Pierre; Adibekian, Alexander; Seeberger, Peter H.; Hilvert, Donald

2010-02-01

3-Deoxysugars are important constituents of complex carbohydrates. For example, 2-keto-3-deoxy-D-manno-octulosonic acid (KDO) is an essential component of lipopolysaccharides in Gram-negative bacteria, 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN) is widely found in carbohydrates of the bacterial cell wall and in lower vertebrates, and sialic acid is a common cap of mammalian glycoproteins. Although ready access to such sugars would benefit the creation of vaccine candidates, antibiotics and small-molecule drugs, their chemical synthesis is difficult. Here we present a simple chemoenzymatic method for preparing differentially protected 3-deoxysugar derivatives from readily available starting materials. It exploits the promiscuous aldolase activity of the enzyme macrophomate synthase (MPS) to add pyruvate enolate diastereoselectively to a wide range of structurally complex aldehydes. A short synthesis of KDN illustrates the utility of this approach. Enzyme promiscuity, which putatively fosters large functional leaps in natural evolution, has great promise as a source of synthetically useful catalytic transformations.

Liquid-assisted grinding and ion pairing regulates percentage conversion and diastereoselectivity of the Wittig reaction under mechanochemical conditions.

PubMed

Denlinger, Kendra Leahy; Ortiz-Trankina, Lianna; Carr, Preston; Benson, Kingsley; Waddell, Daniel C; Mack, James

2018-01-01

Mechanochemistry is maturing as a discipline and continuing to grow, so it is important to continue understanding the rules governing the system. In a mechanochemical reaction, the reactants are added into a vessel along with one or more grinding balls and the vessel is shaken at high speeds to facilitate a chemical reaction. The dielectric constant of the solvent used in liquid-assisted grinding (LAG) and properly chosen counter-ion pairing increases the percentage conversion of stilbenes in a mechanochemical Wittig reaction. Utilizing stepwise addition/evaporation of ethanol in liquid-assisted grinding also allows for the tuning of the diastereoselectivity in the Wittig reaction.

Heterocyclic alpha-alkylidene cyclopentenones obtained via a Pauson-Khand reaction of amino acid derived allenynes. A scope and limitation study directed toward the preparation of a tricyclic pyrrole library.

PubMed

Brummond, Kay M; Curran, Dennis P; Mitasev, Branko; Fischer, Stefan

2005-03-04

The synthesis of a novel class of tricyclic pyrroles has been accomplished by using a Pauson-Khand/Stetter/Paal-Knorr reaction sequence. Full details of the Pauson-Khand reaction of amino acid tethered allenynes 4a-e and 9a-d are disclosed. The study of this reaction led to the discovery of an unprecedented substituent effect on the diastereoselectivity of the Mo(CO)6 mediated allenic Pauson-Khand reaction. It was found that amino acid tethered allenynes with aromatic side chains afford alpha-alkylidene cyclopentenones with the opposite diastereoselectivity compared to those with aliphatic side chains. This effect has been attributed to complexation of the metal mediator to the aromatic ring in the substrate. Furthermore, an isomerization of one of the diastereomers of the alpha-alkylidene cyclopentenones was encountered, leading to eventual decomposition. The stable diastereomers were found to react well in the Stetter reaction leading to 1,4-diketones that were converted to pyrroles. The observation that the first generation of 2-alkyl-substituted pyrroles was unstable led to a second generation of 2-carboxamide pyrroles with sufficient stability for biological tests which are in progress.

Diastereoselective addition of 2H-2-oxo-1,4,2-oxazaphosphinanes to aldehydes and imines.

PubMed

Pirat, Jean-Luc; Monbrun, Jérôme; Virieux, David; Volle, Jean-Noël; Tillard, Monique; Cristau, Henri-Jean

2005-09-02

[reaction: see text] Diastereoselective additions of 2-hydrogeno-2-oxo-1,4,2-oxazaphosphinanes to aldehydes and imines are described. alpha,alpha'-Diaminophosphinic and alpha-amino-alpha'-hydroxyphosphinic derivatives were obtained with de's ranging from 24 to 90%.

Ene reaction of singlet oxygen, triazolinedione, and nitrosoarene with chiral deuterium-labeled allylic alcohols: the interdependence of diastereoselectivity and regioselectivity discloses mechanistic insights into the hydroxy-group directivity.

PubMed

Adam, Waldemar; Bottke, Nils; Krebs, Oliver; Lykakis, Ioannis; Orfanopoulos, Michael; Stratakis, Manolis

2002-12-04

The ene reaction of singlet oxygen ((1)O(2)), triazolinedione (TAD), and nitrosoarene, specifically 4-nitronitrosobenzene (ArNO), with the tetrasubstituted 1,3-allylically strained, chiral allylic alcohol 3,4-dimethylpent-3-en-2-ol (2) leads to the threo-configured ene products in high diastereoselectivity, a consequence of the hydroxy-group directivity. Hydrogen bonding favors formation of the threo-configured encounter complex threo-EC in the early stage of ene reaction. For the analogous twix deuterium-labeled allylic alcohol Z-2-d(3), a hitherto unrecognized dichotomy between (1)O(2) and the ArNO and TAD enophiles is disclosed in the regioselectivity of the tetrasubstituted alcohol: Whereas for ArNO and TAD, hydrogen bonding with the allylic hydroxy group dictates the regioselectivity (twix selectivity), for (1)O(2), the cis effect dominates (twin/trix selectivity). From the interdependence between the twix/twin regioselectivity and the threo/erythro diastereoselectivity, it has been recognized that the enophile also attacks the allylic alcohol from the erythro pi face without assistance by hydrogen bonding with the allylic hydroxy functionality.

5-(Methylthio)tetrazoles as Versatile Synthons in the Stereoselective Synthesis of Polycyclic Pyrazolines via Photoinduced Intramolecular Nitrile Imine–Alkene 1,3-Dipolar Cycloaddition

PubMed Central

Pla, Daniel; Tan, Derek S.; Gin, David Y.

2014-01-01

A key thioether substituent in readily accessible 2-alkyl-5-(methylthio)tetrazoles enables facile photoinduced denitrogenation and intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of polycyclic pyrazoline products with excellent diastereoselectivity. The methylthio group red-shifts the UV absorbance of the tetrazole, obviating the requirement in all previous substrate systems for at least one aryl substituent, and can subsequently be converted into a variety of other functionalities. This synthetic platform has been applied to the concise total syntheses of the alkaloid natural products (±)-newbouldine and withasomnine. PMID:25114776

Asymmetric Synthesis of Hydrocarbazoles Catalyzed by an Octahedral Chiral-at-Rhodium Lewis Acid.

PubMed

Huang, Yong; Song, Liangliang; Gong, Lei; Meggers, Eric

2015-12-01

A bis-cyclometalated chiral-at-metal rhodium complex catalyzes the Diels-Alder reaction between N-Boc-protected 3-vinylindoles (Boc = tert-butyloxycarbonyl) and β-carboxylic ester-substituted α,β-unsaturated 2-acyl imidazoles with good-to-excellent regioselectivity (up to 99:1) and excellent diastereoselectivity (>50:1 d.r.) as well as enantioselectivity (92-99% ee) under optimized conditions. The rhodium catalyst serves as a chiral Lewis acid to activate the 2-acyl imidazole dienophile by two-point binding and overrules the preferred regioselectivity of the uncatalyzed reaction. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of cis-C-Iodo-N-Tosyl-Aziridines using Diiodomethyllithium: Reaction Optimization, Product Scope and Stability, and a Protocol for Selection of Stationary Phase for Chromatography

PubMed Central

2013-01-01

The preparation of C-iodo-N-Ts-aziridines with excellent cis-diastereoselectivity has been achieved in high yields by the addition of diiodomethyllithium to N-tosylimines and N-tosylimine–HSO2Tol adducts. This addition-cyclization protocol successfully provided a wide range of cis-iodoaziridines, including the first examples of alkyl-substituted iodoaziridines, with the reaction tolerating both aryl imines and alkyl imines. An ortho-chlorophenyl imine afforded a β-amino gem-diiodide under the optimized reaction conditions due to a postulated coordinated intermediate preventing cyclization. An effective protocol to assess the stability of the sensitive iodoaziridine functional group to chromatography was also developed. As a result of the judicious choice of stationary phase, the iodoaziridines could be purified by column chromatography; the use of deactivated basic alumina (activity IV) afforded high yield and purity. Rearrangements of electron-rich aryl-iodoaziridines have been promoted, selectively affording either novel α-iodo-N-Ts-imines or α-iodo-aldehydes in high yield. PMID:23738857

Rapid synthesis of carbohydrate derivatives, including mimetics of C-linked disaccharides and C-linked aza disaccharides, using the hetero-Diels-Alder reaction.

PubMed

Burland, Peter A; Coisson, David; Osborn, Helen M I

2010-11-05

In this work we demonstrate the value of performing a hetero-Diels-Alder reaction (HDAR) between Danishefsky's diene and a range of aldehydes or imines, under microwave irradiation. By using a range of aldehydes and imines, including those derived from carbohydrates, access to functionalized 2,3-dihydro-4H-pyran-4-ones or 2,3-dihydro-4-pyridinones in good to excellent synthetic yields is possible. A particular strength of the methodology is its ability to access mimetics of C-linked disaccharides and C-linked aza disaccharides, targets of current therapeutic interest, in a rapid, convenient, and diastereoselective manner. The effect of high pressure on the HDARs involving carbohydrate-derived aldehydes and imines is also explored, with enhancement in yields occurring for the aldehyde substrates. Finally, HDARs using carbohydrate derived ketones, enones, and enals are described under a range of conditions. Optimum results were obtained under high-pressure conditions, with highly functionalized carbohydrate derivatives being afforded, in good yields, in this way.

Selective Synthesis of 5- or 6-Aryl Octahydrocyclopenta[b]pyrroles from a Common Precursor Through Control of Competing Pathways in a Pd-Catalyzed Reaction

PubMed Central

Ney, Joshua E.; Wolfe, John P.

2009-01-01

The Pd/phosphine-catalyzed reaction of 1 with aryl bromides leads to the selective synthesis of either 6-aryl octahydrocyclopenta[b]pyrroles (3), the corresponding 5-aryl isomers 5, diarylamine 2, or hexahydrocyclopenta[b]pyrrole 4 depending on the structure of the phosphine ligand. These transformations are effective with a variety of different aryl bromides, and provide 3-5 with excellent levels of diastereoselectivity (dr ≥ 20:1). The changes in product distribution are believed to derive from the influence of Pd-catalyst structure on the relative rates of reductive elimination, β-hydride elimination, alkene insertion, and alkene dissociation processes in a mechanistically complex reaction. The effect of phosphine ligand structure on product distribution is described in detail, along with analysis of a proposed mechanism for these transformations. PMID:15954769

Expeditious diastereoselective synthesis of elaborated ketones via remote Csp3-H functionalization

NASA Astrophysics Data System (ADS)

Shu, Wei; Lorente, Adriana; Gómez-Bengoa, Enrique; Nevado, Cristina

2017-01-01

The quest for selective C-H functionalization reactions, able to provide new strategic opportunities for the rapid assembly of molecular complexity, represents a major focus of the chemical community. Examples of non-directed, remote Csp3-H activation to forge complex carbon frameworks remain scarce due to the kinetic stability and thus intrinsic challenge associated to the chemo-, regio- and stereoselective functionalization of aliphatic C-H bonds. Here we describe a radical-mediated, directing-group-free regioselective 1,5-hydrogen transfer of unactivated Csp3-H bonds followed by a second Csp2-H functionalization to produce, with exquisite stereoselectivity, a variety of elaborated fused ketones. This study demonstrates that aliphatic acids can be strategically harnessed as 1,2-diradical synthons and that secondary aliphatic C-H bonds can be engaged in stereoselective C-C bond-forming reactions, highlighting the potential of this protocol for target-oriented natural product and pharmaceutical synthesis.

Stereodivergent Mannich reaction of bis(trimethylsilyl)ketene acetals with N-tert-butanesulfinyl imines by Lewis acid or Lewis base activation, a one-pot protocol to obtain chiral β-amino acids.

PubMed

Cantú-Reyes, Margarita; Alvarado-Beltrán, Isabel; Ballinas-Indilí, Ricardo; Álvarez-Toledano, Cecilio; Hernández-Rodríguez, Marcos

2017-09-20

We report a one-pot synthesis of chiral β 2,2,3 -amino acids by the Mannich addition of bistrimethylsilyl ketene acetals to N-tert-butanesulfinyl imines followed by the removal of the chiral auxiliary. The synthesis and isolation of pure β-amino acid hydrochlorides were conducted under mild conditions, without strong bases and this method is operationally simple. The stereoselective reaction was promoted by two different activation methods that lead to different stereoisomers: (1) Lewis Acid (LA) catalysis with boron trifluoride diethyl etherate and (2) Lewis Base (LB) catalysis with tetrabutylammonium difluorotriphenylsilicate. The reaction presented good diastereoselectivity with LB activation and moderate to good dr with LA catalysis. The exceptions in both protocols were imines with electron donating groups in the aromatic ring.

A Facile One-Pot Construction of Succinimide-Fused Spiro[Pyrrolidine-2,3'-Oxindoles] via 1,3-Dipolar Cycloaddition Involving 3-Amino Oxindoles and Maleimides.

PubMed

Jin, Lunqiang; Liang, Feng

2018-03-05

Increasing interests have been invested in the development of synthetic strategies toward the construction of spiro[pyrrolidine-2,3'-oxindole], which is the core structural skeleton in some compounds with diverse biological activities. In this work, an efficient diastereoselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated in situ from 3-amino oxindoles and aldehydes with maleimides has been described. The protocol provides a facile and efficient access to structurally diverse succinimide-fused spiro[pyrrolidine-2,3'-oxindole] compounds in good to high yields (up to 93%) with moderate to excellent diastereoselectivities (up to >95:5). The relative stereochemistry of cycloaddition products has been assigned by X-ray diffraction analysis.

Diastereoselective DNA Cleavage Recognition by Ni(II)•Gly-Gly-His Derived Metallopeptides

PubMed Central

Fang, Ya-Yin; Claussen, Craig A.; Lipkowitz, Kenny B.; Long, Eric C.

2008-01-01

Site-selective DNA cleavage by diastereoisomers of Ni(II)•Gly-Gly-His-derived metallopeptides was investigated through high-resolution gel analyses and molecular dynamics simulations. Ni(II)•L-Arg-Gly-His and Ni(II)•D-Arg-Gly-His (and their respective Lys analogues) targeted A/T-rich regions; however, the L-isomers consistently modified a sub-set of available nucleotides within a given minor groove site while the D-isomers differed in both their sites of preference and ability to target individual nucleotides within some sites. In comparison, Ni(II)•L-Pro-Gly-His and Ni(II)•D-Pro-Gly-His were unable to exhibit a similar diastereoselectivity. Simulations of the above systems, along with Ni(II)•Gly-Gly-His, indicated that the stereochemistry of the amino-terminal amino acid produces either an isohelical metallopeptide that associates stably at individual DNA sites (L-Arg or L-Lys) or, with D-Arg and D-Lys, a non-complementary metallopeptide structure that cannot fully employ its side chain nor amino-terminal amine as a positional stabilizing moiety. In contrast, amino-terminal Pro-containing metallopeptides of either stereochemistry, lacking an extended side chain directed toward the minor groove, did not exhibit a similar diastereoselectivity. While the identity and stereochemistry of amino acids located in the amino-terminal peptide position influenced DNA cleavage, metallopeptide diastereoisomers containing L- and D-Arg (or Lys) within the second peptide position did not exhibit diastereoselective DNA cleavage patterns; simulations indicated that a positively-charged amino acid in this location alters the interaction of the metallopeptide equatorial plane and the minor groove leading to an interaction similar to Ni(II)•Gly-Gly-His. PMID:16522100

N-Boc amines to oxazolidinones via Pd(II)/bis-sulfoxide/Brønsted acid co-catalyzed allylic C-H oxidation.

PubMed

Osberger, Thomas J; White, M Christina

2014-08-06

A Pd(II)/bis-sulfoxide/Brønsted acid catalyzed allylic C-H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C-H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C-H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration.

N-Boc Amines to Oxazolidinones via Pd(II)/Bis-sulfoxide/Brønsted Acid Co-Catalyzed Allylic C–H Oxidation

PubMed Central

2015-01-01

A Pd(II)/bis-sulfoxide/Brønsted acid catalyzed allylic C–H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C–H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C–H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration. PMID:24999765

HIGHLY DIASTEREOSELECTIVE MICHAEL REACTION UNDER SOLVENT-FREE CONDITIONS USING MICROWAVES: CONJUGATE ADDITION OF FLAVANONE TO ITS CHALCONE PRECURSOR

EPA Science Inventory

Microwave-assisted reaction of 2'-hydroxychalcones in the presence of DBU resulted in the formation of hitherto unknown dimers by conjugate addition of the intermediate cyclic ketone to the starting enone.

HIGHLY DISATEREOSELECTIVE MICHAEL ADDITION OF FLAVANONE TO ITS CHALCONE PRECURSOR UNDER SOLVENT-FREE CONDITIONS USING MICROWAVES [POSTER

EPA Science Inventory

Substituted 2'-hydroxychalcones were found to give an equilibrium mixture of the starting chalcone and the corresponding flavanone inf 4.6-1:3 ratio in the presence of DBU gave two hitherto unknown diasteromeric dimers in a highly diastereoselective Michael addition of the carban...

[Stereoselective synthesis of polyhydroxylated amines using (S)-pyroglutamic acid derivatives].

PubMed

Ikota, Nobuo

2014-01-01

Naturally occurring polyhydroxylated amines such as (+)-1-deoxynojirimycin, polyoxamic acid, anisomycin, (-)swainsonine, and alexine stereoisomers, which have interesting biological activities including glucosidase- and mannosidase-inhibitory activity, immunoregulatory activity, and antibacterial effects, were synthesized stereoselectively starting from (S)-pyroglutamic acid derivatives. α,β-Unsaturated lactams ((S)-5-hydroxymethyl-2-oxo-3-pyrroline derivatives), α,β-unsaturated δ-lactone ((S)-4-amino-2-penten-5-olide derivative), and E-olefin ((S,E)-methyl-4-amino-5-hydroxypent-2-enoate derivative) from (S)-pyroglutamic acid derivatives were dihydroxylated using OsO4 in the presence of N-methyl morpholine N-oxide (NMO) to afford various chiral building blocks with different configurations. The stereoselectivity of cis-dihydroxylation for α,β-unsaturated lactams and α,β-unsaturated δ-lactone was very high, while the stereoselectivity was low for E-olefin. Therefore, the double asymmetric induction of E-olefin using K2OsO4 with chiral ligands was successively applied to yield high stereoselectivity. (2R,3S)-2-Hydroxymethyl-3-hydroxypyrrolidine and Gaissman-Weiss lactone, important intermediates for the preparation of pyrrolizidine alkaloids, were synthesized from a (3R,4R,5R)-3,4-dihydroxy-5-hydroxymethyl-2-pyrrolidinone derivative derived from α,β-unsatulated lactam. (+)-1-Deoxynojirimycin was synthesized from a (2S,3R,4R)-methyl 4-amino-2,3,5-trihydroxypentanoate derivative of E-olefin. (-)-Swainsonine and its stereoisomers were synthesized from (2R,3S,4R)- or (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine derivatives of α,β-unsaturated δ-lactone or α,β-unsaturated lactam. The key reaction was diastereoselective allylation of the aldehyde derived from the corresponding 2-hydroxymethylpyrrolidine derivatives with various allylation reagents. The high diastereoselectivity could be explained by cyclic chelate formation between metals and the α-aminocarbonyl group or β-alkoxycarbonyl group, in which the nucleophile approaches from the less hindered face. Four alexine stereoisomers were synthesized from (2R,3R,4S,5R)- and (2R,3R,4S,5S)-2,3-dihydroxymethyl-3,4-dihydroxyl pyrrolidine derivatives of α,β-unsaturated lactam.

Inverse temperature dependence in the diastereoselective addition of Grignard reagents to a tetrahydrofurfural.

PubMed

Mowat, Jeffrey; Kang, Baldip; Fonovic, Branden; Dudding, Travis; Britton, Robert

2009-05-21

A remarkable example of inverse-temperature-dependent diastereoselectivity was uncovered while investigating the addition of Grignard reagents to a 3-hydroxytetrahydrofurfural. The free hydroxyl group in the tetrahydrofurfural was found to play a key role in these processes, a result corroborated through a series of DFT calculations that also highlighted an entropic preference for the formation of one diastereomer.

Stereodivergent catalytic doubly diastereoselective nitroaldol reactions using heterobimetallic complexes.

PubMed

Sohtome, Yoshihiro; Kato, Yuko; Handa, Shinya; Aoyama, Naohiro; Nagawa, Keita; Matsunaga, Shigeki; Shibasaki, Masakatsu

2008-06-05

Stereodivergent construction of three contiguous stereocenters in catalytic doubly diastereoselective nitroaldol reactions of alpha-chiral aldehydes with nitroacetaldehyde dimethyl acetal using two types of heterobimetallic catalysts is described. A La-Li-BINOL (LLB) catalyst afforded anti,syn-nitroaldol products in >20:1-14:1 selectivity, and a Pd/La/Schiff base catalyst afforded complimentary syn,syn-nitroaldol products in 10:1-5:1 selectivity.

Diastereoselective formation of metallamacrocyclic (arene)Ru(II) and CpRh(III) complexes.

PubMed

Lehaire, Marie-Line; Scopelliti, Rosario; Herdeis, Lorenz; Polborn, Kurt; Mayer, Peter; Severin, Kay

2004-03-08

The reaction of [(arene)RuCl(2)](2) (arene = cymene, 1,3,5-C(6)H(3)Me(3)) and [CpRhCl(2)](2) half-sandwich complexes with tridentate heterocyclic ligands in the presence of base has been investigated. In all cases, the chloro-ligands were substituted to give metallacyclic products with ring sizes between 4 and 18 atoms. The cyclization occurs in a highly diastereoselective fashion with chiral recognition between the different metal fragments. The complexes were comprehensively characterized by elemental analysis, NMR spectroscopy, and single crystal X-ray crystallography. For 2-hydroxy-nicotinic acid and 2-amino-nicotinic acid, dinuclear structures were obtained (15-17) whereas for 2,3-dihydroxyquinoline, 2,3-dihydroxyquinoxaline, and 6-methyl-2,3-phenazinediol, trimeric assemblies were found (19-22), and for 4-imidazolecarboxylic acid, a tetrameric assembly (18) was found.

Amphidinolide B: Total Synthesis, Structural Investigation and Biological Evaluation

PubMed Central

Lu, Liang; Zhang, Wei; Nam, Sangkil; Horne, David A.; Jove, Richard

2013-01-01

The total synthesis of amphidinolide B1 and the proposed structure of amphidinolide B2 has been accomplished. Key aspects of this work include the development of a practical, non-transition metal mediated method for the construction of the C13-C15 diene, the identification of α-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B2 and diastereomers thereof display potent anti-tumor activities with IC50 values ranging from 3.3 nM to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B2 is over 12-fold more potent than the C8,9-epimer and C18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity. PMID:23406192

Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S,S)-(+)-pseudoephedrine as chiral auxiliary; enantioselective synthesis of 3-substituted pyrrolidines.

PubMed

Alonso, Beatriz; Ocejo, Marta; Carrillo, Luisa; Vicario, Jose L; Reyes, Efraim; Uria, Uxue

2013-01-18

We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.

Chiral metallohelices enantioselectively target hybrid human telomeric G-quadruplex DNA

PubMed Central

Zhao, Andong; Howson, Suzanne E.; Ren, Jinsong; Scott, Peter; Wang, Chunyu

2017-01-01

Abstract The design and synthesis of metal complexes that can specifically target DNA secondary structure has attracted considerable attention. Chiral metallosupramolecular complexes (e.g. helicates) in particular display unique DNA-binding behavior, however until recently few examples which are both water-compatible and enantiomerically pure have been reported. Herein we report that one metallohelix enantiomer Δ1a, available from a diastereoselective synthesis with no need for resolution, can enantioselectively stabilize human telomeric hybrid G-quadruplex and strongly inhibit telomerase activity with IC50 of 600 nM. In contrast, no such a preference is observed for the mirror image complex Λ1a. More intriguingly, neither of the two enantiomers binds specifically to human telomeric antiparallel G-quadruplex. To the best of our knowledge, this is the first example of one pair of enantiomers with contrasting selectivity for human telomeric hybrid G-quadruplex. Further studies show that Δ1a can discriminate human telomeric G-quadruplex from other telomeric G-quadruplexes. PMID:28398500

Virtually complete control of simple and face diastereoselectivity in the Michael addition reactions between achiral equivalents of a nucleophilic glycine and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones: practical method for preparation of beta-substituted pyroglutamic acids and prolines.

PubMed

Soloshonok, Vadim A; Ueki, Hisanori; Tiwari, Rohit; Cai, Chaozhong; Hruby, Victor J

2004-07-23

This study demonstrates a new strategy for controlling the stereochemical outcome of the Michael addition reactions between nucleophilic glycine equivalents and alpha,beta-unsaturated carboxylic acid derivatives: The addition reactions between achiral Ni(II)-complex of the Schiff base of glycine with o-[N-alpha-pycolylamino]acetophenone and (S)- or (R)-3-(E-enoyl)-4-phenyl-1,3-oxazolidin-2-ones were shown to occur at room temperature in the presence of nonchelating organic bases and, most notably, with very high stereoselectivity at both newly formed stereogenic centers. Thus, the chiral 4-phenyl-1,3-oxazolidin-2-one moiety was found to control efficiently both face diastereoselectivities of the glycine derived enolate and the C,C double bond of the Michael acceptor. The new strategy developed in this work is methodologically superior to previous methods, most notably in terms of generality and synthetic efficiency. Excellent chemical yields and diastereoselectivities, combined with the simplicity of the experimental procedures, render the present method of immediate use for preparing various 3-substituted pyroglutamic acids and related amino acids (glutamic acids, glutamines, prolines, etc.) available via conventional transformations of the former.

Ligand-controlled, norbornene-mediated, regio- and diastereoselective rhodium-catalyzed intramolecular alkene hydrosilylation reactions.

PubMed

Hua, Yuanda; Nguyen, Hiep H; Scaggs, William R; Jeon, Junha

2013-07-05

Ligand-controlled, norbornene-mediated, regio- and diastereoselective rhodium-catalyzed intramolecular alkene hydrosilylation of homoallyl silyl ethers (1) exploiting either BINAP or 1,6-bis(diphenylphosphino)hexane (dpph) has been developed. This method permits selective access to either trans-oxasilacyclopentanes (trans-2) or oxasilacyclohexanes (3) at will. A substoichiometric amount of norbornene markedly increased both yield and selectivity. A norbornene-mediated hydride shuttle process is discussed.

Exploiting [2+2] cycloaddition chemistry: achievements with allenes.

PubMed

Alcaide, Benito; Almendros, Pedro; Aragoncillo, Cristina

2010-02-01

The allene moiety represents an excellent partner for the [2+2] cycloaddition with alkenes and alkynes, affording the cyclobutane and cyclobutene skeletons in a single step. This strategy has been widely studied under thermal, photochemical and microwave induced conditions. More recently, the use of transition metal catalysis has been introduced as an alternative relying on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of polycyclic compounds in a regio- and stereoselective fashion. This critical review focuses on the most recently developed [2+2] cycloadditions on allenes along with remarkable early works accounting for the mechanism, the regio- and diastereoselectivity of the cycloadducts formed (103 references).

Studies of Azetidin-2-one as a Reactive Enolate Synthon of β-Alanine for Condensations with Aldehydes and Ketones.

PubMed

Williams, David R; Donnell, Andrew F; Kammler, David C; Ward, Sarah A; Taylor, Levin

2016-11-04

Studies describe formation of the lithium enolate of N-(4-methoxybenzyloxy)azetidin-2-one (1) and characterization of representative aldol reactions with aldehydes and ketones. Diastereoselectivity features the production of anti-aldol adducts from α,β-unsaturated ketones and α-branched aliphatic aldehydes. The stereoselectivity is rationalized via closed, six-membered transition-state arrangements leading to the formation of Felkin-Anh and anti-Felkin products. Examples illustrate the direct incorporation of monocyclic β-lactams into a variety of molecular architectures. The utility of 1 as an enolate synthon of homoglycine (β-alanine) is illustrated by the efficient synthesis of novel β-amino acid derivatives, including complex 4-hydroxy-2-pyridinones.

A Highly Diastereoselective Oxidant Contributes to Ligninolysis by the White Rot Basidiomycete Ceriporiopsis subvermispora

Treesearch

Daniel J. Yelle; Alexander N. Kapich; Carl J. Houtman; Fachuang Lu; Vitaliy I. Timokhin; Raymond C. Fort Jr.; John Ralph; Kenneth E. Hammel

2014-01-01

The white rot basidiomycete Ceriporiopsis subvermispora delignifies wood selectively and has potential biotechnological applications. Its ability to remove lignin before the substrate porosity has increased enough to admit enzymes suggests that small diffusible oxidants contribute to delignification. A key question is whether these unidentified...

Development of an enantioselective synthetic route to neocarzinostatin chromophore and its use for multiple radioisotopic incorporation.

PubMed

Myers, Andrew G; Glatthar, Ralf; Hammond, Marlys; Harrington, Philip M; Kuo, Elaine Y; Liang, Jun; Schaus, Scott E; Wu, Yusheng; Xiang, Jia-Ning

2002-05-15

A convergent, enantioselective synthetic route to the natural product neocarzinostatin chromophore (1) is described. Synthesis of the chromophore aglycon (2) was targeted initially. Chemistry previously developed for the synthesis of a neocarzinostatin core model (4) failed in the requisite 1,3-transposition of an allylic silyl ether when applied toward the preparation of 2 with use of the more highly oxygenated substrates 27 and 54. An alternative synthetic plan was therefore developed, based upon a proposed reduction of the epoxy alcohol 58 to form the aglycon 2, a transformation that was achieved in a novel manner, using a combination of the reagents triphenylphosphine, iodine, and imidazole. The successful route to 1 and 2 began with the convergent coupling of the epoxydiyne 15, obtained in 9 steps (43% overall yield) from D-glyceraldehyde acetonide, and the cyclopentenone (+)-14, prepared in one step (75-85% yield) from the prostaglandin intermediate (+)-16, affording the alcohol 22 in 80% yield and with > or =20:1 diastereoselectivity. The alcohol 22 was then converted into the epoxy alcohol 58 in 17 steps with an average yield of 92% and an overall yield of 22%. Key features of this sequence include the diastereoselective Sharpless asymmetric epoxidation of allylic alcohol 81 (98% yield); intramolecular acetylide addition within the epoxy aldehyde 82, using Masamune's lithium diphenyltetramethyldisilazide base (85% yield); selective esterification of the diol 84 with the naphthoic acid 13 followed by selective cleavage of the chloroacetate protective group in situ to furnish the naphthoic acid ester 85 in 80% yield; and elimination of the tertiary hydroxyl group within intermediate 88 using the Martin sulfurane reagent (79% yield). Reductive transposition of the product epoxy alcohol (58) then formed neocarzinostatin chromophore aglycon (2, 71% yield). Studies directed toward the glycosylation of 2 focused initially on the preparation of the N-methylamino --> hydroxyl replacement analogue 3, an alpha-D-fucose derivative of neocarzinostatin chromophore, formed in 42% yield by a two-step Schmidt glycosylation-deprotection sequence. For the synthesis of 1, an extensive search for a suitable 2'-N-methylfucosamine glycosyl donor led to the discovery that the reaction of 2 with the trichloroacetimidate 108, containing a free N-methylamino group, formed the alpha-glycoside 114 selectively in the presence of boron trifluoride diethyl etherate. Subsequent deprotection of 114 under mildly acidic conditions then furnished the labile chromophore (1). The synthetic route was readily modified for the preparation of singly and doubly (3)H- and (14)C-labeled 1, compounds unavailable by other means, for studies of the mechanism of action of neocarzinostatin in vivo.

Divergent chemo-, regio-, and diastereoselective normal electron-demand Povarov-type reactions with α-oxo-ketene dienophiles.

PubMed

Galvez, Jaime; Castillo, Juan-Carlos; Quiroga, Jairo; Rajzmann, Michel; Rodriguez, Jean; Coquerel, Yoann

2014-08-15

The reactions between electron-rich 2-aza-dienes and α-oxo-ketenes derived from the Wolff rearrangement of 2-diazocycloalkane-1,3-diones chemo- and regioselectively produced spiro hydropyrid-4-ones with good to excellent diastereoselectivities. These reactions are likely to proceed via a domino Wolff/Friedel-Crafts/intramolecular Mannich process. Prolonged domino sequences also allowed the expeditious preparation of a series of pyrazolopyridine and pyridopyrimidine heterocycles.

Synthesis and Purification of Iodoaziridines Involving Quantitative Selection of the Optimal Stationary Phase for Chromatography

PubMed Central

Boultwood, Tom; Affron, Dominic P.; Bull, James A.

2014-01-01

The highly diastereoselective preparation of cis-N-Ts-iodoaziridines through reaction of diiodomethyllithium with N-Ts aldimines is described. Diiodomethyllithium is prepared by the deprotonation of diiodomethane with LiHMDS, in a THF/diethyl ether mixture, at -78 °Cin the dark. These conditions are essential for the stability of the LiCHI2 reagent generated. The subsequent dropwise addition of N-Ts aldimines to the preformed diiodomethyllithium solution affords an amino-diiodide intermediate, which is not isolated. Rapid warming of the reaction mixture to 0 °C promotes cyclization to afford iodoaziridines with exclusive cis-diastereoselectivity. The addition and cyclization stages of the reaction are mediated in one reaction flask by careful temperature control. Due to the sensitivity of the iodoaziridines to purification, assessment of suitable methods of purification is required. A protocol to assess the stability of sensitive compounds to stationary phases for column chromatography is described. This method is suitable to apply to new iodoaziridines, or other potentially sensitive novel compounds. Consequently this method may find application in range of synthetic projects. The procedure involves firstly the assessment of the reaction yield, prior to purification, by 1H NMR spectroscopy with comparison to an internal standard. Portions of impure product mixture are then exposed to slurries of various stationary phases appropriate for chromatography, in a solvent system suitable as the eluent in flash chromatography. After stirring for 30 min to mimic chromatography, followed by filtering, the samples are analyzed by 1H NMR spectroscopy. Calculated yields for each stationary phase are then compared to that initially obtained from the crude reaction mixture. The results obtained provide a quantitative assessment of the stability of the compound to the different stationary phases; hence the optimal can be selected. The choice of basic alumina, modified to activity IV, as a suitable stationary phase has allowed isolation of certain iodoaziridines in excellent yield and purity. PMID:24893769

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

PubMed Central

Engelen, Bernward; Panthöfer, Martin; Deiseroth, Hans-Jörg; Schlirf, Jens

2016-01-01

Summary A one-pot transformation, which involves the reaction of ketones with aldehydes in the presence of metal halides to furnish tetrahydro-2H-pyran-2,4-diols in a highly diastereoselective manner, is investigated thoroughly by experiments and computations. The reaction was also successfully implemented on a flow micro reactor system. PMID:27340472

Synthetic Methods for Ester Bond Formation and Conformational Analysis of Ester-Containing Carbohydrates

NASA Astrophysics Data System (ADS)

Hackbusch, Sven

This dissertation encompasses work related to synthetic methods for the formation of ester linkages in organic compounds, as well as the investigation of the conformational influence of the ester functional group on the flexibility of inter-saccharide linkages, specifically, and the solution phase structure of ester-containing carbohydrate derivatives, in general. Stereoselective reactions are an important part of the field of asymmetric synthesis and an understanding of their underlying mechanistic principles is essential for rational method development. Here, the exploration of a diastereoselective O-acylation reaction on a trans-2-substituted cyclohexanol scaffold is presented, along with possible reasons for the observed reversal of stereoselectivity dependent on the presence or absence of an achiral amine catalyst. In particular, this work establishes a structure-activity relationship with regard to the trans-2-substituent and its role as a chiral auxiliary in the reversal of diastereoselectivity. In the second part, the synthesis of various ester-linked carbohydrate derivatives, and their conformational analysis is presented. Using multidimensional NMR experiments and computational methods, the compounds' solution-phase structures were established and the effect of the ester functional group on the molecules' flexibility and three-dimensional (3D) structure was investigated and compared to ether or glycosidic linkages. To aid in this, a novel Karplus equation for the C(sp2)OCH angle in ester-linked carbohydrates was developed on the basis of a model ester-linked carbohydrate. This equation describes the sinusoidal relationship between the C(sp2)OCH dihedral angle and the corresponding 3JCH coupling constant that can be determined from a J-HMBC NMR experiment. The insights from this research will be useful in describing the 3D structure of naturally occurring and lab-made ester-linked derivatives of carbohydrates, as well as guiding the de novo-design of carbohydrate based compounds with specific shape constraints for its use as enzyme inhibitors or similar targets. In addition, the above project led to the development of a methodology for the synthesis of symmetrical ester molecules from primary alcohols using a mild oxidative esterification reaction, which proceeds in hydrous solvents using a nitrosyl radical catalyst. The reaction could be performed with a variety of alcohols and the resulting compounds are of interest in the fragrance and flavor industries.

Photometric Characterization of the Reductive Amination Scope of the Imine Reductases from Streptomyces tsukubaensis and Streptomyces ipomoeae.

PubMed

Matzel, Philipp; Krautschick, Lukas; Höhne, Matthias

2017-10-18

Imine reductases (IREDs) have emerged as promising enzymes for the asymmetric synthesis of secondary and tertiary amines starting from carbonyl substrates. Screening the substrate specificity of the reductive amination reaction is usually performed by time-consuming GC analytics. We found two highly active IREDs in our enzyme collection, IR-20 from Streptomyces tsukubaensis and IR-Sip from Streptomyces ipomoeae, that allowed a comprehensive substrate screening with a photometric NADPH assay. We screened 39 carbonyl substrates combined with 17 amines as nucleophiles. Activity data from 663 combinations provided a clear picture about substrate specificity and capabilities in the reductive amination of these enzymes. Besides aliphatic aldehydes, the IREDs accepted various cyclic (C 4 -C 8 ) and acyclic ketones, preferentially with methylamine. IR-Sip also accepted a range of primary and secondary amines as nucleophiles. In biocatalytic reactions, IR-Sip converted (R)-3-methylcyclohexanone with dimethylamine or pyrrolidine with high diastereoselectivity (>94-96 % de). The nucleophile acceptor spectrum depended on the carbonyl substrate employed. The conversion of well-accepted substrates could also be detected if crude lysates were employed as the enzyme source. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A General Diastereoselective Catalytic Vinylogous Aldol Reaction Among Tetramic Acid-Derived Pyrroles

PubMed Central

2015-01-01

A catalytic diastereoselective aldol reaction has been developed for N1-arylated/C2-O-silylated/C3-methylated and brominated/C4-O-methylated pyrroles in its reactions with various aldehydes. Syn adducts emerge with regard to the vicinal nitrogen and oxygen heteroatom substituents. The N1-aryl residue undergoes oxidative cleavage, and the C3-bromine atom undergoes palladium-mediated coupling reactions, both without disturbing the newly created stereocenters. PMID:25119431

Efficient Synthesis of Differentiated syn-1,2-Diol Derivatives by Asymmetric Transfer Hydrogenation-Dynamic Kinetic Resolution of α-Alkoxy-Substituted β-Ketoesters.

PubMed

Monnereau, Laure; Cartigny, Damien; Scalone, Michelangelo; Ayad, Tahar; Ratovelomanana-Vidal, Virginie

2015-08-10

Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α-alkoxy-β-ketoesters in the presence of well-defined, commercially available, chiral catalyst Ru(II) -(N-p-toluenesulfonyl-1,2-diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α-alkoxy-β-hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of Ru(II) - and Rh(III) -tethered precatalysts extended this process to more-challenging substrates that bore alkenyl-, alkynyl-, and alkyl substituents to provide the corresponding syn α-alkoxy-β-hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)-propanoate, which is an important pharmacophore in a number of peroxisome proliferator-activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type-II diabetes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalytic Enantioselective Cyclization and C3-Fluorination of Polyenes

PubMed Central

Cochrane, Nikki A.; Nguyen, Ha; Gagne, Michel R.

2013-01-01

(xylyl-phanephos)Pt2+ in combination with XeF2 mediates the consecutive diastereoselective cation-olefin cyclization/fluorination of polyene substrates. Isolated yields were typically in the 60s while enantioselectivies reached as high as 87%. The data are consistent with a stereoretentive fluorination of a P2Pt-alkyl cation intermediate. PMID:23282101

HIGHLY DIASTEREOSELECTIVE MICHAEL ADDITION OF FLAVANONE TO ITS CHALCONE PRECURSOR UNDER SOLVENT-FREE CONDITIONS USING MICROWAVES

EPA Science Inventory

Substituted 2'-hydroxychalcones were found to give an equilibrium mixture of the starting chalcone and the corresponding flavanone in 4:6 - 1:3 ratio in the presence of various supports and MW irradiation. MW irradiation of 2'-hydroxychalcones in the presence of DBU gave two hit...

Chiral transcription in self-assembled tetrahedral Eu 4L 6 chiral cages displaying sizable circularly polarized luminescence

DOE PAGES

Yeung, Chi -Tung; Yim, King -Him; Wong, Ho -Yin; ...

2017-10-24

Predictable stereoselective formation of supramolecular assembly is generally believed to be an important but complicated process. Here, we show that point chirality of a ligand decisively influences its supramolecular assembly behavior. We designed three closely related chiral ligands with different point chiralities, and observe their self-assembly into europium (Eu) tetrametallic tetrahedral cages. One ligand exhibits a highly diastereoselective assembly into homochiral (either ΔΔΔΔ or ΛΛΛΛ) Eu tetrahedral cages whereas the two other ligands, with two different approaches of loosened point chirality, lead to a significant breakdown of the diastereoselectivity to generate a mixture of (ΔΔΔΔ and ΛΛΛΛ) isomers. The cagesmore » are highly emissive (luminescence quantum yields of 16(1) to 18(1)%) and exhibit impressive circularly polarized luminescence properties (|g lum |: up to 0.16). With in-depth studies, we present an example that correlates the nonlinear enhancement of the chiroptical response to the nonlinearity dependence on point chirality.« less

Diastereoselective syntheses of 3-aryl-5-(arylalkyl)-6-methyl-1-(1-phenylethyl)thioxotetrahydropyrimidin-4(1H)-ones: a stereochemical perspective from endo and exocyclic chiral centres.

PubMed

Kumar, Varun; Raghavaiah, Pallepogu; Mobin, Shaikh M; Nair, Vipin A

2010-11-07

Diastereoselective syntheses of 3-aryl-(S/R)-6-methyl-1-[(S/R)-1-phenylethyl)]-2-thioxotetrahydro pyrimidin-4(1H)-ones were achieved in good yields by the condensation of aryl isothiocyanates with ethyl 3-(1-phenylethylamino)butanoate in a one-pot reaction. Benzylation of these substrates illustrated that the orientations of the exocylic and endocylic groups determine the stereochemical outcome of the product formed.

Diastereoselective cyclization of an aminobenzoic acid derivative and chiroptical properties of triple-stranded helical bis(phenylethynyl)benzene.

PubMed

Yamakado, Ryohei; Matsuoka, Shin-ichi; Suzuki, Masato; Takeuchi, Daisuke; Masu, Hyuma; Azumaya, Isao; Takagi, Koji

2015-04-04

The diastereoselective cyclization of 2,5-dibromo-4-hexylaminobenzoic acid was achieved by the microwave-assisted condensation using SiCl4. Moreover, the triple-stranded helical structure of bis(phenylethynyl)benzene units embedded in the cyclic tri(benzamide) scaffold was obtained by a Sonogashira-Hagihara coupling reaction. Two optically active enantiomers that do not racemize even at the elevated temperature were separated by chiral HPLC. The chiral helical topology was revealed by the spectroscopic data and theoretical calculation.

Reverse the diastereoselectivity of the Rh(I)-catalyzed Pauson-Khand cycloaddition.

PubMed

Turlington, Mark; Pu, Lin

2011-08-19

It is discovered that the diastereoselectivity of the Rh(I)-catalyzed Pauson-Khand cycloaddition of chiral enynes can be reversed to generate the trans diastereomer as the major product in the absence of a chelate phosphine ligand when the substrate contains an appropriate functional group capable of chelate coordination to the Rh(I) center. This expands the application of the Rh(I)-based catalytic processes to prepare both the cis and trans stereoisomers. © 2011 American Chemical Society

Diastereoselective intermolecular Pauson-Khand reactions of chiral cyclopropenes.

PubMed

Pallerla, Mahesh K; Fox, Joseph M

2005-08-04

In this Letter, it is demonstrated that the unusual reactivity of cyclopropenes can increase the scope and utility of intermolecular Pauson-Khand reactions. The well-defined chiral environment of cyclopropenes has a powerful influence on the diastereoselectivity of the reactions and leads to the production of a single cyclopentenone in each of the described cases. The cyclopropane ring strongly influences the stereochemistry of reactions at the enone, and the three-membered ring can subsequently be cleaved under mild conditions. [reaction: see text

Diastereoselective chain-elongation reactions using microreactors for applications in complex molecule assembly.

PubMed

Carter, Catherine F; Lange, Heiko; Sakai, Daiki; Baxendale, Ian R; Ley, Steven V

2011-03-14

Diastereoselective chain-elongation reactions are important transformations for the assembly of complex molecular structures, such as those present in polyketide natural products. Here we report new methods for performing crotylation reactions and homopropargylation reactions by using newly developed low-temperature flow-chemistry technology. In-line purification protocols are described, as well as the application of the crotylation protocol in an automated multi-step sequence. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biferrocene-Based Diphosphine Ligands: Synthesis and Application of Walphos Analogues in Asymmetric Hydrogenations

PubMed Central

2013-01-01

A total of four biferrocene-based Walphos-type ligands have been synthesized, structurally characterized, and tested in the rhodium-, ruthenium- and iridium-catalyzed hydrogenation of alkenes and ketones. Negishi coupling conditions allowed the biferrocene backbone of these diphosphine ligands to be built up diastereoselectively from the two nonidentical and nonracemic ferrocene fragments (R)-1-(N,N-dimethylamino)ethylferrocene and (SFc)-2-bromoiodoferrocene. The molecular structures of (SFc)-2-bromoiodoferrocene, the coupling product, two ligands, and the two complexes ([PdCl2(L)] and [RuCl(p-cymene)(L)]PF6) were determined by X-ray diffraction. The structural features of complexes and the catalysis results obtained with the newly synthesized biferrocene-based ligands were compared with those of the corresponding Walphos ligands. PMID:23457421

Design and Synthesis of a Library of Tetracyclic Hydroazulenoisoindoles

PubMed Central

Brummond, Kay M.; Mao, Shuli; Shinde, Sunita N.; Johnston, Paul J.; Day, Billy W.

2009-01-01

Forty-four tetracyclic hydroazulenoisoindoles were synthesized via a tandem cyclopropanation/Cope rearrangement followed by a Diels-Alder sequence from easily available five-membered cyclic cross-conjugated trienones. These trienones were obtained from two different routes depending upon whether R1 and R2 are alkyl or amino acid derived functional groups, via a rhodium(I)-catalyzed cycloisomerization reaction. In order to increase diversity, four maleimides and two 1,2,4-triazoline-3,5-diones were used as dienophiles in the Diels-Alder step. Several Diels-Alder adducts were further reacted under palladium-catalyzed hydrogenation conditions, leading to a diastereoselective reduction of the trisubstituted double bond. This library has demonstrated rapid access to a variety of structurally complex natural product-like compounds via stereochemical diversity and building block diversity approaches. PMID:19366169

Total synthesis of dihydrolysergic acid and dihydrolysergol: development of a divergent synthetic strategy applicable to rapid assembly of D-ring analogs.

PubMed

Lee, Kiyoun; Poudel, Yam B; Glinkerman, Christopher M; Boger, Dale L

2015-09-02

The total syntheses of dihydrolysergic acid and dihydrolysergol are detailed based on a Pd(0)-catalyzed intramolecular Larock indole cyclization for the preparation of the embedded tricyclic indole (ABC ring system) and a subsequent powerful inverse electron demand Diels-Alder reaction of 5-carbomethoxy-1,2,3-triazine with a ketone-derived enamine for the introduction of a functionalized pyridine, serving as the precursor for a remarkably diastereoselective reduction to the N -methylpiperidine D-ring. By design, the use of the same ketone-derived enamine and a set of related complementary heterocyclic azadiene [4 + 2] cycloaddition reactions permitted the late stage divergent preparation of a series of alternative heterocyclic derivatives not readily accessible by more conventional approaches.

Silylative Reductive Amination of α,β-Unsaturated Aldehydes: A Convenient Synthetic Route to β-Silylated Secondary Amines.

PubMed

Kim, Eunae; Park, Sehoon; Chang, Sukbok

2018-04-17

Described here is a reductive amination/hydrosilylation cascade of α,β-unsaturated aldehydes mediated by a Lewis acidic borane catalyst. The present reaction system provides an one-pot synthetic route towards β-silylated secondary amines that have not been accessible by other previous catalysis. Comparative 1 H NMR studies on the silylative reduction of enimines revealed that steric bulkiness of primary amine reactants strongly affects both catalytic efficiency and regioselectivity. This strategy was applicable to a broad range of substrates and amenable to one-pot gram-scale synthesis. Moreover, a diastereoselective introduction of the β-silyl group was also found to be feasible (d.r. up to 71:29). © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Catalyst–Controlled C–O versus C–N Allylic Functionalization of Terminal Olefins

PubMed Central

Strambeanu, Iulia I.; White, M. Christina

2014-01-01

The divergent synthesis of syn-1, 2-aminoalcohol or syn-1,2-diamine precursors from a common terminal olefin has been accomplished using a combination of palladium(II) catalysis with Lewis acid co-catalysis. Palladium(II)/bis-sulfoxide catalysis with a silver triflate co-catalyst leads for the first time to anti-2-aminooxazolines (C—O) in good to excellent yields. Simple removal of the bis-sulfoxide ligand from this reaction results in a complete switch in reactivity to afford anti-imidazolidinone products (C—N) in good yields and excellent diastereoselectivities. Mechanistic studies suggest the divergent C—O versus C—N reactivity from a common ambident nucleophile arises due to a switch in mechanism from allylic C—H cleavage/functionalization to olefin isomerization/oxidative amination. PMID:23855956

Diastereoselective synthesis of ethyl ( Z)-3-(8-methylimidazo-[1,2- a]pyrid-2-yl)-2-phenylthioacrylate. X-ray crystal structure and conformational analysis

NASA Astrophysics Data System (ADS)

Gautier, A.; Roche, D.; Métin, J.; Carpy, A.; Madesclaire, M.

1995-09-01

The title compound 2, a gem vinyl sulfide ester, has been obtained diastereoselectively (de > 98%) by action of the ethyl thiophenoxyacetate carbanion on the imidazo[1,2- a]pyridinecarbaldehyde 1 in a basic medium, at low temperature. The X-ray crystal structure of 2 (C 19H 19N 2O 2S: Mr = 338.43, triclinic, P 1¯, a = 8.193(3) Å, b = 10.090(2) Å, c = 10.981(4) Å, α = 88.12(2)°, β = 78.66(4)°, γ = 78.53(2)°, V = 872.3(6) Å3, Z = 2, Dcalc = 1.29 g cm -3, λ( Mo Kα) = 0.71069 Å, μ = 0.189 mm -1, F(000) = 356, T = 293 K, R = 0.043 for 3610 observed reflections) has been determined and confirmed the Z configuration. The molecule is almost planar except for the phenyl ring situated in an approximate perpendicular plane. Despite the presence of the conjugate double bonds of the vinyl ester group (acrylate), coplanar with the imidazopyridine heterocycle, there is no evidence of π-electron delocalization over the whole structure. The crystal cohesion is ensured by a dense network of van der Waals contacts. A conformational analysis of the Z and E isomers by means of a Monte Carlo search and a stochastic dynamics simulation in CHCl 3 has shown that according to the method the Z isomer is more stable than the E isomer by about 7 to 10 kJ mol -1.

Callipeltosides A, B and C: Total Syntheses and Structural Confirmation

PubMed Central

Frost, James R; Pearson, Colin M; Snaddon, Thomas N; Booth, Richard A; Turner, Richard M; Gold, Johan; Shaw, David M; Gaunt, Matthew J; Ley, Steven V

2015-01-01

Since their isolation almost 20 years ago, the callipeltosides have been of long standing interest to the synthetic community owing to their unique structural features and inherent biological activity. Herein we present our full research effort that has led to the synthesis of these molecules. Key aspects of our final strategy include 1) synthesis of the C1–C9 pyran core (5) using an AuCl3-catalysed cyclisation; 2) formation of C10–C22 vinyl iodide (55) by sequential bidirectional Stille reactions and 3) diastereoselective union of these advanced fragments by means of an alkenylzinc addition (d.r.=91:9 at C9). The common callipeltoside aglycon (4) was completed in a further five steps. Following this, all three sugar fragments were appended to provide the entire callipeltoside family. In addition to this, D-configured callipeltose B was synthesised and appended to the callipeltoside aglycon. The 1H NMR spectrum of this molecule was found to be significantly different to the natural isolate, further supporting our assignment of callipeltoside B (2). PMID:26230615

[Development of boomerang-type intramolecular cascade reactions and application to natural product synthesis].

PubMed

Takasu, K

2001-12-01

Intramolecular cascade reaction has received much attention as a powerful methodology to construct a polycyclic framework in organic synthesis. We have been developing "boomerang-type cascade reaction" to construct a variety of polycyclic skeletons efficiently. In the above reactions, a nucleophilic function of substrates changes the character into an electrophile after the initial reaction, and the electrophilic group acts as a nucleophile in the second reaction. That is, the reaction center stepwise moves from one functional group back to the same one via other functional groups. The stream of the electron concerning the cascade reaction is like a locus of boomerang. We show here three different boomerang-type reactions via ionic species or free radicals. 1) Diastereoselective Michael-aldol reaction based on the chiral auxiliary method and enantioselective Michael-aldol reaction by the use of external chiral sources. 2) Short and efficient total syntheses of longifolane sesquiterpenes utilizing intramolecular double Michael addition as a key step. 3) Development of boomerang-type radical cascade reaction of halopolyenes to construct terpenoid skeletons and its regioselectivity.

Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.

PubMed

Siegel, Dustin; Hui, Hon C; Doerffler, Edward; Clarke, Michael O; Chun, Kwon; Zhang, Lijun; Neville, Sean; Carra, Ernest; Lew, Willard; Ross, Bruce; Wang, Queenie; Wolfe, Lydia; Jordan, Robert; Soloveva, Veronica; Knox, John; Perry, Jason; Perron, Michel; Stray, Kirsten M; Barauskas, Ona; Feng, Joy Y; Xu, Yili; Lee, Gary; Rheingold, Arnold L; Ray, Adrian S; Bannister, Roy; Strickley, Robert; Swaminathan, Swami; Lee, William A; Bavari, Sina; Cihlar, Tomas; Lo, Michael K; Warren, Travis K; Mackman, Richard L

2017-03-09

The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC 50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.

Diastereoselective Carbocyclization of 1,6-Heptadienes Triggered by Rhodium-Catalyzed Activation of an Olefinic C=H Bond**

PubMed Central

Aïssa, Christophe; Ho, Kelvin Y T; Tetlow, Daniel J; Pin-Nó, María

2014-01-01

The use of α,ω-dienes as functionalization reagents for olefinic carbon–hydrogen bonds has been rarely studied. Reported herein is the rhodium(I)-catalyzed rearrangement of prochiral 1,6-heptadienes into [2,2,1]-cycloheptane derivatives with concomitant creation of at least three stereogenic centers and complete diastereocontrol. Deuterium-labeling studies and the isolation of a key intermediate are consistent with a group-directed C=H bond activation, followed by two consecutive migratory insertions, with only the latter step being diastereoselective. PMID:24634225

A Diastereoselective Multicomponent Reaction for Construction of Alkynylamide-Substituted α,β-Diamino Acid Derivatives To Hunt Hits.

PubMed

Lei, Ruirui; Wu, Yong; Dong, Suzhen; Jia, Kaili; Liu, Shunying; Hu, Wenhao

2017-03-17

A highly diasetereoselective Mannich-type multicomponent reaction was developed to rapidly construct alkynylamide-substituted α,β-diamino acid derivatives from simple starting materials under mild conditions in moderate to good yields for hit hunting. Most of the resulting products 4 exhibited good anticancer activity in HCT116, BEL7402, and SMMC7721 cells.

Control of diastereoselectivity by solvent effects in the addition of Grignard reagents to enantiopure t-butylsulfinimine: syntheses of the stereoisomers of the hydroxyl derivatives of sibutramine.

PubMed

Lu, Bruce Z; Senanayake, Chris; Li, Nansheng; Han, Zhengxu; Bakale, Roger P; Wald, Stephen A

2005-06-23

[reaction: see text] An efficient method has been developed to prepare all four isomers of the hydroxyl derivatives of sibutramine by addition of Grignard reagents (R)- or (S)-5 to a single enantiomer of sulfinyl imine (R)-1 simply by tuning the reaction solvent. The phenomenon of the reversed diastereoselectivity in CH(2)Cl(2) and THF implied that the reaction may proceed through a chelated cyclic transition state in CH(2)Cl(2) and nonchelated acyclic transition state in THF.

Diastereoselective Diels-Alder reactions of alpha-fluorinated alpha,beta-unsaturated carbonyl compounds: chemical consequences of fluorine substitution. 2.

PubMed

Essers, Michael; Mück-Lichtenfeld, Christian; Haufe, Günter

2002-07-12

Two alpha-fluoro alpha,beta-unsaturated carbonyl compounds, i.e., benzyl 2-fluoroacrylate (3) and 2-fluorooct-1-en-3-one (4), as well as the corresponding nonfluorinated parent compounds, were synthesized and subjected to Diels-Alder reactions with cyclopentadiene. The cycloadditions were conducted thermally, microwave-assisted, and Lewis acid-mediated (TiCl(4)). The fluorinated dienophiles exhibited a lower reactivity and exo diastereoselectivity, while the corresponding nonfluorinated parent compounds reacted endo selectively. DFT calculations suggest that kinetic effects of fluorine determine the stereoselectivity rather than higher thermodynamic stability of the exo products.

A new reactivity mode for the diazo group: diastereoselective 1,3-aminoalkylation reaction of β-amino-α-diazoesters to give triazolines.

PubMed

Kuznetsov, Alexey; Gulevich, Anton V; Wink, Donald J; Gevorgyan, Vladimir

2014-08-18

A novel mode of reactivity for the diazo group, the 1,3-addition of a nucleophile and an electrophile to the diazo group, has been realized in the intramolecular aminoalkylation of β-amino-α-diazoesters to form tetrasubstituted 1,2,3-triazolines. The reaction exhibited a broad scope, good functional group tolerance, and excellent diastereoselectivity. In addition, a new Au-catalyzed intramolecular transannulation reaction of the obtained propargyl triazolines to give pyrroles has been discovered. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly Stereoselective Intermolecular Haloetherification and Haloesterification of Allyl Amides

PubMed Central

Soltanzadeh, Bardia; Jaganathan, Arvind; Staples, Richard J.

2016-01-01

An organocatalytic and highly regio-, diastereo-, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio- and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification. PMID:26110812

Highly selective rhodium catalyzed domino C-H activation/cyclizations.

PubMed

Trans, Duc N; Cramer, Nicolai

2011-01-01

The direct functionalization of carbon-hydrogen bonds is an emerging tool to establish more sustainable and efficient synthetic methods. We present its implementation in a cascade reaction that provides a rapid assembly of functionalized indanylamines from simple and readily available starting materials. Careful choice of the ancillary ligand---an electron-rich bidentate phosphine ligand--enables highly diastereoselective rhodium(i)-catalyzed intramolecular allylations of unsubstituted ketimines induced by a directed C-H bond activation and allene carbo-metalation sequence.

Aqueous organometallic chemistry. 2. {sup 1}H NMR spectroscopic, synthetic, and structural study of the chemo- and diastereoselective reactions of [Cp{sup *}Rh(H{sub 2}O){sub 3}]{sup 2+} with nitrogen ligands as a function of pH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogo, Seiji; Chen, H.; Fish, R.H.

The reactions of a new Cp{sup *}Rh aqua synthon, [Cp{sup *}Rh(H{sub 2}O){sub 3}]{sup 2+} (1), at acidic pH values (2-6) with aniline (2), pyridine (3), and L-phenylalanine (4) have provided interesting chemo- and diastereoselectivities as studied by {sup 1}H NMR, FAB/MS, and single-crystal X-ray crystallography. The reaction of 2 and aqua complex 1, at pH values from 4 to 6, quantitatively provided [Cp{sup *}Rh({eta}{sup 6}-aniline)]{sup 2+} (5); the structure of 5 was unequivocally determined by a single-crystal X-ray analysis, which also showed an approximate 25% {eta}{sup 5} component. Compound 3 reacted with 1, at pH 2-6, to selectively provide [Cp{supmore » *}Rh({eta}{sup 1}-pyridine){sub n} (H{sub 2}O){sub 3-n}]{sup 2+} (n = 1-3) complexes 6a-c as a function of pH. Surprisingly, complex 1 reacted with 4, from pH 4 to 6, to provide only one diastereomer of the known cyclic trimer [(Cp{sup *}Rh)({mu}-{eta}{sup 1}-(OCO):{eta}{sup 2}-(N,OCO)-L-phe nylalanine)]{sub 3}{sup 3+} (7; S{sub C},S{sub C},S{sub C},S{sub Rh},S{sub Rh},S{sub Rh},) an example of a one-step, highly diastereoselective reaction in H{sub 2}O. 8 refs., 4 figs., 2 tabs.« less

Dynamic kinetic asymmetric cross-benzoin additions of β-stereogenic α-keto esters.

PubMed

Goodman, C Guy; Johnson, Jeffrey S

2014-10-22

The dynamic kinetic resolution of β-halo α-keto esters via an asymmetric cross-benzoin reaction is described. A chiral N-heterocyclic carbene catalyzes the umpolung addition of aldehydes to racemic α-keto esters. The resulting fully substituted β-halo glycolic ester products are obtained with high levels of enantio- and diastereocontrol. The high chemoselectivity observed is a result of greater electrophilicity of the α-keto ester toward the Breslow intermediate. The reaction products are shown to undergo highly diastereoselective substrate-controlled reduction to give highly functionalized stereotriads.

Dynamic Kinetic Asymmetric Cross-Benzoin Additions of β-Stereogenic α-Keto Esters

PubMed Central

2015-01-01

The dynamic kinetic resolution of β-halo α-keto esters via an asymmetric cross-benzoin reaction is described. A chiral N-heterocyclic carbene catalyzes the umpolung addition of aldehydes to racemic α-keto esters. The resulting fully substituted β-halo glycolic ester products are obtained with high levels of enantio- and diastereocontrol. The high chemoselectivity observed is a result of greater electrophilicity of the α-keto ester toward the Breslow intermediate. The reaction products are shown to undergo highly diastereoselective substrate-controlled reduction to give highly functionalized stereotriads. PMID:25299730

Novel Applications of Donor-Acceptor Cyclopropanes and Dearomatization towards the Expedient Synthesis of Highly Substituted Carbocycles

NASA Astrophysics Data System (ADS)

Mackay, William Daniel

I. Lewis Acid Catalyzed (3+2)-Annulations of Donor-Acceptor Cyclopropanes and Ynamides. The Sc(OTf)3-catalyzed (3+2)-annulation of donor-acceptor cyclopropanes and ynamides is described, providing the corresponding cyclopentene sulfonamides in good to excellent yield. Deprotection and hydrolysis of the resulting cyclopentenesulfonamides delivers 2,3-substituted cyclopentanones with high diastereoselectivity. II. Kinetic Separation and Asymmetric Reactions of Norcaradiene Cycloadducts: Facilitated Access via H2O-Accelerated Cycloaddition. We exploit the Buchner reaction to access 1,2-disubstituted cyclohexadiene synthons (norcaradienes), which participate in H2O-accelerated cycloaddition with dienophiles to provide cyclopropyl-fused [2.2.2]-bicyclooctene derivatives in good yields. Regioisomeric mixtures can be kinetically separated exploiting different reaction rates in Diels-Alder reactions. meso -Diels-Alder products may be enantioselectively desymmetrized, providing highly substituted cyclohexanes with up to seven contiguous stereocenters. III. The Development of Regioisomerically Enriched Buchner Products for Use as Cyclohexadienyl Synthetic Intermediates. We have investigated two conceptual methods to generate highly regioisomerically enriched norcaradienyl intermediates through arene cyclopropanation. Intermolecular Buchner reaction of aryl diazoacetates under either thermolysis or silver(I) catalysis provide expedient routes to single regioisomeric norcaradienes, in some cases favoring the least sterically encumbered site of cyclopropanation. Intramolecular Buchner reaction of benzyl cyanodiazoacetates allow for the site-selective cyclopropanation of the tethered arene, and the installation of an activated cyclopropane for downstream functionalization. Both methods generate norcaradienes that are amenable to further transformations to generate highly stereochemically complex carbocyclic products.

Vinyl sulfoxides as stereochemical controllers in intermolecular Pauson-Khand reactions: applications to the enantioselective synthesis of natural cyclopentanoids.

PubMed

Rodríguez Rivero, Marta; Alonso, Inés; Carretero, Juan C

2004-10-25

The use of sulfoxides as chiral auxiliaries in asymmetric intermolecular Pauson-Khand reactions is described. After screening a wide variety of substituents on the sulfur atom in alpha,beta-unsaturated sulfoxides, the readily available o-(N,N-dimethylamino)phenyl vinyl sulfoxide (1 i) has proved to be highly reactive with substituted terminal alkynes under N-oxide-promoted conditions (CH3CN, 0 degrees C). In addition, these Pauson-Khand reactions occurred with complete regioselectivity and very high diastereoselectivity (de=86->96 %, (S,R(S)) diastereomer). Experimental studies suggest that the high reactivity exhibited by the vinyl sulfoxide 1 i relies on the ability of the amine group to act as a soft ligand on the alkyne dicobalt complex prior to the generation of the cobaltacycle intermediate. On the other hand, both theoretical and experimental studies show that the high stereoselectivity of the process is due to the easy thermodynamic epimerization at the C5 center in the resulting 5-sulfinyl-2-cyclopentenone adducts. When it is taken into account that the known asymmetric intermolecular Pauson-Khand reactions are limited to the use of highly reactive bicyclic alkenes, mainly norbornene and norbornadiene, this novel procedure constitutes the first asymmetric version with unstrained acyclic alkenes. As a demonstration of the synthetic interest of this sulfoxide-based methodology in the enantioselective preparation of stereochemically complex cyclopentanoids, we have developed very short and efficient syntheses of the antibiotic (-)-pentenomycin I and the (-)-aminocyclopentitol moiety of a hopane triterpenoid.

Stereogenic phosphorus-induced diastereoselective formation of chiral carbon during nucleophilic addition of chiral H-P species to aldehydes or ketones.

PubMed

Zhang, He; Sun, Yong-Ming; Yao, Lan; Ji, Si-Yu; Zhao, Chang-Qiu; Han, Li-Biao

2014-05-01

P,C-stereogenic α-hydroxyl phosphinates or phosphine oxides were prepared from the additions of (RP)-phosphinate to ketones or (RP)-phosphine oxide to aldehydes, respectively, catalyzed by bases at room temperature in up to >99:1 diasteromeric ratio (d.r.P/d.r.C) and 99 % yields. The diastereoselectivity was induced by reversible equilibrium and different stabilities between two diastereomers of adduct, which was caused by the spatial interaction between menthoxyl or menthyl to alkyl groups of aldehydes or ketones. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

From designer Lewis acid to designer Brønsted acid towards more reactive and selective acid catalysis

PubMed Central

YAMAMOTO, Hisashi

2008-01-01

This review focuses on the development of acid catalysis for selective organic transformations conducted in our laboratories for the past 30 years. Several important concepts in designing of catalysts are described with some examples. Further, recent developments in super Brønsted acid and their applications in a one-pot procedure to construct complex molecules with high diastereoselectivities are described. PMID:18941293

(3+3)-Annulation of Donor-Acceptor Cyclopropanes with Diaziridines.

PubMed

Trushkov, Igor V; Chagarovskiy, Alexey O; Vasin, Vladimir S; Kuznetsov, Vladimir V; Ivanova, Olga A; Rybakov, Victor B; Shumsky, Alexey N; Makhova, Nina N

2018-06-23

The first example of (3+3)-annulation of two different three-membered rings is reported herein. Donor-acceptor cyclopropanes in reaction with diaziridines were found to afford perhydropyridazine derivatives in high yields and diastereoselectivity under mild Lewis acid catalysis. The disclosed reaction is applicable for the broad substrate scope and exhibits an excellent functional group tolerance. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stereocontrolled Alkylative Construction of Quaternary Carbon Centers

PubMed Central

Kummer, David A.; Chain, William J.; Morales, Marvin R.; Quiroga, Olga; Myers, Andrew G.

2009-01-01

Protocols for the stereodefined formation of α,α-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of α,α-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine α-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the α-C-H bond with α-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common π-face of the E- and Z-enolates, proposed to be that opposite the pseudoephedrine alkoxide side-chain. Pseudoephedrine α-phenylbutyramides are found to undergo highly stereoselective but not stereospecific α-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that α, α-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an α-alkyl-α,β-unsaturated pseudoephedrine amide, providing α,α-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the α-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes. PMID:18788739

Diastereoselective preparation of (R)- and (S)-2-methoxy-2-phenylpent-3-ynoic acids and their use as reliable chiral derivatizing agents.

PubMed

Pérez-Estrada, Salvador; Joseph-Nathan, Pedro; Jiménez-Vázquez, Hugo A; Medina-López, Manuel E; Ayala-Mata, Francisco; Zepeda, L Gerardo

2012-02-17

Benzoyl-S,O-acetals 1a and 1b were used as chiral auxiliaries to achieve the diastereoselective preparation of both enantiomers of 2-methoxy-2-phenylpent-3-ynoic acids (MPPAs). The latter were condensed with several chiral secondary alcohols and some primary amines to evaluate their potential as chiral derivatizing agents (CDAs). The (1)H NMR spectra of the corresponding esters and amides showed strong consistency with the absolute configuration of the carbinol and amine moieties, whose observed ΔδL(1) and ΔδL(2) values were in the ranges of 0.1-0.4 and 0.02-0.12 ppm, respectively.

Origin of diastereoselectivity in the organolanthanide-mediated intramolecular hydroamination/cyclisation of aminodienes: a computational exploration of constrained geometry CGC-Ln catalysts.

PubMed

Tobisch, Sven

2007-01-01

The regulation of ring-substituent diastereoselectivity in the intramolecular hydroamination/cyclisation (IHC) of alpha-substituted aminodienes by constrained geometry CGC-lanthanide catalysts (CGC=[Me(2)Si(eta(5)-Me(4)C(5))(tBuN)](2-)) has been elucidated by means of a reliable DFT method. The first survey of relevant elementary steps for the 1-methyl-(4E,6)-heptadienylamine substrate (1) and the [{Me(2)Si(eta(5)-Me(4)C(5))(tBuN)}Sm{N(TMS)(2)}] starting material (2) identified the following general mechanistic aspects of Ln-catalysed aminodiene IHC. The substrate-adduct 3-S of the active CGC-Ln-amidodiene compound represents the catalyst's resting state, but the substrate-free form 3' with a chelating amidodiene functionality is the direct precursor for cyclisation. This step proceeds with almost complete regioselectivity through exocyclic ring closure by means of a frontal trajectory, giving rise to the CGC-Ln-azacycle intermediate 4. Subsequent protonolysis of 4 is turnover limiting, whilst the ring-substituent diastereoselectivity is dictated by exocyclic ring closure. Unfavourable close interatomic contacts between the substrate's alpha-substituent and the catalyst backbone have been shown to largely govern the trans/cis selectivity. Substituents of sufficient bulk in the alpha-position of the substrate have been identified as being vital for stereochemical induction. The present study has indicated that the diastereoselectivity of ring closure can be considerably modulated. The variation of the lanthanide's ionic radius and introduction of extra steric pressure at the substrate's alpha-position and/or the CGC N centre have been identified as effective handles for tuning the selectivity. The quantification of these factors reported herein represents the first step toward the rational design of improved CGC-Ln catalyst architectures and will thus aid this process.

Construction of a chiral central nervous system (CNS)-active aminotetralin drug compound based on a synthesis strategy using multitasking properties of (S)-1-phenylethylamine.

PubMed

Federsel, Hans-Jürgen; Hedberg, Martin; Qvarnström, Fredrik R; Sjögren, Magnus P T; Tian, Wei

2007-12-01

This Account describes the design and development of a scalable synthesis for the drug molecule AR-A2 (1) starting from the discovery route originating in medicinal chemistry. Special emphasis is placed on the introduction of the correct (R) stereochemistry on C2, which was ultimately achieved in a diastereoselective imine-reducing step applying NaBH4. After optimization, this transformation was operated on a large pilot-plant scale (2000 L), offering the desired product (11) in 55% yield and 96% diastereomeric excess at a 100 kg batch size. From a synthesis strategy point of view, the choice of (S)-1-phenylethylamine (9) was crucial not only for its role as a provider of the NH2 functionality and the stereo-directing abilities but also as an excellent protecting group in the subsequent N-arylation reaction, according to the Buchwald-Hartwig protocol. As one of the very first examples in its kind, the latter step was scaled up to pilot manufacturing (125 kg in 2500 L vessel size), delivering an outstanding isolated yield of 95%. This consecutive series of chemical transformations was completed with an environmentally friendly removal of the phenethyl appendage. In addition, an elegant method to synthesize the tetralone substrate 6, as well as a novel and robust procedure to use imidazole as a buffer for the selective formation of the mono-HBr salt of AR-A2, will be briefly described.

Synthetic approach to the AB ring system of ouabain.

PubMed

Jung, Michael E; Piizzi, Grazia

2003-04-04

Several novel hydroxylated cis-decalin derivatives, potential intermediates for the synthesis of the AB ring system of the important cardiotonic steroid ouabain, have been synthesized from commercially available starting materials. The first step in the preparation of these highly functionalized intermediates is a Robinson annulation of the beta-keto ester 6 and the 4-silyl-3-buten-2-one 5 to furnish the octalone 4 with good diastereoselectivity in fair yield (due to competition with a novel silicon-to-carbon phenyl migration). Reduction of the epoxy alcohol 3 (derived from 4 in two high-yielding steps) with LiAlH(4) gave a mixture of the desired triol 11 along with the product of an unusual reductive opening at the tertiary carbon, namely the triol 12. A plausible mechanism for this unusual reduction is presented as are possible methods for avoiding it. In particular, reduction of the corrresponding epoxy ketone 15 with aluminum amalgam proceeded in good yield to give the hydroxy ketone 16. Also reduction of the epoxide ester having the inverted stereochemistry at C3 afforded the desired tertiary alcohol 33 in good yield. Another approach using the beta,gamma-unsaturated ketal 38 permitted the formation of the tertiary alcohol 40. Fleming oxidation of the related, very functionalized silane 39 afforded the desired 1beta-alcohol 41 in fair yield. Finally a novel rearrangement was observed when the epoxy alcohol 24 was treated with DIBAL to effect loss of the angular hydroxymethyl group to produce the tetrasubstitued alkene 29 in high yield.

Diastereoselective Radical‐Type Cyclopropanation of Electron‐Deficient Alkenes Mediated by the Highly Active Cobalt(II) Tetramethyltetraaza[14]annulene Catalyst

PubMed Central

Chirila, Andrei; Gopal Das, Braja; Paul, Nanda D.

2017-01-01

Abstract A new protocol for the catalytic synthesis of cyclopropanes using electron‐deficient alkenes is presented, which is catalysed by a series of affordable, easy to synthesise and highly active substituted cobalt(II) tetraaza[14]annulenes. These catalysts are compatible with the use of sodium tosylhydrazone salts as precursors to diazo compounds in one‐pot catalytic transformations to afford the desired cyclopropanes in almost quantitative yields. The reaction takes advantage of the metalloradical character of the Co complexes to activate the diazo compounds. The reaction is practical and fast, and proceeds from readily available starting materials. It does not require the slow addition of diazo reagents or tosylhydrazone salts or heating and tolerates many solvents, which include protic ones such as MeOH. The CoII complexes derived from the tetramethyltetraaza[14]annulene ligand are easier to prepare than cobalt(II) porphyrins and present a similar catalytic carbene radical reactivity but are more active. The reaction proceeds at 20 °C in a matter of minutes and even at −78 °C in a few hours. The catalytic system is robust and can operate with either the alkene or the diazo reagent as the limiting reagent, which inhibits the dimerisation of diazo compounds totally. The protocol has been applied to synthesise a variety of substituted cyclopropanes. High yields and selectivities were achieved for various substrates with an intrinsic preference for trans cyclopropanes. PMID:28529668

Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA) derivatives: key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease.

PubMed

Beaulieu, Pierre L; Gillard, James; Bailey, Murray D; Boucher, Colette; Duceppe, Jean-Simon; Simoneau, Bruno; Wang, Xiao-Jun; Zhang, Li; Grozinger, Karl; Houpis, Ioannis; Farina, Vittorio; Heimroth, Heidi; Krueger, Thomas; Schnaubelt, Jürgen

2005-07-22

(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.

Highly productive CNN pincer ruthenium catalysts for the asymmetric reduction of alkyl aryl ketones.

PubMed

Baratta, Walter; Chelucci, Giorgio; Magnolia, Santo; Siega, Katia; Rigo, Pierluigi

2009-01-01

Chiral pincer ruthenium complexes of formula [RuCl(CNN)(Josiphos)] (2-7; Josiphos = 1-[1-(dicyclohexylphosphano)ethyl]-2-(diarylphosphano)ferrocene) have been prepared by treating [RuCl(2)(PPh(3))(3)] with (S,R)-Josiphos diphosphanes and 1-substituted-1-(6-arylpyridin-2-yl)methanamines (HCNN; substituent = H (1 a), Me (1 b), and tBu (1 c)) with NEt(3). By using 1 b and 1 c as a racemic mixture, complexes 4-7 were obtained through a diastereoselective synthesis promoted by acetic acid. These pincer complexes, which display correctly matched chiral PP and CNN ligands, are remarkably active catalysts for the asymmetric reduction of alkyl aryl ketones in basic alcohol media by both transfer hydrogenation (TH) and hydrogenation (HY), achieving enantioselectivities of up to 99 %. In 2-propanol, the enantioselective TH of ketones was accomplished by using a catalyst loading as low as 0.002 mol % and afforded a turnover frequency (TOF) of 10(5)-10(6) h(-1) (60 and 82 degrees C). In methanol/ethanol mixtures, the CNN pincer complexes catalyzed the asymmetric HY of ketones with H(2) (5 atm) at 0.01 mol % relative to the complex with a TOF of approximately 10(4) h(-1) at 40 degrees C.

Sequence-Dependent Diastereospecific and Diastereodivergent Crosslinking of DNA by Decarbamoylmitomycin C.

PubMed

Aguilar, William; Paz, Manuel M; Vargas, Anayatzinc; Clement, Cristina C; Cheng, Shu-Yuan; Champeil, Elise

2018-04-20

Mitomycin C (MC), a potent antitumor drug, and decarbamoylmitomycin C (DMC), a derivative lacking the carbamoyl group, form highly cytotoxic DNA interstrand crosslinks. The major interstrand crosslink formed by DMC is the C1'' epimer of the major crosslink formed by MC. The molecular basis for the stereochemical configuration exhibited by DMC was investigated using biomimetic synthesis. The formation of DNA-DNA crosslinks by DMC is diastereospecific and diastereodivergent: Only the 1''S-diastereomer of the initially formed monoadduct can form crosslinks at GpC sequences, and only the 1''R-diastereomer of the monoadduct can form crosslinks at CpG sequences. We also show that CpG and GpC sequences react with divergent diastereoselectivity in the first alkylation step: 1"S stereochemistry is favored at GpC sequences and 1''R stereochemistry is favored at CpG sequences. Therefore, the first alkylation step results, at each sequence, in the selective formation of the diastereomer able to generate an interstrand DNA-DNA crosslink after the "second arm" alkylation. Examination of the known DNA adduct pattern obtained after treatment of cancer cell cultures with DMC indicates that the GpC sequence is the major target for the formation of DNA-DNA crosslinks in vivo by this drug. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineering Cofactor Preference of Ketone Reducing Biocatalysts: A Mutagenesis Study on a γ-Diketone Reductase from the Yeast Saccharomyces cerevisiae Serving as an Example

PubMed Central

Katzberg, Michael; Skorupa-Parachin, Nàdia; Gorwa-Grauslund, Marie-Françoise; Bertau, Martin

2010-01-01

The synthesis of pharmaceuticals and catalysts more and more relies on enantiopure chiral building blocks. These can be produced in an environmentally benign and efficient way via bioreduction of prochiral ketones catalyzed by dehydrogenases. A productive source of these biocatalysts is the yeast Saccharomyces cerevisiae, whose genome also encodes a reductase catalyzing the sequential reduction of the γ-diketone 2,5-hexanedione furnishing the diol (2S,5S)-hexanediol and the γ-hydroxyketone (5S)-hydroxy-2-hexanone in high enantio- as well as diastereoselectivity (ee and de >99.5%). This enzyme prefers NADPH as the hydrogen donating cofactor. As NADH is more stable and cheaper than NADPH it would be more effective if NADH could be used in cell-free bioreduction systems. To achieve this, the cofactor binding site of the dehydrogenase was altered by site-directed mutagenesis. The results show that the rational approach based on a homology model of the enzyme allowed us to generate a mutant enzyme having a relaxed cofactor preference and thus is able to use both NADPH and NADH. Results obtained from other mutants are discussed and point towards the limits of rationally designed mutants. PMID:20480039

7-endo selenocyclization reactions on chiral 3-prenyl and 3-cinnamyl-2-hydroxymethylperhydro-1,3-benzoxazine derivatives. A way to enantiopure 1,4-oxazepanes.

PubMed

Nieto, Javier; Andrés, Celia; Pérez-Encabo, Alfonso

2015-09-14

Enantiopure 1,4-oxazepane derivatives have been prepared by selenocyclofunctionalization of chiral 3-prenyl- and 3-cinnamyl-2-hydroxymethyl-substituted perhydro-1,3-benzoxazine derivatives. The 7-endo-cyclization occurs in high yields and diastereoselection. The regio- and stereochemistry of the cyclization products was dependent on the substitution pattern of the double bond, the nature of the hydroxyl group and the experimental conditions.

Diastereoselective reactions in glycine templates containing an ent-ardeemin fragment.

PubMed

Martín-Santamaría, Sonsoles; Corzo-Suárez, Raúl; Avendaño, Carmen; Espada, Modesta; Gago, Federico; García-Granda, Santiago; Rzepa, Henry S

2002-04-05

Self-consistent reaction field solvation models derived from SCF-MO calculations are shown to be reliable in modeling the diastereoselectivity of the reactions of the anion and cation derived from (4S)-2,4-dimethyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-dione (1) at C(1) with electrophiles and nucleophiles, respectively. The found anti/syn ratio of compound 8, which is a seco-ent-ardeemin analogue obtained by alkylation of 1 with gramine methiodide, confirms this computational model. A close similarity between the calculated geometry of the piperazine ring in the anti isomers of 1,2,4-trialkyl derivatives and that deduced from their (1)H NMR (solution) and X-ray data has been also established.

Lanthanum tricyanide-catalyzed acyl silane-ketone benzoin additions and kinetic resolution of resultant alpha-silyloxyketones.

PubMed

Tarr, James C; Johnson, Jeffrey S

2010-05-21

We report the full account of our efforts on the lanthanum tricyanide-catalyzed acyl silane-ketone benzoin reaction. The reaction exhibits a wide scope in both acyl silane (aryl, alkyl) and ketone (aryl-alkyl, alkyl-alkyl, aryl-aryl, alkenyl-alkyl, alkynyl-alkyl) coupling partners. The diastereoselectivity of the reaction has been examined in both cyclic and acyclic systems. Cyclohexanones give products arising from equatorial attack by the acyl silane. The diastereoselectivity of acyl silane addition to acyclic alpha-hydroxy ketones can be controlled by varying the protecting group to obtain either Felkin-Ahn or chelation control. The resultant alpha-silyloxyketone products can be resolved with selectivity factors from 10 to 15 by subjecting racemic ketone benzoin products to CBS reduction.

Conformationally constrained dipeptide surrogates with aromatic side-chains: synthesis of 4-aryl indolizidin-9-one amino acids by conjugate addition to a common alpha,omega-diaminoazelate enone intermediate.

PubMed

Cluzeau, Jérôme; Lubell, William D

2004-03-05

Four methyl 9-oxo-8-(N-(Boc)-amino)-4-phenyl-1-azabicyclo[4.3.0]nonane carboxylates (11, 4-Ph-I(9)aa-OMe) were synthesized from (2S,8S,5E)-di-tert-butyl-4-oxo-5-ene-2,8-bis[N-(PhF)amino]azelate [(5E)-7, PhF = 9-(9-phenylfluorenyl)] via a seven-step process featuring a conjugate addition/reductive amination/lactam cyclization sequence. Various nucleophiles were used in the conjugate addition reactions on enone (5E)-7 as a general route for making alpha,omega-diaminoazelates possessing different substituents in good yield albeit low diastereoselectivity except in the case of aryl Grignard reagents (9/1 to 15/1 drs). 6-Phenylazelates (6S)-8d and (6R)-8d were separated by chromatography and diastereoselective precipitation and independently transformed into 4-Ph-I(9)aa-OMe. From (6S)-8d, (2S,4R,6R,8S)-4-Ph-I(9)aa-OMe 11 was prepared selectively in 51% yield. Reductive amination of (6R)-8d provided the desired pipecolates 9 along with desamino compound 10, which was minimized by performing the hydrogenation in the presence of ammonium acetate. Subsequent ester exchange, lactam cyclization, and amine protection provided three products (2R,4S,6S,8R)-, (2R,4S,6S,8S)-, and (2S,4S,6R,8S)-4-Ph-I(9)aa-OMe 11 in 10, 6, and 6% yields, respectively, from (6R)-8d. Ester hydrolysis of (2S,4R,6R,8S)-11 furnished 4-phenyl indolizidin-9-one N-(Boc)amino acid 3 as a novel constrained Ala-Phe dipeptide surrogate for studying conformation-activity relationships of biologically active peptides.

Stereoselective rhodium-catalysed [2+2+2] cycloaddition of linear allene-ene/yne-allene substrates: reactivity and theoretical mechanistic studies.

PubMed

Haraburda, Ewelina; Torres, Óscar; Parella, Teodor; Solà, Miquel; Pla-Quintana, Anna

2014-04-22

Allene-ene-allene (2 and 5) and allene-yne-allene (3 and 7) N-tosyl and O-linked substrates were satisfactorily synthesised. The [2+2+2] cycloaddition reaction catalysed by the Wilkinson catalyst [RhCl(PPh3 )3 ] was evaluated. Substrates 2 and 5, which bear a double bond in the central position, gave a tricyclic structure in a reaction in which four contiguous stereogenic centres were formed as a single diastereomer. The reaction of substrates 3 and 7, which bear a triple bond in the central position, gave a tricyclic structure with a cyclohexenic ring core, again in a diastereoselective manner. All cycloadducts were formed by a regioselective reaction of the inner allene double bond and, therefore, feature an exocyclic diene motif. A Diels-Alder reaction on N-tosyl linked cycloadducts 8 and 10 allowed pentacyclic scaffolds to be diastereoselectively constructed. The reactivity of the allenes on [2+2+2] cycloaddition reactions was studied for the first time by density functional theory calculations. This mechanistic study rationalizes the order in which the unsaturations take part in the catalytic cycle, the reactivity of the two double bonds of the allene towards the [2+2+2] cycloaddition reaction, and the diastereoselectivity of the reaction. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mimics of pramanicin derived from pyroglutamic acid and their antibacterial activity.

PubMed

Tan, Song Wei Benjamin; Chai, Christina L L; Moloney, Mark G

2017-02-22

Mono and dihydroxypyrrolidinones are readily available by direct oxygenation of a pyroglutamate-derived bicyclic lactam with high diastereoselectivity, and these may be manipulated further in protected or unprotected form by Grignard addition to a pendant Weinreb amide to give acylhydroxypyrrolidinones, which are analogues of the natural product, pramanicin. Preliminary bioassay against S. aureus and E. coli indicated that some compounds exhibit selective Gram-negative antibacterial activity, and may offer promise for the development of novel systems suitable for antibacterial drug development.

Asymmetric Iridium Catalyzed C-C Coupling of Chiral Diols via Site-Selective Redox-Triggered Carbonyl Addition

PubMed Central

Shin, Inji; Krische, Michael J.

2015-01-01

Cyclometalated π-allyliridium C,O-benzoate complexes modified by axially chiral chelating phosphine ligands display a pronounced kinetic preference for primary alcohol dehydrogenation, enabling highly site-selective redox-triggered carbonyl additions of chiral primary-secondary 1,3-diols with exceptional levels of catalyst-directed diastereoselectivity. Unlike conventional methods for carbonyl allylation, the present redox-triggered alcohol C-H functionalizations bypass the use of protecting groups, premetalated reagents, and discrete alcohol-to-aldehyde redox reactions. PMID:26187028

Lanthanum Tricyanide-Catalyzed Acyl Silane-Ketone Benzoin Additions and Kinetic Resolution of Resultant α-Silyloxyketones

PubMed Central

Tarr, James C.

2010-01-01

We report the full account of our efforts on the lanthanum tricyanide-catalyzed acyl silane-ketone benzoin reaction. The reaction exhibits a wide scope in both acyl silane (aryl, alkyl) and ketone (aryl-alkyl, alkyl-alkyl, aryl-aryl, alkenyl-alkyl, alkynyl-alkyl) coupling partners. The diastereoselectivity of the reaction has been examined in both cyclic and acyclic systems. Cyclohexanones give products arising from equatorial attack by the acyl silane. The diastereoselectivity of acyl silane addition to acyclic α-hydroxy ketones can be controlled by varying the protecting group to obtain either Felkin-Ahn or chelation control. The resultant α-silyloxyketone products can be resolved with selectivity factors from 10 to 15 by subjecting racemic ketone benzoin products to CBS reduction. PMID:20392127

Rhodium-catalyzed [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes and CO: reaction design, development, application in natural product synthesis, and inspiration for developing new reactions for synthesis of eight-membered carbocycles.

PubMed

Wang, Yi; Yu, Zhi-Xiang

2015-08-18

Practical syntheses of natural products and their analogues with eight-membered carbocyclic skeletons are important for medicinal and biological investigations. However, methods and strategies to construct the eight-membered carbocycles are limited. Therefore, developing new methods to synthesize the eight-membered carbocycles is highly desired. In this Account, we describe our development of three rhodium-catalyzed cycloadditions for the construction of the eight-membered carbocycles, which have great potential in addressing the challenges in the synthesis of medium-sized ring systems. The first reaction described in this Account is our computationally designed rhodium-catalyzed two-component [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes (ene-VCPs) and CO for the diastereoselective construction of bi- and tricyclic cyclooctenones. The design of this reaction is based on the hypothesis that the C(sp(3))-C(sp(3)) reductive elimination of the eight-membered rhodacycle intermediate generated from the rhodium-catalyzed cyclopropane cleavage and alkene insertion, giving Wender's [5 + 2] cycloadduct, is not easy. Under CO atmosphere, CO insertion may occur rapidly, converting the eight-membered rhodacycle into a nine-membered rhodacycle, which then undergoes an easy C(sp(2))-C(sp(3)) reductive elimination process and furnishes the [5 + 2 + 1] product. This hypothesis was supported by our preliminary DFT studies and also served as inspiration for the development of two [7 + 1] cycloadditions: the [7 + 1] cycloaddition of buta-1,3-dienylcyclopropanes (BDCPs) and CO for the construction of cyclooctadienones, and the benzo/[7 + 1] cycloaddition of cyclopropyl-benzocyclobutenes (CP-BCBs) and CO to synthesize the benzocyclooctenones. The efficiency of these rhodium-catalyzed cycloadditions can be revealed by the application in natural product synthesis. Two eight-membered ring-containing natural products, (±)-asterisca-3(15),6-diene and (+)-asteriscanolide, have been synthesized using the [5 + 2 + 1] cycloaddition as the key step. In the latter case, excellent asymmetric induction was obtained using a chiral substrate. The efficiency of the [5 + 2 + 1] reaction was further demonstrated by the synthesis of four sesquiterpene natural products, (±)-pentalenene, (+)-hirsutene, (±)-1-desoxyhypnophilin, and (±)-hirsutic acid C, containing linear or branched triquinane skeletons utilizing the tandem or stepwise [5 + 2 + 1] cycloaddition/aldol reaction strategy. With the success of [5 + 2 + 1] cycloaddition in natural product synthesis, application of the [7 + 1] and benzo/[7 + 1] cycloadditions in target- and function-oriented syntheses can be envisioned.

Diastereoselective carbocyclization of 1,6-heptadienes triggered by rhodium-catalyzed activation of an olefinic C-H bond.

PubMed

Aïssa, Christophe; Ho, Kelvin Y T; Tetlow, Daniel J; Pin-Nó, María

2014-04-14

The use of α,ω-dienes as functionalization reagents for olefinic carbon-hydrogen bonds has been rarely studied. Reported herein is the rhodium(I)-catalyzed rearrangement of prochiral 1,6-heptadienes into [2,2,1]-cycloheptane derivatives with concomitant creation of at least three stereogenic centers and complete diastereocontrol. Deuterium-labeling studies and the isolation of a key intermediate are consistent with a group-directed C-H bond activation, followed by two consecutive migratory insertions, with only the latter step being diastereoselective. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Effect of additives on chemoselectivity and diastereoselectivity in the catalytic epoxidation of chiral allylic alcohols with hydrogen peroxide and binuclear manganese complexes.

PubMed

Kilic, Hamdullah; Adam, Waldemar; Alsters, Paul L

2009-02-06

The catalytic oxidations of chiral allylic alcohols 2 by manganese complexes of the cyclic triamine 1,4,7-trimethyl-1,4,7-triazacyclononane (tmtacn) 1 and hydrogen peroxide as oxygen donor in the presence of co-catalyst are investigated to understand the factors that affect the catalyst selectivity. Chemoselectivity and diastereoselectivity of catalyst 1 are significantly affected by the structure of the allylic alcohol and the nature and amount of co-catalyst. More pronounced is the influence of the amount of added molar equivalents of H(2)O(2) (20-110 mol % with respect to the substrate). Our present results reflect the complex redox chemistry of the Mn catalyst 1/H(2)O(2)/co-catalyst system in the early phase of the alkene oxidation.

Palladium(II)-Catalyzed Annulation between ortho-Alkenylphenols and Allenes. Key Role of the Metal Geometry in Determining the Reaction Outcome.

PubMed

Casanova, Noelia; Del Rio, Karina P; García-Fandiño, Rebeca; Mascareñas, José L; Gulías, Moisés

2016-05-06

2-Alkenylphenols react with allenes, upon treatment with catalytic amounts of Pd(II) and Cu(II), to give benzoxepine products in high yields and with very good regio- and diastereoselectivities. This contrasts with the results obtained with Rh catalysts, which provided chromene-like products through a pathway involving a β-hydrogen elimination step. Computational studies suggest that the square planar geometry of the palladium is critical to favor the reductive elimination process required for the formation of the oxepine products.

Lewis base catalyzed aldol additions of chiral trichlorosilyl enolates and silyl enol ethers.

PubMed

Denmark, Scott E; Fujimori, Shinji; Pham, Son M

2005-12-23

[structures: see text] The consequences of double diastereodifferentiation in chiral Lewis base catalyzed aldol additions using chiral enoxysilanes derived from lactate, 3-hydroxyisobutyrate, and 3-hydroxybutyrate have been investigated. Trichlorosilyl enolates derived from the chiral methyl and ethyl ketones were subjected to aldolization in the presence of phosphoramides, and the intrinsic selectivity of these enolates and the external stereoinduction from chiral catalyst were studied. In the reactions with the lactate derived enolate, the strong internal stereoinduction dominated the stereochemical outcome of the aldol addition. For the 3-hydroxyisobutyrate- and 3-hydroxybutyrate derived enolates, the catalyst-controlled diastereoselectivities were observed, and the resident stereogenic centers exerted marginal influence. The corresponding trimethylsilyl enol ethers were employed in SiCl4/bisphosphoramide catalyzed aldol additions, and the effect of double diastereodifferentiation was also investigated. The overall diastereoselection of the process was again controlled by the strong external influence of the catalyst.

Felkin-Anh stereoselectivity in cycloadditions of acetylketene: evidence for a concerted, pseudopericyclic pathway

PubMed

Shumway; Ham; Moer; Whittlesey; Birney

2000-11-17

The cycloadditions of acetylketene with alpha-chiral aldehydes and ketones are shown to be diastereoselective, forming a tertiary or quaternary chiral center at an acetal or ketal carbon with good stereocontrol. X-ray crystallography of a minor product (5b) shows that the major products (e.g., 4b) are those predicted by the Felkin-Anh model. Transition states are reported at the MP2/6-31G level for the addition of ethanal to formylketene and at the B3LYP/6-31G level for the addition of 2-phenylpropanal. The ground-state conformations of the reactants and products are used to rationalize the relative energies and geometries of the transition states without the need to invoke the Cieplak hypothesis. However, chiral substituents on the alpha-oxoketene show no diastereoselectivity. These experimental and computational results are only consistent with the nearly planar, pseudopericyclic transition state previously proposed.

Rigid Dipeptide Mimics: Synthesis of Enantiopure 5- and 7-Benzyl and 5,7-Dibenzyl Indolizidinone Amino Acids via Enolization and Alkylation of delta-Oxo alpha,omega-Di-[N-(9-(9-phenylfluorenyl))amino]azelate Esters.

PubMed

Polyak, Felix; Lubell, William D.

1998-08-21

Azabicyclo[X.Y.0]alkane amino acids are tools for constructing mimics of peptide structure and templates for generating combinatorial libraries for drug discovery. Our methodology for synthesizing these conformationally rigid dipeptides has been elaborated such that alkyl groups can be appended onto the heterocycle to generate mimics of peptide backbone and side-chain structure. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/ketone alkylation/reductive amination/lactam cyclization sequence that furnished alkyl-branched azabicyclo[4.3.0]alkane amino acid. Enantiopure 5-benzyl-, 7-benzyl-, and 5,7-dibenzylindolizidinone amino acids 2-4 were stereoselectively synthesized via efficient reaction sequences featuring the alkylation of di-tert-butyl alpha,omega-di-[N-(PhF)amino]azelate delta-ketone 5. A variety of alkyl halides were readily added to the enolate of ketone 5 to provide mono- and dialkylated ketones 6 and 7. Hydride additions to 6 and 7, methanesulfonations, and intramolecular S(N)2 displacements by the PhF amine gave 5-alkylprolines that were converted by lactam cyclizations into 7- and 5-benzyl-, as well as 5,7-dibenzyl-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylate methyl esters 10, 11, and 14. Epimerization of the alkyl-branched stereocenter via an iminium-enaminium equilibrium proved effective for controlling diastereoselectivity in reductive aminations with 6 and 7 in order to furnish 5-alkylprolines that were similarly converted to 7- benzyl- and 5,7-dibenzylindolizidinone N-(BOC)amino esters 10 and 14. Ester hydrolysis with hydroxide ion and potassium trimethylsilanolate then gave enantiopure indolizidinone amino acids 2-4. Epimerization at C-9 of benzylindolizidinone amino esters was also used to provide alternative diastereomers of 10, 11, and 14. This practical methodology for introducing side-chain groups onto the heterocycle with regioselective and diastereoselective control is designed to enhance the use of alkyl-branched azabicycloalkane amino acids for the exploration of conformation-activity relationships of various biologically active peptides.

Tandem catalytic allylic amination and [2,3]-Stevens rearrangement of tertiary amines.

PubMed

Soheili, Arash; Tambar, Uttam K

2011-08-24

We have developed a catalytic allylic amination involving tertiary aminoesters and allylcarbonates, which is the first example of the use of tertiary amines as intermolecular nucleophiles in metal-catalyzed allylic substitution chemistry. This process is employed in a tandem ammonium ylide generation/[2,3]-rearrangement reaction, which formally represents a palladium-catalyzed Stevens rearrangement. Low catalyst loadings and mild reaction conditions are compatible with an unprecedented substrate scope for the ammonium ylide functionality, and products are generated in high yields and diastereoselectivities. Mechanistic studies suggested the reversible formation of an ammonium intermediate.

β-Amino acid catalyzed asymmetric Michael additions: design of organocatalysts with catalytic acid/base dyad inspired by serine proteases.

PubMed

Yang, Hui; Wong, Ming Wah

2011-09-16

A new type of chiral β-amino acid catalyst has been computationally designed, mimicking the enzyme catalysis of serine proteases. Our catalyst approach is based on the bioinspired catalytic acid/base dyad, namely, a carboxyl and imidazole pair. DFT calculations predict that this designed organocatalyst catalyzes Michael additions of aldehydes to nitroalkenes with excellent enantioselectivities and remarkably high anti diastereoselectivities. The unusual stacked geometry of the enamine intermediate, hydrogen bonding network, and the adoption of an exo transition state are the keys to understand the stereoselectivity. © 2011 American Chemical Society

Carbon-fluorine bond activation coupled with carbon-hydrogen bond formation alpha to iridium: kinetics, mechanism, and diastereoselectivity.

PubMed

Garratt, Shaun A; Hughes, Russell P; Kovacik, Ivan; Ward, Antony J; Willemsen, Stefan; Zhang, Donghui

2005-11-09

Reactions of iridium(fluoroalkyl)hydride complexes CpIr(PMe(3))(CF(2)R(F))Y (R(F) = F, CF(3); Y = H, D) with LutHX (Lut = 2,6-dimethylpyridine; X = Cl, I) results in C-F activation coupled with hydride migration to give CpIr(PMe(3))(CYFR(F))X as variable mixtures of diastereomers. Solution conformations and relative diastereomer configurations of the products have been determined by (19)F{(1)H}HOESY NMR to be (S(C), S(Ir))(R(C), R(Ir)) for the kinetic diastereomer and (R(C), S(Ir))(S(C), R(Ir)) for its thermodynamic counterpart. Isotope labeling experiments using LutDCl/CpIr(PMe(3))(CF(2)R(F))H and CpIr(PMe(3))(CF(2)R(F))D/LutHCl) showed that, unlike a previously studied system, H/D exchange is faster than protonation of the alpha-CF bond, giving an identical mixture of product isotopologues from both reaction mixtures. The kinetic rate law shows a first-order dependence on the concentration of iridium substrate, but a half-order dependence on that of LutHCl; this is interpreted to mean that LutHCl dissociates to give HCl as the active protic source for C-F bond activation. Detailed kinetic studies are reported, which demonstrate that lack of complete diastereoselectivity is not a function of the C-F bond activation/H migration steps but that a cationic intermediate plays a double role in loss of diastereoselectivity; the intermediate can undergo epimerization at iridium before being trapped by halide and can also catalyze the epimerization of kinetic diastereomer product to thermodynamic product. A detailed mechanism is proposed and simulations performed to fit the kinetic data.

Chiral aldehydes in hydrocarbons: diastereoselective nucleophilic addition, NMR, and CD spectroscopy reveal dynamic solvation effects.

PubMed

Cainelli, Gianfranco; Galletti, Paola; Pieraccini, Silvia; Quintavalla, Arianna; Giacomini, Daria; Piero Spada, Gian

2004-01-01

Temperature-dependent studies on the diastereoselective nucleophilic addition of n- BuLi to alpha-chiral aldehydes as (S)-O-(t-butyl-dimethylsilyl)lactal, (S)-O-(t-butyl-dimethylsilyl) mandelic aldehyde, and (R)-2-phenylpropanal in n-decane and n-dodecane reveal dynamic solvation phenomena with the presence of inversion temperatures (T(inv)) in the Eyring plots of ln (anti/syn) vs. 1/ T. These dynamic solvent effects were disclosed by temperature-dependent studies of the (13)C NMR, CD, and UV spectra of the starting aldehydes in solution of n-decane and n-dodecane. The concomitant presence of three peculiar temperatures T(CD), T(UV), and T(NMR), whose values are identical and match T(inv), clearly confirms our earlier interpretation of the solvent-dependent nature of T(inv). The inversion temperature, as well as T(CD), T(UV), and T(NMR) represents the interconversion temperature of two different solvation clusters which act as two different supramolecules with different stereoselectivities. Copyright 2003 Wiley-Liss, Inc.

Asymmetric Desymmetrization of 1,3-Diketones via Intramolecular Benzoin Reaction.

PubMed

Li, Yuanzhen; Yang, Shuang; Wen, Genfa; Lin, Qiqiao; Zhang, Guoxiang; Qiu, Lin; Zhang, Xiaoyan; Du, Guangfen; Fang, Xinqiang

2016-04-01

A general method for the asymmetric desymmetrization of 1,3-diketone substrates via chiral N-heterocyclic carbene catalyzed intramolecular benzoin reactions was developed. Five- and six-membered cyclic ketones bearing two contiguous fully substituted stereocenters were generated with excellent diastereoselectivities and moderate to excellent enantioselectivities.

Hydrogenation of fluoroarenes: Direct access to all-cis-(multi)fluorinated cycloalkanes.

PubMed

Wiesenfeldt, Mario P; Nairoukh, Zackaria; Li, Wei; Glorius, Frank

2017-09-01

All-c is -multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular, they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Very few such motifs have been prepared, as their syntheses require multistep sequences from diastereoselectively prefunctionalized precursors. Herein we report a synthetic strategy to access these valuable materials via the rhodium-cyclic (alkyl)(amino)carbene (CAAC)-catalyzed hydrogenation of readily available fluorinated arenes in hexane. This route enables the scalable single-step preparation of an abundance of multisubstituted and multifluorinated cycloalkanes, including all- cis -1,2,3,4,5,6-hexafluorocyclohexane as well as cis-configured fluorinated aliphatic heterocycles. Copyright © 2017, American Association for the Advancement of Science.

Enantioselective Intermolecular [2 + 2] Photocycloaddition Reactions of 2(1H)-Quinolones Induced by Visible Light Irradiation

PubMed Central

2016-01-01

In the presence of a chiral thioxanthone catalyst (10 mol %) the title compounds underwent a clean intermolecular [2 + 2] photocycloaddition with electron-deficient olefins at λ = 419 nm. The reactions not only proceeded with excellent regio- and diastereoselectivity but also delivered the respective cyclobutane products with significant enantiomeric excess (up to 95% ee). Key to the success of the reactions is a two-point hydrogen bonding between quinolone and catalyst enabling efficient energy transfer and high enantioface differentiation. Preliminary work indicated that solar irradiation can be used for this process and that the substrate scope can be further expanded to isoquinolones. PMID:27268908

Another side of the oxazaphospholidine oxide chiral ortho-directing group.

PubMed

Martins, Nelson; Mateus, Nuno; Vinci, Daniele; Saidi, Ourida; Brigas, Amadeu; Bacsa, John; Xiao, Jianliang

2012-05-28

A new ferrocenyl oxazaphospholidine oxide 3 was synthesized together with its P-epimer 2 in the reaction of ferrocene lithium with phosphoramidite chloride 1. 3 was successfully derivatized into planar chiral 1,2-ferrocenes, including phosphine ligands, via highly diastereoselective ortho-lithiation and subsequent functionalization; these compounds display opposite planar chirality to those obtained from 2. Some of these 1,2-ferrocenes were further lithiated, allowing for the introduction of a free phosphine group at the oxazaphospholidine ring. The X-ray structures of the compounds 2 and 3 as well as those of the new 1,2-ferrocenes 4 and 7 have been determined.

Asymmetric radical alkylation of N-sulfinimines under visible light photocatalytic conditions.

PubMed

Garrido-Castro, Alberto F; Choubane, Houcine; Daaou, Mortada; Maestro, M Carmen; Alemán, José

2017-07-06

In this communication, a new photocatalytic strategy for the addition of alkyl-radical derivatives to N-sulfinimines with complete diastereoselectivity and moderate to good yields is presented. This is the first asymmetric photocatalytic addition to N-sulfinimines under visible light irradiation with smooth conditions and functional group tolerance.

Synthesis of triple-stranded complexes using bis(dipyrromethene) ligands.

PubMed

Zhang, Zhan; Dolphin, David

2010-12-20

The reaction of an α-free, β,β'-linked bis(dipyrromethene) ligand with Fe(3+) or Co(3+) led to noninterconvertible triple-stranded helicates and mesocates. In the present context, a stable α-free ligand 2 has been developed and complexation of ligands 1 and 2 with diamagnetic Co(3+), Ga(3+), and In(3+) has been studied. The triple-stranded M(2)1(3) (M = Ga, In) and M(2)2(3) (M = Co, Ga, In) complexes were characterized using matrix-assisted laser desorption ionization time-of-flight spectrometry, (1)H NMR and UV-vis spectroscopy, and X-ray crystallography. Again, the (1)H NMR analysis showed that both the triple-stranded helicates and mesocates were generated in this metal-directed assembly. Consistent with our previous finding on coordinatively inert Co(3+) complexes, variable-temperature NMR spectroscopy indicated that the triple-stranded helicate and mesocate of labile In(3+) did not interconvert in solution, either. However, the diastereoselectivity of the M(2)2(3) complexes was found to improve with an increase in the reaction temperature. Taken together, this study complements the coordination chemistry of poly(dipyrromethene) ligands and provides further insight into the formation of helicates versus mesocates.

The Darzens Condensation: Structure Determination through Spectral Analysis and Understanding Substrate Reactivity

ERIC Educational Resources Information Center

Crouch, R. David; Holden, Michael S.; Romany, Candice A.

2004-01-01

The use of KOH and a phase transfer catalyst to achieve diastereoselective Darzens condensation is described and a modification of the method for use in organic chemistry is carried out. The experiment involves the condensation of t-butyl chloroacentate and p-tolualdehyde with KOH and benzyltriethylammonium chloride in THF.

A synthetic approach to the fusicoccane A-B ring fragment based on a Pauson-Khand cycloaddition/Norrish type 1 fragmentation.

PubMed

Dake, Gregory R; Fenster, Erik E; Patrick, Brian O

2008-09-05

A synthetic approach to the A-B ring system within the fusicoccane family of diterpenes is presented. Key steps in this approach are a diastereoselective Pauson-Khand reaction, a Norrish 1 photofragmentation, a Charette cyclopropanation, and a ring-closing metathesis process.

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C-H Activation Reactions: An Experimental and Computational Study.

PubMed

Piou, Tiffany; Romanov-Michailidis, Fedor; Romanova-Michaelides, Maria; Jackson, Kelvin E; Semakul, Natthawat; Taggart, Trevor D; Newell, Brian S; Rithner, Christopher D; Paton, Robert S; Rovis, Tomislav

2017-01-25

Cp X Rh(III)-catalyzed C-H functionalization reactions are a proven method for the efficient assembly of small molecules. However, rationalization of the effects of cyclopentadienyl (Cp X ) ligand structure on reaction rate and selectivity has been viewed as a black box, and a truly systematic study is lacking. Consequently, predicting the outcomes of these reactions is challenging because subtle variations in ligand structure can cause notable changes in reaction behavior. A predictive tool is, nonetheless, of considerable value to the community as it would greatly accelerate reaction development. Designing a data set in which the steric and electronic properties of the Cp X Rh(III) catalysts were systematically varied allowed us to apply multivariate linear regression algorithms to establish correlations between these catalyst-based descriptors and the regio-, diastereoselectivity, and rate of model reactions. This, in turn, led to the development of quantitative predictive models that describe catalyst performance. Our newly described cone angles and Sterimol parameters for Cp X ligands served as highly correlative steric descriptors in the regression models. Through rational design of training and validation sets, key diastereoselectivity outliers were identified. Computations reveal the origins of the outstanding stereoinduction displayed by these outliers. The results are consistent with partial η 5 -η 3 ligand slippage that occurs in the transition state of the selectivity-determining step. In addition to the instructive value of our study, we believe that the insights gained are transposable to other group 9 transition metals and pave the way toward rational design of C-H functionalization catalysts.

Three-Component Reaction Discovery Enabled by Mass Spectrometry of Self-Assembled Monolayers

PubMed Central

Montavon, Timothy J.; Li, Jing; Cabrera-Pardo, Jaime R.; Mrksich, Milan; Kozmin, Sergey A.

2011-01-01

Multi-component reactions have been extensively employed in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform, which can be used for identification of new multi-component transformations. Our approach is based on the parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyze a previously unknown condensation of siloxy alkynes, aldehydes and amines to produce 3-hydroxy amides with high efficiency and diastereoselectivity. The reaction was further optimized using solution phase methods. PMID:22169871

Rhodium(i)-catalyzed asymmetric [4 + 2] cycloaddition reactions of 2-alkylenecyclobutanols with cyclic enones through C–C bond cleavage: efficient access to trans-bicyclic compounds† †Electronic supplementary information (ESI) available. CCDC 1575240. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04784c

PubMed Central

Zheng, Xinxin; Guo, Rui

2018-01-01

We report a rhodium-catalyzed asymmetric formal intermolecular [4 + 2] cycloaddition reaction of 2-alkylenecyclobutanols with α,β-unsaturated cyclic ketones leading to synthetically useful trans-bicyclic molecules. Three consecutive stereogenic centers are formed in a highly enantio- and diastereoselective manner. Stepwise C–C bond cleavage and annulation are likely involved in the reaction pathway. Here, iPr-Duphos is the viable chiral ligand that promotes excellent enantio-control. PMID:29675233

Catalytic Enantioselective and Diastereoselective Allylic Alkylation with Fluoroenolates: Efficient Access to C3-Fluorinated and All-Carbon Quaternary Oxindoles

PubMed Central

Balaraman, Kaluvu; Wolf, Christian

2017-01-01

Synthetically versatile 3,3-disubstituted fluorooxindoles exhibiting vicinal chirality centers were obtained in high yields and with excellent enantio-, diastereo- and regioselectivity by catalytic asymmetric fluoroenolate alkylation with allylic acetates. The reaction proceeds under mild conditions and can be upscaled without compromising the asymmetric induction. The unique synthetic usefulness of the products is highlighted with the incorporation of additional functionalities and the formation of 3-fluorinated oxindoles exhibiting an array of four adjacent chirality centers. A new C-F bond functionalization path that provides unprecedented means for stereoselective generation of a chiral quaternary carbon center in the alkaloid scaffold is introduced. PMID:28026079

Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Key, Hanna M.; Dydio, Paweł; Liu, Zhennan

Enzymes catalyze organic transformations with exquisite levels of selectivity, including chemoselectivity, stereoselectivity, and substrate selectivity, but the types of reactions catalyzed by enzymes are more limited than those of chemical catalysts. Thus, the convergence of chemical catalysis and biocatalysis can enable enzymatic systems to catalyze abiological reactions with high selectivity. Recently, we disclosed artificial enzymes constructed from the apo form of heme proteins and iridium porphyrins that catalyze the insertion of carbenes into a C-H bond. Here, we postulated that the same type of Ir(Me)-PIX enzymes could catalyze the cyclopropanation of a broad range of alkenes with control of multiplemore » modes of selectivity. Here, we report the evolution of artificial enzymes that are highly active and highly stereoselective for the addition of carbenes to a wide range of alkenes. These enzymes catalyze the cyclopropanation of terminal and internal, activated and unactivated, electron-rich and electron-deficient, conjugated and nonconjugated alkenes. In particular, Ir(Me)-PIX enzymes derived from CYP119 catalyze highly enantio- and diastereoselective cyclopropanations of styrene with ±98% ee, > 70:1 dr, > 75% yield, and ~10,000 turnovers (TON), as well as 1,2-disubstituted styrenes with up to 99% ee, 35:1 dr, and 54% yield. Moreover, Ir(Me)-PIX enzymes catalyze cyclopropanation of internal, unactivated alkenes with up to 99% stereoselectivity, 76% yield, and 1300 TON. They also catalyze cyclopropanation of natural products with diastereoselectivities that are complementary to those attained with standard transition metal catalysts. Finally, Ir(Me)-PIX P450 variants react with substrate selectivity that is reminiscent of natural enzymes; they react preferentially with less reactive internal alkenes in the presence of more reactive terminal alkenes. Altogether, the studies reveal the suitability of Ir-containing P450s to combine the broad reactivity and substrate scope of transition metal catalysts with the exquisite selectivity of enzymes, generating catalysts that enable reactions to occur with levels and modes of activity and selectivity previously unattainable with natural enzymes or transition metal complexes alone.« less

Beyond Iron: Iridium-Containing P450 Enzymes for Selective Cyclopropanations of Structurally Diverse Alkenes

DOE PAGES

Key, Hanna M.; Dydio, Paweł; Liu, Zhennan; ...

2017-04-01

Enzymes catalyze organic transformations with exquisite levels of selectivity, including chemoselectivity, stereoselectivity, and substrate selectivity, but the types of reactions catalyzed by enzymes are more limited than those of chemical catalysts. Thus, the convergence of chemical catalysis and biocatalysis can enable enzymatic systems to catalyze abiological reactions with high selectivity. Recently, we disclosed artificial enzymes constructed from the apo form of heme proteins and iridium porphyrins that catalyze the insertion of carbenes into a C-H bond. Here, we postulated that the same type of Ir(Me)-PIX enzymes could catalyze the cyclopropanation of a broad range of alkenes with control of multiplemore » modes of selectivity. Here, we report the evolution of artificial enzymes that are highly active and highly stereoselective for the addition of carbenes to a wide range of alkenes. These enzymes catalyze the cyclopropanation of terminal and internal, activated and unactivated, electron-rich and electron-deficient, conjugated and nonconjugated alkenes. In particular, Ir(Me)-PIX enzymes derived from CYP119 catalyze highly enantio- and diastereoselective cyclopropanations of styrene with ±98% ee, > 70:1 dr, > 75% yield, and ~10,000 turnovers (TON), as well as 1,2-disubstituted styrenes with up to 99% ee, 35:1 dr, and 54% yield. Moreover, Ir(Me)-PIX enzymes catalyze cyclopropanation of internal, unactivated alkenes with up to 99% stereoselectivity, 76% yield, and 1300 TON. They also catalyze cyclopropanation of natural products with diastereoselectivities that are complementary to those attained with standard transition metal catalysts. Finally, Ir(Me)-PIX P450 variants react with substrate selectivity that is reminiscent of natural enzymes; they react preferentially with less reactive internal alkenes in the presence of more reactive terminal alkenes. Altogether, the studies reveal the suitability of Ir-containing P450s to combine the broad reactivity and substrate scope of transition metal catalysts with the exquisite selectivity of enzymes, generating catalysts that enable reactions to occur with levels and modes of activity and selectivity previously unattainable with natural enzymes or transition metal complexes alone.« less

Main-chain optically active riboflavin polymer for asymmetric catalysis and its vapochromic behavior.

PubMed

Iida, Hiroki; Iwahana, Soichiro; Mizoguchi, Tomohisa; Yashima, Eiji

2012-09-12

A novel optically active polymer consisting of riboflavin units as the main chain (poly-1) was prepared from naturally occurring riboflavin (vitamin B(2)) in three steps. The riboflavin residues of poly-1 were converted to 5-ethylriboflavinium cations (giving poly-2), which could be reversibly transformed into the corresponding 4a-hydroxyriboflavins (giving poly-2OH) through hydroxylation/dehydroxylation reactions. This reversible structural change was accompanied by a visible color change along with significant changes in the absorption and circular dichroism (CD) spectra. The nuclear Overhauser effect spectroscopy (NOESY) and CD spectra of poly-2 revealed a supramolecularly twisted helical structure with excess one-handedness through face-to-face stacking of the intermolecular riboflavinium units, as evidenced by the apparent NOE correlations between the interstrand riboflavin units and intense Cotton effects induced in the flavinium chromophore regions. The hydroxylation of poly-2 at the 4a-position proceeded in a diastereoselective fashion via chirality transfer from the induced supramolecular helical chirality assisted by the ribityl pendants, resulting in a 83:17 diastereomeric mixture of poly-2OH. The diastereoselectivity of poly-2 was remarkably higher than that of the corresponding monomeric model (64.5:35.5), indicating amplification of the chirality resulting from the supramolecular chirality induced in the stacked poly-2 backbones. The optically active poly-2 efficiently catalyzed the asymmetric organocatalytic oxidation of sulfides with hydrogen peroxide, yielding optically active sulfoxides with up to 60% enantiomeric excess (ee), whose enantioselectivity was higher than that catalyzed by the monomeric counterpart (30% ee). In addition, upon exposure to primary and secondary amines, poly-2 exhibited unique high-speed vapochromic behavior arising from the formation of 4a-amine adducts in the film.

Indium-mediated asymmetric barbier-type allylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents.

PubMed

Haddad, Terra D; Hirayama, Lacie C; Singaram, Bakthan

2010-02-05

We report a simple, efficient, and general method for the indium-mediated enantioselective allylation of aromatic and aliphatic aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 99%) and enantiomeric excess (up to 93%). Our method is able to tolerate various functional groups, such as esters, nitriles, and phenols. Additionally, more substituted allyl bromides, such as crotyl and cinnamyl bromide, can be used providing moderate enantioselectivity (72% and 56%, respectively) and excellent diastereoselectivity when employing cinnamyl bromide (>95/5 anti/syn). However, the distereoselectivity when using crotyl bromide was poor and other functionalized allyl bromides under our method afforded low enantioselectivities for the alcohol products. In these types of indium-mediated additions, solvent plays a major role in determining the nature of the organoindium intermediate and we observed the susceptibility of some allylindium intermediates to hydrolysis in protic solvents. Under our reaction conditions using a polar aprotic solvent, we suggest that an allylindium(III) species is the active allylating intermediate. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.

Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions.

PubMed

Denmark, Scott E; Heemstra, John R

2007-07-20

The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.

1,4-Hydroiodination of dienyl alcohols with TMSI to form homoallylic alcohols containing a multisubstituted Z-alkene and application to Prins cyclization.

PubMed

Xu, Yongjin; Yin, Zhiping; Lin, Xinglong; Gan, Zubao; He, Yanyang; Gao, Lu; Song, Zhenlei

2015-04-17

A regioselective 1,4-hydroiodination of dienyl alcohols has been developed using trimethylsilyl iodide as Lewis acid and iodide source. A range of homoallylic alcohols containing a multisubstituted Z-alkene was synthesized with good to excellent configurational control. The approach was applied in sequential hydroiodination/Prins cyclization to afford multisubstituted tetrahydropyrans diastereoselectively.

Thiazine-2-thiones as Masked 1-Azadienes in Cascade Dimerization Reactions).

PubMed

Kruithof, Art; Vande Velde, Christophe M L; Ruijter, Eelco; Orru, Romano V A

2017-03-28

We report the unexpected formation of a 1-azadiene dimer from 4,6-diphenyl-3,6-dihydro-2 H -1,3-thiazine-2-thiones under prolonged microwave irradiation. In this manner, thiazine-2-thiones act as "masked" 1-azadiene equivalents, which makes them useful synthetic tools to access complex heterocyclic frameworks. We compare this dimerization with earlier approaches and elaborate on the observed diastereoselectivity.

N719 dye-sensitized organophotocatalysis: enantioselective tandem Michael addition/oxyamination of aldehydes.

PubMed

Yoon, Hyo-Sang; Ho, Xuan-Huong; Jang, Jiyeon; Lee, Hwa-Jung; Kim, Seung-Joo; Jang, Hye-Young

2012-07-06

A remarkably efficient photosensitizer, N719 dye, was used in asymmetric tandem Michael addition/oxyamination of aldehydes, rendering α,β-substituted aldehydes in good yields with excellent levels of enantioselectivity and diastereoselectivity. This is the first report of a multiorganocatalytic reaction involving iminium catalysis and photoinduced singly occupied molecular orbital (SOMO) catalysis. This reaction is expected to expand the scope of tandem organocatalytic reactions.

Protease-catalysed Direct Asymmetric Mannich Reaction in Organic Solvent

NASA Astrophysics Data System (ADS)

Xue, Yang; Li, Ling-Po; He, Yan-Hong; Guan, Zhi

2012-10-01

We reported the first enzyme-catalysed, direct, three-component asymmetric Mannich reaction using protease type XIV from Streptomyces griseus (SGP) in acetonitrile. Yields of up to 92% with enantioselectivities of up to 88% e.e. and diastereoselectivities of up to 92:8 (syn:anti) were achieved under the optimised conditions. This enzyme's catalytic promiscuity expands the application of this biocatalyst and provides a potential alternative method for asymmetric Mannich reactions.

cis-Stilbene and (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)benzene as mechanistic probes in the Mn(III)(salen)-catalyzed epoxidation: influence of the oxygen source and the counterion on the diastereoselectivity of the competitive concerted and radical-type oxygen transfer.

PubMed

Adam, Waldemar; Roschmann, Konrad J; Saha-Möller, Chantu R; Seebach, Dieter

2002-05-08

cis-Stilbene (1) has been epoxidized by a set of diverse oxygen donors [OxD], catalyzed by the Mn(III)(salen)X complexes 3 (X = Cl, PF(6)), to afford a mixture of cis- and trans-epoxides 2. The cis/trans ratios range from 29:71 (extensive isomerization) to 92:8, which depends both on the oxygen source [OxD] and on the counterion X of the catalyst. When (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)-benzene (4) is used as substrate, a mechanistic probe which differentiates between radical and cationic intermediates, no cationic ring-opening products are found in this epoxidation reaction; thus, isomerized epoxide product arises from intermediary radicals. The dependence of the diastereoselectivity on the oxygen source is rationalized in terms of a bifurcation step in the catalytic cycle, in which concerted Lewis-acid-activated oxygen transfer competes with stepwise epoxidation by the established Mn(V)(oxo) species. The experimental counterion effect is attributed to the computationally assessed ligand-dependent reaction profiles and stereoselectivities of the singlet, triplet, and quintet spin states available to the manganese species.

Preparation of immobilized L-prolinamide via enzymatic polymerization of phenolic L-prolinamide and evaluation of its catalytic performance for direct asymmetric aldol reaction.

PubMed

Qu, Chengke; Zhao, Wenshan; Zhang, Lei; Cui, Yuanchen

2014-04-01

Phenolic L-prolinamide was allowed to participate in enzymatic polymerization with horseradish peroxidase as the catalyst, generating immobilized L-prolinamide. The catalytic performance of the resultant polymer-supported L-prolinamide for direct asymmetric aldol reaction between aromatic aldehyde and cyclohexanone was studied. The results show that as prepared L-prolinamide can catalyze the aldol reaction at room temperature in the presence of H2O. Relevant aldol addition products are obtained with good yields (up to 91%), high diastereoselectivities (up to 6:94 dr), and medium enantioselectivities (up to 87% ee). Moreover, the title polymer-supported catalyst can be recovered and reused for at least five cycles while the activity remains almost unchanged. Copyright © 2014 Wiley Periodicals, Inc.

Practical Stannylation of Allyl Acetates Catalyzed by Nickel with Bu3 SnOMe.

PubMed

Komeyama, Kimihiro; Itai, Yuuhei; Takaki, Ken

2016-06-27

A practical and scalable nickel-catalyzed allylic stannylation of allyl acetates with Bu3 SnOMe is described. A variety of acyclic and cyclic allyl acetates, even with base-sensitive moieties, undergoes the stannylation by using NiBr2 /4,4'-di-tert-butylbipyridine (dtbpy)/Mn catalyst system to afford highly functionalized allyl stannanes with excellent regioselectivity and yields. Furthermore, the scope of protocol is also extended by the reaction of propargyl acetates, giving rise to propargyl or allenyl stannanes. Additionally, a unique diastereoselectivity using the nickel catalyst different from the palladium was demonstrated for the stannylation of cyclic allyl acetates. In the reaction, inexpensive and stable nickel complexes, abundant reductant (Mn), and atom-economical stannyl source were used. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Myoglobin-Catalyzed Olefination of Aldehydes.

PubMed

Tyagi, Vikas; Fasan, Rudi

2016-02-12

The olefination of aldehydes constitutes a most valuable and widely adopted strategy for constructing carbon-carbon double bonds in organic chemistry. While various synthetic methods have been made available for this purpose, no biocatalysts are known to mediate this transformation. Reported herein is that engineered myoglobin variants can catalyze the olefination of aldehydes in the presence of α-diazoesters with high catalytic efficiency (up to 4,900 turnovers) and excellent E diastereoselectivity (92-99.9 % de). This transformation could be applied to the olefination of a variety of substituted benzaldehydes and heteroaromatic aldehydes, also in combination with different alkyl α-diazoacetate reagents. This work provides a first example of biocatalytic aldehyde olefination and extends the spectrum of synthetically valuable chemical transformations accessible using metalloprotein-based catalysts. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Facially Selective Cu-catalyzed Carbozincation of Cyclopropenes Using Arylzinc Reagents Formed by Sequential I/Mg/Zn exchange

PubMed Central

Tarwade, Vinod; Selvaraj, Ramajeyam; Fox, Joseph M.

2012-01-01

Described is a Cu-catalyzed directed carbozincation of cyclopropenes with organozinc reagents prepared by I/Mg/Zn exchange. This protocol broadens the scope with respect to functional group tolerance and enables use of aryl iodide precursors, rather than purified diorganozinc precursors. Critical to diastereoselectivity of the carbozincation step is the removal of magnesium halide salts after transmetallation with ZnCl2. PMID:23035947

Iron(II)-catalyzed intramolecular aminohydroxylation of olefins with functionalized hydroxylamines.

PubMed

Liu, Guan-Sai; Zhang, Yong-Qiang; Yuan, Yong-An; Xu, Hao

2013-03-06

A diastereoselective aminohydroxylation of olefins with a functionalized hydroxylamine is catalyzed by new iron(II) complexes. This efficient intramolecular process readily affords synthetically useful amino alcohols with excellent selectivity (dr up to > 20:1). Asymmetric catalysis with chiral iron(II) complexes and preliminary mechanistic studies reveal an iron nitrenoid is a possible intermediate that can undergo either aminohydroxylation or aziridination, and the selectivity can be controlled by careful selection of counteranion/ligand combinations.

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

PubMed Central

Röse, Philipp; Emge, Steffen; Yoshida, Jun-ichi

2015-01-01

Summary The cobalt(I)-catalysed 1,4-hydrovinylation reaction of allyloxytrimethylsilane and allyl alcohol with substituted 1,3-dienes leads to hydroxy-functionalised 1,4-dienes in excellent regio- and diastereoselective fashion. Those 1,4-dienols can be converted into tetrahydrofuran and pyran derivatives under indirect electrochemical conditions generating selenium or iodonium cations. The reactions proceed in good yields and regioselectivities for the formation of single diastereomers. PMID:25815067

The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizations

DOE PAGES

Hart-Cooper, William M.; Zhao, Chen; Triano, Rebecca M.; ...

2014-11-28

The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K 12Ga 4L 6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 10 5, which numbers among the largest magnitudesmore » of transition state stabilization measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity.« less

Palladium-Catalyzed Oxidative Couplings and Applications to the Synthesis of Macrocycles and Strained Cyclic Dienes

NASA Astrophysics Data System (ADS)

Boon, Byron Adrian

The palladium(II)-catalyzed oxidative macrocyclization of bis(vinylboronate esters) is demonstrated as an efficient method for the synthesis of macrocyclic dienes. The macrocyclization reactions feature mild conditions due to a palladium(II) catalytic cycle which obviates the need for a high energy oxidative addition step of standard palladium(0) catalytic cycles. Instead, this oxidative coupling is promoted by chloroacetone as a terminal re-oxidant in the catalytic cycle. An extension of the oxidative coupling/macrocyclization strategy is highlighted where molecular oxygen may be used in place of chloroacetone as the terminal re-oxidant. Homocoupling reactions of vinylboronate esters served as a template to screen reaction conditions for this method. From these experiments, multiple reaction conditions gave the oxidative homocoupling product in high yield. These reaction conditions were successfully applied to the oxidative macrocyclization of a bis(vinylboronate ester) using molecular oxygen as a re-oxidant. Syntheses of strained cyclic dienes were accomplished via the palladium(II)-catalyzed oxidative cyclizations of terminal bis(vinylboronate esters). The reactions generated strained (E,E)-1,3-dienes that underwent spontaneous 4?-electrocyclizations to form bicyclic cyclobutenes. Formation of the cyclobutenes is driven by strain in the medium-ring (E,E)-1,3-diene intermediates. Thermal ring openings of the cyclobutenes give (Z,Z)-1,3-diene products, again for thermodynamic reasons. These results are in contrast with typical acyclic trans-3,4-dialkyl cyclobutenes, which favor outward torquoselective ring-openings to give (E,E)-1,3-dienes. DFT calculations verified the thermodynamic versus kinetic control of the reactions and kinetic studies are in excellent agreement with the calculated energy changes. Investigations on the transannular Pauson-Khand reaction are also highlighted. The Pauson-Khand reaction is a powerful tool for the synthesis of cyclopentenones through the efficient [2+2+1] cycloaddition of dicobalt alkyne complexes with alkenes. While intermolecular and intramolecular variants are widely known, transannular versions of this reaction are unknown and the basis of this study. Our successful transannular Pauson-Khand reaction required a cyclic enyne incorporating one short three-membered linker chain and a rigid aryl linker in the backbone of the long linker chain. This rigidity of the aryl linker is proposed to facilitate the transannular [2+2+1] cyclization. Computational studies revealed that transannular Pauson-Khand reactions are thermodynamically favored for cyclic enynes featuring a long linker of at least 5 carbons, but with smaller chains the reactions are thermodynamically disfavored. Experimental studies show that long linking chains with more than 5 members are required to prevent to steric interactions between the dicobalt hexacarbonyl moiety and the linking chain to allow the reaction to be kinetically favored. The final part of this work highlights progress towards the total synthesis of (+)-kingianin A. This natural product was isolated as a racemic mixture from the bark of Endiandra kingiana and is an inhibitor of antiapoptotic protein Bcl-Xl, highlighting its potential use in cancer treatments. Its structure is proposed to arise from an intermolecular Diels-Alder dimerization reaction of bicyclo[4.2.0]octadiene fragments derived from an 8pi/6pi-electrocyclization cascade. Although two total syntheses of (+/-)-kingianin A have been reported, an enantioselective synthesis has not been achieved and is the purpose of this study. This synthetic route begins from L-(+)-dimethyl tartrate, a cheap and commercially available starting material, and aims to follow a biomimetic synthetic pathway featuring a substrate controlled diastereoselective palladium(II)-catalyzed oxidative cyclization and 8pi/6pi-electrocyclization cascade. Although the feasibility of this cascade pathway has not yet been realized, key synthetic transformations to install the requisite carbocyclic framework of (+)-kingianin A have been discovered, paving the way for future investigations on the palladium(II)-catalyzed coupling/electrocyclization cascade and completion of the synthesis.

Rhodium-Catalyzed Asymmetric Conjugate Alkynylation/Aldol Cyclization Cascade for the Formation of α-Propargyl-β-hydroxyketones.

PubMed

Choo, Ken-Loon; Lautens, Mark

2018-03-02

A rhodium-catalyzed conjugate alkynylation/aldol cyclization cascade was developed. Densely functionalized cyclic α-propargyl-β-hydroxyketones were synthesized with simultaneous formation of a C(sp)-C(sp 3 ) bond, a C(sp 3 )-C(sp 3 ) bond, as well as three new contiguous stereocenters. The transformation was achieved with excellent enantio- and diastereoselectivities using BINAP as the ligand. The synthetic utility of the newly installed alkynyl moiety was exhibited by subjecting the products to an array of derivatizations.

Ruthenium-catalyzed insertion of adjacent diol carbon atoms into C-C bonds: Entry to type II polyketides.

PubMed

Bender, Matthias; Turnbull, Ben W H; Ambler, Brett R; Krische, Michael J

2017-08-25

Current catalytic processes involving carbon-carbon bond activation rely on π-unsaturated coupling partners. Exploiting the concept of transfer hydrogenative coupling, we report a ruthenium(0)-catalyzed cycloaddition of benzocyclobutenones that functionalizes two adjacent saturated diol carbon-hydrogen bonds. These regio- and diastereoselective processes enable convergent construction of type II polyketide substructures. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Diastereoselective Additions of Allylmetal Reagents to Free and Protected syn-α,β-Dihydroxyketones Enable Efficient Synthetic Routes to Methyl Trioxacarcinoside A

PubMed Central

Smaltz, Daniel J.; Švenda, Jakub

2012-01-01

Two routes to the 2,6-dideoxysugar methyl trioxacarcinoside A are described. Each was enabled by an apparent α-chelation-controlled addition of an allylmetal reagent to a ketone substrate containing a free α-hydroxyl group and a β-hydroxyl substituent, either free or protected as the corresponding di-tert-butylmethyl silyl ether. Both routes provide practical access to gram-quantities of trioxacarcinose A in a form suitable for glycosidic coupling reactions. PMID:22404560

Remarkable biomimetic chemoselective aerobic oxidation of flavano-ellagitannins found in oak-aged wine.

PubMed

Petit, Emilie; Lefeuvre, Dorothée; Jacquet, Rémi; Pouységu, Laurent; Deffieux, Denis; Quideau, Stéphane

2013-10-25

Under the auspices of Bacchus! Acutissimins, natural flavano-ellagitannins, occur in oak-aged wine as a result of a diastereoselective condensation reaction of the flavan-3-ol catechin, a component of grapes, with the C-glucosidic ellagitannin vescalagin, found in oak. The acutissimins are further converted into natural mongolicains and analogues of camelliatannin G in a remarkably chemoselective fashion by simple aerobic oxidation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microwave-based reaction screening: tandem retro-Diels-Alder/Diels-Alder cycloadditions of o-quinol dimers.

PubMed

Dong, Suwei; Cahill, Katharine J; Kang, Moon-Il; Colburn, Nancy H; Henrich, Curtis J; Wilson, Jennifer A; Beutler, John A; Johnson, Richard P; Porco, John A

2011-11-04

We have accomplished a parallel screen of cycloaddition partners for o-quinols utilizing a plate-based microwave system. Microwave irradiation improves the efficiency of retro-Diels-Alder/Diels-Alder cascades of o-quinol dimers which generally proceed in a diastereoselective fashion. Computational studies indicate that asynchronous transition states are favored in Diels-Alder cycloadditions of o-quinols. Subsequent biological evaluation of a collection of cycloadducts has identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription factor.

Allyl transfer to aldehydes and ketones by Brønsted acid activation of allyl and crotyl 1,3,2-dioxazaborolidines.

PubMed

Reilly, Maureen K; Rychnovsky, Scott D

2010-11-05

Alkyl dioxazaborolidines are air-stable and often crystalline organoboranes. A variety of Brønsted acids activate allyl dioxazaborolidines to generate reactive allyl-transfer reagents in situ. These reagents add to aldehydes and ketones to generate the corresponding alcohols in good yields under mild conditions. The E- and Z-crotyl reagents react diastereoselectively with aldehydes and ketones to produce anti and syn adducts, respectively, a result consistent with a cyclic transition state (type I mechanism).

Isotope Effects and Mechanism of the Asymmetric BOROX Brønsted Acid Catalyzed Aziridination Reaction

PubMed Central

Vetticatt, Mathew J.; Desai, Aman A.; Wulff, William D.

2013-01-01

The mechanism of the chiral VANOL-BOROX Brønsted acid catalyzed aziridination reaction of imines and ethyldiazoacetate has been studied using a combination of experimental kinetic isotope effects and theoretical calculations. A stepwise mechanism where reversible formation of a diazonium ion intermediate precedes rate-limiting ring-closure to form the cis-aziridine is implicated. A revised model for the origin of enantio- and diastereoselectivity is proposed based on relative energies of the ring closing transition structures. PMID:23687986

Applications of Iridium-Catalyzed Asymmetric Allylic Substitution Reactions in Target-Oriented Synthesis.

PubMed

Qu, Jianping; Helmchen, Günter

2017-10-17

Metal catalyzed allylic substitution is a cornerstone of organometallic and synthetic chemistry. Enantioselective versions have been developed with catalysts derived from transition metals, most notably molybdenum, nickel, ruthenium, rhodium, iridium, palladium, and copper. The palladium- and the iridium-catalyzed versions have turned out to be particularly versatile in organic synthesis because of the very broad scope of the nucleophile and great functional group compatibility. Assets of the iridium-catalyzed reaction are the formation of branched, chiral products from simple monosubstituted allylic substrates, high degrees of regio- and enantioselectivity, and use of modular, readily available chiral ligands. The possibility to use carbon, nitrogen, oxygen, and sulfur compounds as well as fluoride as nucleophiles allows a wide range of chiral building blocks to be prepared. Our Account begins with the presentation of fundamental reaction schemes and chiral ligands. We will focus our discussion on reactions promoted by phosphoramidite ligands, though numerous chiral ligands have been employed. The subsequent section presents a brief overview of reaction mechanism and experimental conditions. Two versions of the iridium-catalyzed allylic substitution have emerged. In type 1 reactions (introduced in 1997), linear allylic esters are commonly used as substrates under basic reaction conditions. In type 2 reactions (introduced in 2007), environmentally friendly branched allylic alcohols can be reacted under acidic conditions; occasionally, derivatives of allylic alcohols have also been applied. A unique feature of the type 2 reactions is that highly electrophilic allylic intermediates can be brought to reaction with weakly activated alkenes. The subsequent text is ordered according to the strategies followed to transform allylic substitution products to desired targets, most of which are natural products or drugs. Syntheses starting with an intermolecular allylic substitution are discussed first. Some fairly complex targets, for example, the potent nitric oxide inhibitor (-)-nyasol and the drug (-)-protrifenbute, have been synthesized via less than five steps from simple starting materials. Most targets discussed are cyclic compounds. Intermolecular allylic substitution with subsequent ring closing metathesis is a powerful strategy for their synthesis. Highlights are stereodivergent syntheses of Δ 9 -tetrahydrocannabinols (THC), wherein iridium- and organocatalysis are combined (dual catalysis). The combination of allylic alkylation with a Diels-Alder reaction was utilized to synthesize the ketide apiosporic acid and the drug fesoterodine (Toviaz). Sequential allylic amination, hydroboration and Suzuki-Miyaura coupling generates enones suitable for conjugate addition reactions; this strategy was employed in syntheses of a variety of alkaloids, for example, the poison frog alkaloid (+)-cis-195A (pumiliotoxin C). Intramolecular substitutions offer interesting possibilities to build up stereochemical complexity via short synthetic routes. For example, in diastereoselective cyclizations of chiral compounds, substrate control can be overruled by catalyst control in order to generate cis- and trans-isomers selectively from a given precursor. This approach was used to prepare a variety of piperidine and pyrrolidine alkaloids. Finally, complex polycyclic structures, including the structurally unusual indolosesquiterpenoid mycoleptodiscin A, have been generated diastereo- and enantioselectively from olefins by polyene cyclizations and from electron-rich arenes, such as indoles, in dearomatization reactions.

Iron(II)-catalyzed intermolecular amino-oxygenation of olefins through the N-O bond cleavage of functionalized hydroxylamines.

PubMed

Lu, Deng-Fu; Zhu, Cheng-Liang; Jia, Zhen-Xin; Xu, Hao

2014-09-24

An iron-catalyzed diastereoselective intermolecular olefin amino-oxygenation reaction is reported, which proceeds via an iron-nitrenoid generated by the N-O bond cleavage of a functionalized hydroxylamine. In this reaction, a bench-stable hydroxylamine derivative is used as the amination reagent and oxidant. This method tolerates a range of synthetically valuable substrates that have been all incompatible with existing amino-oxygenation methods. It can also provide amino alcohol derivatives with regio- and stereochemical arrays complementary to known amino-oxygenation methods.

Microwave-Based Reaction Screening: Tandem Retro-Diels-Alder/Diels-Alder Cycloadditions of ortho-Quinol Dimers

PubMed Central

Dong, Suwei; Cahill, Kath arine J.; Kang, Moon -Il; Colburn, Nancy H.; Henrich, Curtis J.; Wilson, Jennifer A.; Beutler, John A.; Johnson, Richard P.; Porco, John A.

2011-01-01

We have accomplished a parallel screen of cycloaddition partners for ortho-quinols utilizing a plate-based microwave system. Microwave irradiation improves the efficiency of retro-Diels-Alder/Diels-Alder cascades of ortho-quinol dimers which generally proceed in a diastereoselective fashion. Computational studies indicate that asynchronous transition states are favored in Diels-Alder cycloadditions of ortho-quinols. Subsequent biological evaluation of a collection of cycloadducts has identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription factor. PMID:21942286

[1,5]-Anion relay via intramolecular proton transfer to generate 3,3-bis(silyl) allyloxy lithium: a useful scaffold for syn-addition to aldehydes and ketones.

PubMed

Lin, Xinglong; Ye, Xincui; Sun, Xianwei; Zhang, Yuebao; Gao, Lu; Song, Zhenlei

2014-02-21

A [1,5]-anion relay has been achieved in 3,3-bis(silyl) benzyl enol ether. Deprotonation at the sterically more accessible benzyl position triggers an intramolecular proton transfer to generate the thermodynamically more stable 3,3-bis(silyl) allyloxy lithium. This endo-oriented allyl anion is stable at -78 °C and undergoes diastereoselective syn-addition at the γ-position with aldehydes and ketones to give monobenzyl-substituted 1,2-diols.

Allyl Transfer to Aldehydes and Ketones by Brønsted Acid Activation of Allyl and Crotyl 1,3,2-Dioxazaborolidines

PubMed Central

Reilly, Maureen K.; Rychnovsky, Scott D.

2010-01-01

Alkyl dioxazaborolidines are air-stable and often crystalline organoboranes. A variety of Brønsted acids activate allyl dioxazaborolidines to generate reactive allyl-transfer reagents in situ. These reagents add to aldehydes and ketones to generate the corresponding alcohols in good yields under mild conditions. The E- and Z-crotyl reagents react diastereoselectively with aldehydes and ketones to produce anti and syn adducts, respectively, a result consistent with a cyclic transition state (Type I mechanism). PMID:20942379

Regio- and Stereoselective Cascades via Aldol Condensation and 1,3-Dipolar Cycloaddition for Construction of Functional Pyrrolizidine Derivatives.

PubMed

Mao, Zhuo-Ya; Liu, Yi-Wen; Han, Pan; Dong, Han-Qing; Si, Chang-Mei; Wei, Bang-Guo; Lin, Guo-Qiang

2018-02-16

An efficient and step-economical approach to access functionalized pyrrolizidine derivatives by a one-pot tandem sequence, including an aldol condensation and subsequent 1,3-dipolar cycloaddition process, has been developed, starting from acetone, aldehyde, and proline. A number of substituted aromatic aldehydes were amenable to this transformation, and the desired products, racemic 7a-7w and chiral 9a-9m, were obtained with excellent regioselectivities and outstanding diastereoselectivities. Moreover, in situ NMR studies revealed MgSO 4 could effectively promote the aldol condensation pathway in this tandem process.

Gemini analogs of vitamin D.

PubMed

Pazos, Gonzalo; Rivadulla, Marcos L; Pérez-García, Xenxo; Gandara, Zoila; Pérez, Manuel

2014-01-01

The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. This progression was possible due to improvements in the synthetic methods for the preparation of these derivatives, which allowed for increasing molecular complexity and complete diastereoselective control at C-20 and the substituted sidechains.

Remote Central-to-Axial Chirality Conversion: Direct Atroposelective Ester to Biaryl Transformation.

PubMed

Link, Achim; Sparr, Christof

2018-05-16

A strategy for the remote central-to-axial chirality conversion by simultaneous planarization of an encoding and a transient stereocenter is presented. Based on a diastereoselective double addition of a chiral 1,5-bifunctional organomagnesium alkoxide reagent to a broad range of aryl ester substrates, axially chiral biaryls are directly obtained upon in situ reduction. Various structurally distinct atropisomeric biaryl silanes that serve as valuable chiral biaryl anion surrogates are accessible in one step with e.r. values of up to 98:2. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diastereoselective intramolecular Ritter reaction: generation of a cis-fused hexahydro-4aH-indeno[1,2-b]pyridine ring system with 4a,9b-diangular substituents.

PubMed

Van Emelen, K; De Wit, T; Hoornaert, G J; Compernolle, F

2000-10-05

Indanol intermediates 5, prepared via Michael addition of 1-indanone beta-ketoester and acrylonitrile followed by reduction or Grignard reaction of the ketone group, were submitted to intramolecular Ritter reaction using various acid reaction conditions to produce tricyclic lactams 4. This cis-fused hexahydro-4aH-indeno[1,2-b]pyridine ring system, substituted at both angular positions 4a and 9b, provides access to constrained analogues of non-peptide NK(1)-antagonists with monocyclic piperidine structure.

Probing Competitive and Co-operative Hydroxyl and Ammonium Hydrogen-Bonding Directed Epoxidations.

PubMed

Brambilla, Marta; Brennan, Méabh B; Csatayová, Kristína; Davies, Stephen G; Fletcher, Ai M; Kennett, Alice M R; Lee, James A; Roberts, Paul M; Russell, Angela J; Thomson, James E

2017-10-06

The diastereoselectivities and rates of epoxidation (upon treatment with Cl 3 CCO 2 H then m-CPBA) of a range of cis- and trans-4-aminocycloalk-2-en-1-ol derivatives (containing five-, six-, and seven-membered rings) have been investigated. In all cases where the two potential directing groups can promote epoxidation on opposite faces of the ring scaffold, evidence of competitive epoxidation pathways, promoted by hydrogen-bonding to either the in situ formed ammonium moiety or the hydroxyl group, was observed. In contrast to the relative directing group abilities already established for the six-membered ring system (NHBn ≫ OH > NBn 2 ), an N,N-dibenzylammonium moiety appeared more proficient than a hydroxyl group at directing the stereochemical course of the epoxidation reaction in a five- or seven-membered system. In the former case, this was rationalized by the drive to minimize torsional strain in the transition state being coupled with assistance from hydrogen-bonding to the ammonium moiety. In the latter case, this was ascribed to the steric bulk of the ammonium moiety disfavoring conformations in which hydrogen-bonding to the hydroxyl group results in direction of the epoxidation to the syn face. In cases where the two potential directing groups can promote epoxidation on the same face of the ring scaffold, an enhancement of epoxidation diastereoselectivity was not observed, while introduction of a second, allylic heteroatom to the substrate results in diminishment of the rate of epoxidation in all cases. Presumably, reduction of the nucleophilicity of the olefin by the second, inductively electron-withdrawing heteroatom is the dominant factor, and any assistance to the epoxidation reaction by the potential to form hydrogen-bonds to two directing groups rather than one is clearly unable to overwhelm it.

Syntheses of the enantiomers of 1-deoxynojirimycin and 1-deoxyaltronojirimycin via chemo- and diastereoselective olefinic oxidation of unsaturated amines.

PubMed

Bagal, Sharan K; Davies, Stephen G; Lee, James A; Roberts, Paul M; Scott, Philip M; Thomson, James E

2010-12-03

Oxidation of enantiomerically pure (R)-N(1)-1'-(1''-naphthyl)ethyl-2,7-dihydro-1H-azepine with m-CPBA in the presence of HBF(4) and BnOH gave (3S,4R,5S,6S,1'R)-N(1)-1'-(1''-naphthyl)ethyl-3-hydroxy-4-benzyloxy-5,6-epoxyazepane as the major product and as a single diastereoisomer after chromatography. Elaboration of this highly functionalized intermediate via ring contraction to (2S,3R,4S,5S,1'R)-N(1)-benzyl-2-chloromethyl-3-benzyloxy-4,5-epoxypiperidine followed by regioselective epoxide ring opening, functional group manipulation, and deprotection gave (+)-1-deoxyaltronojirimycin. Alternatively, resolution of (RS,RS)-N(1)-benzyl-3-hydroxy-4-benzyloxy-2,3,4,7-tetrahydro-1H-azepine or (3RS,4SR,5RS,6RS)-N(1)-benzyl-3-hydroxy-4-benzyloxy-5,6-epoxyazepane by preparative chiral HPLC and subsequent elaboration allows access to the enantiomers of 1-deoxynojirimycin and 1-deoxyaltronojirimycin, respectively.

Macromolecular crowding-assisted fabrication of liquid-crystalline imprinted polymers.

PubMed

Zhang, Chen; Zhang, Jing; Huang, Yan-Ping; Liu, Zhao-Sheng

2015-04-01

A macromolecular crowding-assisted liquid-crystalline molecularly imprinted monolith (LC-MIM) was prepared successfully for the first time. The imprinted stationary phase was synthesized with polymethyl methacrylate (PMMA) or polystyrene (PS) as the crowding agent, 4-cyanophenyl dicyclohexyl propylene (CPCE) as the liquid-crystal monomer, and hydroquinidine as the pseudo-template for the chiral separation of cinchona alkaloids in HPLC. A low level of cross-linker (26%) has been found to be sufficient to achieve molecular recognition on the crowding-assisted LC-MIM due to the physical cross-linking of mesogenic groups in place of chemical cross-linking, and baseline separation of quinidine and quinine could be achieved with good resolution (R(s) = 2.96), selectivity factor (α = 2.16), and column efficiency (N = 2650 plates/m). In contrast, the LC-MIM prepared without crowding agents displayed the smallest diastereoselectivity (α = 1.90), while the crowding-assisted MIM with high level of cross-linker (80%) obtained the greatest selectivity factor (α = 7.65), but the lowest column efficiency (N = 177 plates/m).

Scalable Total Syntheses of N-Linked Tryptamine Dimers by Direct Indole-Aniline Coupling: Psychotrimine and Kapakahines B & F

PubMed Central

Newhouse, Timothy; Lewis, Chad A.; Eastman, Kyle J.; Baran, Phil S.

2010-01-01

This report details the invention of a method to enable syntheses of psychotrimine, 1, and the kapakahines F and B, 2 & 3, on a gram scale and in a minimum number of steps. Mechanistic inquiries are presented for the key enabling quaternization of indole at the C3 position by electrophilic attack of an activated aniline species. Excellent chemo-, regio-, and diastereoselectivities are observed for reactions with o-iodoaniline, an indole cation equivalent. Additionally, the scope of this reaction is broad with respect to the tryptamine and aniline components. The anti-cancer profiles of psychotrimine, 1, and kapakahines F and B, 2 & 3, have also been evaluated. PMID:20426477

Pseudoephedrine-Directed Asymmetric α-Arylation of α-Amino Acid Derivatives.

PubMed

Atkinson, Rachel C; Fernández-Nieto, Fernando; Mas Roselló, Josep; Clayden, Jonathan

2015-07-27

Available α-amino acids undergo arylation at their α position in an enantioselective manner on treatment with base of N'-aryl urea derivatives ligated to pseudoephedrine as a chiral auxiliary. In situ silylation and enolization induces diastereoselective migration of the N'-aryl group to the α position of the amino acid, followed by ring closure to a hydantoin with concomitant explulsion of the recyclable auxiliary. The hydrolysis of the hydantoin products provides derivatives of quaternary amino acids. The arylation avoids the use of heavy-metal additives, and is successful with a range of amino acids and with aryl rings of varying electronic character. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Atropisomerism about Aryl-C(sp(3)) Bonds: Conformational Behavior of Substituted Phenylcyclohexanes in Solution.

PubMed

Flos, Manon; Lameiras, Pedro; Denhez, Clément; Mirand, Catherine; Berber, Hatice

2016-03-18

A catalytic hydrogenation of cannabidiol derivatives known as phenylcyclohexenes was used to prepare epimeric (1R,1S) and/or rotameric (M,P) phenylcyclohexanes. The reaction is diastereoselective, in favor of the 1S epimer, when large groups are attached to the phenyl ring. For each epimer, variable-temperature NMR experiments, including EXSY spectroscopy and DFT calculations, were used to determine the activation energies of the conformational exchange arising from the restricted rotation about the aryl-C(sp(3)) bond that led to two unequally populated rotamers. The conformational preference arises essentially from steric interactions between substituents vicinal to the pivot bond. The conformers of epimers (1S)-2e,f show high rotational barriers of up to 92 kJ mol(-1), unlike those of (1R)-2e,f and with much lower barriers of ∼72 kJ mol(-1). The height of the barriers not only depends on the substituents at the axis of chirality but also is influenced by the position of a methyl group on the monoterpene ring. The feature most favorable to high rotational barriers is when the methyl at C1 lies equatorially. This additional substituent effect, highlighted for the first time, seems fundamental to allowing atropisomerism in hindered ortho-substituted phenylcyclohexanes.

Experimental and Theoretical Studies on the Nazarov Cyclization/Wagner-Meerwein Rearrangement Sequence

PubMed Central

Lebœuf, David; Ciesielski, Jennifer

2012-01-01

Highly functionalized cyclopentenones can be generated stereospecifically by a chemoselective copper(II)-mediated Nazarov/Wagner-Meerwein rearrangement sequence of divinyl ketones. A detailed investigation of this sequence is described including a study of substrate scope and limitations. After the initial 4π electrocyclization, this reaction proceeds via two different sequential [1,2]-shifts, with selectivity that depends upon either migratory ability or the steric bulkiness of the substituents at C1 and C5. This methodology allows the creation of vicinal stereogenic centers, including adjacent quaternary centers. This sequence can also be achieved by using a catalytic amount of copper(II) in combination with NaBAr4f, a weak Lewis acid. During the study of the scope of the reaction, a partial or complete E / Z isomerization of the enone moiety was observed in some cases prior to the cyclization, which resulted in a mixture of diastereomeric products. Use of a Cu(II)-bisoxazoline complex prevented the isomerization, allowing high diastereoselectivity to be obtained in all substrate types. In addition, the reaction sequence was studied by DFT computations at the UB3LYP/6-31G(d,p) level, which are consistent with the proposed sequences observed, including E / Z isomerizations and chemoselective Wagner-Meerwein shifts. PMID:22471833

Fungal Biodegradative Oxidants in Lignocellulose: Fluorescence Mapping and Correlation With Gene Expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammel, Kenneth E.; Ralph, John; Hunt, Christopher G.

This work focused on new methods for the detection of oxidation in natural substrates during the deconstruction of lignocellulose by microoganisms. Oxidation was the focus because all known biological systems that degrade lignin are oxidative. The detection methods involved the used of (a) micrometer-scale beads carrying a fluorescent dye that is sensitive to oxidation, (b) 13C-labeled synthetic lignins whose breakdown products can be assessed using mass spectrometry and nuclear magnetic resonance spectroscopy, and (c) a fluorometric stain that is highly sensitive to incipient oxidation during microbial attack. The results showed (a) that one white rot fungus, Phanerochaete chrysosporium, produces diffusiblemore » oxidants on wood, and that the onset of oxidation is coincident with the marked up-regulation of genes that encode ligninolytic peroxidases and auxiliary oxidative enzymes; (b) that a more selectively ligninolytic white rot fungus, Ceriporiopsis subvermispora, produces a highly diastereoselective oxidative system for attack on lignin; (c) that a brown rot fungus, Serpula lacrymans, uses extracellular hydroquinone metabolites to drive the production of lignocellulose-oxidizing free radicals; (d) that both white rot and brown rot fungi produce highly diffusible mild oxidants that modify lignocellulose at the earliest stage of substrate deconstruction; and (e) that lignin degradation in a tropical soil is not inhibited as much as expected during periods of flooding-induced hypoxia, which indicates that unknown mechanisms for attack on lignin remain to be discovered.« less

Recent developments in the metal-catalyzed reactions of metallocarbenoids from propargylic esters.

PubMed

Marco-Contelles, José; Soriano, Elena

2007-01-01

The transition-metal-catalyzed intramolecular cycloisomerization of propargylic carboxylates provides functionalized bicyclo[n.1.0]enol esters in a very diastereoselective manner and, depending on the structure, with partial or complete transfer of chirality from enantiomerically pure precursors. The subsequent methanolysis gives bicyclo[n.1.0] ketones, hence resulting in a very efficient two-step protocol for the syntheses of alpha,beta-unsaturated cyclopropyl ketones, key intermediates for the preparation of natural products. The results from mechanistic computational studies suggest that they probably proceed through cyclopropyl metallocarbenoids, formed by endo-cyclopropanation, that undergo a 1,2-acyl migration. Finally, the potential of the intermolecular reaction and the related pentannulation of propargylic esters bearing pendant aromatic rings are also discussed.

New insights into aldol reactions of methyl isocyanoacetate catalyzed by heterogenized homogeneous catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Rong; Zhao, Jie; Yuan, Bing

The Hayashi–Ito aldol reaction of methyl isocyanoacetate (MI) and benzaldehydes, a classic homogeneous Au(I)-catalyzed reaction, was studied with heterogenized homogeneous catalysts. Among dendrimer encapsulated nanoparticles (NPs) of Au, Pd, Rh, or Pt loaded in mesoporous supports and the homogeneous analogues, the Au NPs led to the highest yield and highest diastereoselectivity of products in toluene at room temperature. The Au catalyst was stable and was recycled for at least six runs without substantial deactivation. Moreover, larger pore sizes of the support and the use of a hydrophobic solvent led to a high selectivity for the trans diastereomer of the product.more » The activation energy is sensitive to neither the size of Au NPs nor the support. A linear Hammett plot was obtained with a positive slope, suggesting an increased electron density on the carbonyl carbon atom in the rate-limiting step. As a result, IR studies revealed a strong interaction between MI and the gold catalyst, supporting the proposed mechanism, in which rate-limiting step involves an electrophilic attack of the aldehyde on the enolate formed from the deprotonated MI.« less

New insights into aldol reactions of methyl isocyanoacetate catalyzed by heterogenized homogeneous catalysts

DOE PAGES

Ye, Rong; Zhao, Jie; Yuan, Bing; ...

2016-12-14

The Hayashi–Ito aldol reaction of methyl isocyanoacetate (MI) and benzaldehydes, a classic homogeneous Au(I)-catalyzed reaction, was studied with heterogenized homogeneous catalysts. Among dendrimer encapsulated nanoparticles (NPs) of Au, Pd, Rh, or Pt loaded in mesoporous supports and the homogeneous analogues, the Au NPs led to the highest yield and highest diastereoselectivity of products in toluene at room temperature. The Au catalyst was stable and was recycled for at least six runs without substantial deactivation. Moreover, larger pore sizes of the support and the use of a hydrophobic solvent led to a high selectivity for the trans diastereomer of the product.more » The activation energy is sensitive to neither the size of Au NPs nor the support. A linear Hammett plot was obtained with a positive slope, suggesting an increased electron density on the carbonyl carbon atom in the rate-limiting step. As a result, IR studies revealed a strong interaction between MI and the gold catalyst, supporting the proposed mechanism, in which rate-limiting step involves an electrophilic attack of the aldehyde on the enolate formed from the deprotonated MI.« less

Flow “Fine” Synthesis: High Yielding and Selective Organic Synthesis by Flow Methods

PubMed Central

2015-01-01

Abstract The concept of flow “fine” synthesis, that is, high yielding and selective organic synthesis by flow methods, is described. Some examples of flow “fine” synthesis of natural products and APIs are discussed. Flow methods have several advantages over batch methods in terms of environmental compatibility, efficiency, and safety. However, synthesis by flow methods is more difficult than synthesis by batch methods. Indeed, it has been considered that synthesis by flow methods can be applicable for the production of simple gasses but that it is difficult to apply to the synthesis of complex molecules such as natural products and APIs. Therefore, organic synthesis of such complex molecules has been conducted by batch methods. On the other hand, syntheses and reactions that attain high yields and high selectivities by flow methods are increasingly reported. Flow methods are leading candidates for the next generation of manufacturing methods that can mitigate environmental concerns toward sustainable society. PMID:26337828

Structural diversification of the aminobicyclo[4.3.0]nonane skeleton using alkynylsilyl-derived allylic trichloroacetimidates.

PubMed

Mostafa, Mohamed A B; McMillan, Angus E; Sutherland, Andrew

2017-04-05

The amino substituted bicyclo[4.3.0]nonane is a molecular scaffold found in a wide range of natural products and medicinal agents. Despite this, synthetic methods for the general preparation of this structural motif are sparse. Here we evaluate a diastereoselective approach for the preparation of vinylsilyl derived aminobicyclo[4.3.0]nonanes using a one-pot multi-bond forming process involving a Pd(ii)-catalysed Overman rearrangement, a Ru(ii)-catalysed ring closing enyne metathesis reaction, followed by a hydrogen bonding directed Diels-Alder reaction. We show that a benzyldimethylsilyl-substituted alkene analogue is amenable to further functionalisation and the late stage generation of diverse sp 3 -rich, drug-like aminobicyclo[4.3.0]nonane scaffolds with up to six stereogenic centres.

C-glycosylation reactions of sulfur-substituted glycosyl donors: evidence against the role of neighboring-group participation.

PubMed

Beaver, Matthew G; Billings, Susan B; Woerpel, K A

2008-02-13

Nucleophilic substitution reactions of C-4 sulfur-substituted tetrahydropyran acetals revealed that neighboring-group participation does not control product formation. Spectroscopic evidence for the formation of an intermediate sulfonium ion is provided, as are data from nucleophilic substitution reactions demonstrating that products are formed from oxocarbenium ion intermediates. The selectivity was not sensitive to solvent or to which Lewis acid was employed. The identity of the heteroatom at the C-4 position also did not significantly impact diastereoselectivity. Consequently, neighboring-group participation was not responsible for the formation of either the major or the minor products. These studies implicate a Curtin-Hammett kinetic scenario in which the formation of a low-energy intermediate does not necessitate its involvement in the product-forming pathway.

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

PubMed Central

2010-01-01

Summary The development of efficient Friedel–Crafts alkylations of arenes and heteroarenes using only catalytic amounts of a Lewis acid has gained much attention over the last decade. The new catalytic approaches described in this review are favoured over classical Friedel–Crafts conditions as benzyl-, propargyl- and allyl alcohols, or styrenes, can be used instead of toxic benzyl halides. Additionally, only low catalyst loadings are needed to provide a wide range of products. Following a short introduction about the origin and classical definition of the Friedel–Crafts reaction, the review will describe the different environmentally benign substrates which can be applied today as an approach towards greener processes. Additionally, the first diastereoselective and enantioselective Friedel–Crafts-type alkylations will be highlighted. PMID:20485588

Phosphine-substrate recognition through the C-H...O hydrogen bond: application to the asymmetric Pauson-Khand reaction.

PubMed

Solà, Jordi; Riera, Antoni; Verdaguer, Xavier; Maestro, Miguel A

2005-10-05

A unique methine moiety attached to three heteroatoms (O, P, S) and contained in the PuPHOS and CamPHOS ligands serves as a strong hydrogen-bond donor. Nonclassical hydrogen bonding of this methine with an amido-carbonyl acceptor provides a completely diastereoselective ligand exchange process between an alkyne dicobalthexacarbonyl complex and a phosphine ligand. This weak contact has been studied by means of X-ray analysis, 1H NMR, and quantum mechanical calculations and revealed that the present interaction falls in the range of strong C-H...O=C bonds. The hydrogen-bond bias obtained in the ligand exchange process has been exploited in the asymmetric intermolecular Pauson-Khand reaction to yield the corresponding cyclization adducts in up to 94% ee.

Iridium-mediated isomerization-cyclization of bicyclic Pauson-Khand derived allylic alcohols.

PubMed

Kavanagh, Yvonne; Chaney, Cíara M; Muldoon, Jimmy; Evans, Paul

2008-11-07

Treatment of 2-(toluene-4-sulfonyl)-2,3,4,4a,5,6-hexahydro-1H-[2]pyrindin-6-ol 10, accessed from the diastereoselective Luche reduction of a Pauson-Khand derived bicylic cyclopentenone, with a catalytic amount of (1,5-cyclooctadiene)(pyridine)(tricyclohexylphosphine)iridium(I) hexafluorophosphate 1 (Crabtree's catalyst) under a hydrogen atmosphere resulted in the formation of 4-(toluene-4-sulfonyl)-2-oxa-4-azatricyclo[5.2.1.0(3,8)]decane 12 as a single diastereoisomer. This process is likely to proceed via an initial Ir(I)-mediated isomerization of the alkene to form an N-sulfonyl enamine 11, followed by cyclization. Evidence to support this came when, after short reaction periods, 11 was isolated, characterized spectroscopically, and on resubmission to the reaction conditions formed 12.

Cyclopropylamines from N,N-dialkylcarboxamides and Grignard reagents in the presence of titanium tetraisopropoxide or methyltitanium triisopropoxide.

PubMed

de Meijere, Armin; Chaplinski, Vladimir; Winsel, Harald; Kordes, Markus; Stecker, Björn; Gazizova, Vesta; Savchenko, Andrei I; Boese, Roland; Schill, Farina

2010-12-10

Thirty-three different N,N-dialkyl- and N-alkyl-N-phosphorylalkyl-substituted carboxamides 9-17 were treated with unsubstituted as well as with 2-alkyl-, 2,2-dialkyl-, and 3-alkenyl-substituted ethylmagnesium bromides 6 in the presence of stoichiometric amounts of titanium tetraisopropoxide or methyltitanium triisopropoxide to furnish substituted cyclopropylamines 20-25 in 20-98% yield, depending on the substituents with no (1:1) to excellent (>25:1) diastereoselectivities. Generally higher yields (up to 98%) of the cyclopropylamines 20-28 without loss of the diastereoselectivity were obtained with methyltitanium triisopropoxide as the titanium mediator. Under these conditions, even dioxolane-protected ketones and halogen-substituted and chiral as well as achiral alkyloxyalkyl-substituted carboxamides could be converted to the correspondingly substituted cyclopropylamines with unsubstituted as well as phenyl- and a variety of alkyl-substituted ethylmagnesium bromides in addition to numerous heteroatom-containing (e.g., halogen-, trityloxy-, tetrahydropyranyloxy-substituted) Grignard reagents (62 examples altogether). The transformation of N,N-diformylalkylamines 54 with ethylmagnesium bromide in the presence of methyltitanium triisopropoxide to N,N-dicyclopropyl-N-alkylamines 55 can be brought about in up to 82% yield (6 examples). An asymmetric variant of the titanium-mediated cyclopropanation of N,N-dialkylcarboxamides has been developed by applying chiral titanium mediators generated from stoichiometric amounts of titanium tetraisopropoxide and chiral diamino or diol ligands, respectively. The most efficient chiral mediators turned out to be titanium bistaddolates that provided the corresponding cyclopropylamines with enantiomeric excesses (ee) of up to 84%. Evaluation of several silyl-based additives revealed that the reaction can also efficiently be carried out with substoichiometric amounts (down to 25 mol%) of the titanium reagent, as long as 2-aryl- or 2-ethenyl-substituted ethylmagnesium halides are used and a concomitant slight decrease in yields is accepted. The newly developed methodology was successfully applied for the preparation of analogues with cyclopropylamine moieties of known drugs and natural products such as the nicotine metabolite (S)-Cotinine as well as the insecticides Dinotefuran and Imidacloprid.

The growing impact of lyophilized cell-free protein expression systems

PubMed Central

Hunt, J. Porter; Yang, Seung Ook; Wilding, Kristen M.; Bundy, Bradley C.

2017-01-01

ABSTRACT Recently reported shelf-stable, on-demand protein synthesis platforms are enabling new possibilities in biotherapeutics, biosensing, biocatalysis, and high throughput protein expression. Lyophilized cell-free protein expression systems not only overcome cold-storage limitations, but also enable stockpiling for on-demand synthesis and completely sterilize the protein synthesis platform. Recently reported high-yield synthesis of cytotoxic protein Onconase from lyophilized E. coli extract preparations demonstrates the utility of lyophilized cell-free protein expression and its potential for creating on-demand biotherapeutics, vaccines, biosensors, biocatalysts, and high throughput protein synthesis. PMID:27791452

Allene formation by gold catalyzed cross-coupling of masked carbenes and vinylidenes

PubMed Central

Lavallo, Vincent; Frey, Guido D.; Kousar, Shazia; Donnadieu, Bruno; Bertrand, Guy

2007-01-01

Addition of a sterically demanding cyclic (alkyl)(amino)carbene (CAAC) to AuCl(SMe2) followed by treatment with [Et3Si(Tol)]+[B(C6F5)4]− in toluene affords the isolable [(CAAC)Au(η2-toluene)]+[B(C6F5)4]− complex. This cationic Au(I) complex efficiently mediates the catalytic coupling of enamines and terminal alkynes to yield allenes and not propargyl amines as observed with other catalysts. Mono-, di-, and tri-substituted enamines can be used, as well as aryl-, alkyl-, and trimethylsilyl-substituted terminal alkynes. The reaction tolerates sterically hindered substrates and is diastereoselective. This general catalytic protocol directly couples two unsaturated carbon centers to form the three-carbon allenic core. The reaction most probably proceeds through an unprecedented “carbene/vinylidene cross-coupling.” PMID:17698808

Access to benzo-fused nine-membered heterocyclic alkenes with a trifluoromethyl carbinol moiety via a double decarboxylative formal ring-expansion process under palladium catalysis† †Electronic supplementary information (ESI) available: CCDC 1575063, 1575065, 1575062, 1589030. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc05447e

PubMed Central

Das, Pulakesh; Gondo, Satoshi; Nagender, Punna; Uno, Hiroto; Tokunaga, Etsuko

2018-01-01

Direct access to pharmaceutically attractive benzo-fused nine-membered heterocyclic alkenes 3 with a trifluoromethyl carbinol moiety was achieved via a palladium-catalyzed double-decarboxylative formal ring-expansion process from six-membered trifluoromethyl benzo[d][1,3]oxazinones 1 to nine-membered trifluoromethyl benzo[c][1,5]oxazonines 3 in the presence of vinylethylene carbonates 2. Generation of a Pd-π-allyl zwitterionic intermediate was proposed in the catalytic cycle. The trifluoromethyl group in the benzoxazinanones 1 plays an important role throughout the transformation. Diastereoselective chemical transformations of products 3 were also demonstrated. PMID:29732106

The chemistry of wine polyphenolic C-glycosidic ellagitannins targeting human topoisomerase II.

PubMed

Quideau, Stéphane; Jourdes, Michael; Lefeuvre, Dorothée; Montaudon, Danièle; Saucier, Cédric; Glories, Yves; Pardon, Patrick; Pourquier, Philippe

2005-11-04

Polyphenolic nonahydroxyterphenoyl-containing C-glycosidic oak ellagitannins are found in wine as a result of the aging of this beverage in oak-made barrels. Once in the slightly acidic wine (pH approximately 3-4), some of these complex natural products such as (-)-vescalagin (1), but not its C-1 epimer (-)-castalagin (2), can capture grape-derived nucleophilic entities such as ethanol, the flavanols catechin (10a) and epicatechin (10b), the anthocyanin oenin (13b), and the thiolic glutathione (16) to furnish condensation products with retention of configuration at the C-1 locus. A computer-aided rationale of this high diastereoselectivity is given. These condensation products can contribute to the modulation of organoleptic properties of the wine, as evidenced by the 23 nm bathochromic shift color absorbance observed with the novel oenin-based anthocyano-ellagitannin (15b). Hydrolysis of 1 under solvolytic conditions furnished another novel compound that we refer to as vescalene (21), in addition to the known (-)-vescalin (18). Of pharmacological importance is the fact that most of these found-in-wine water-soluble ellagitannin derivatives are much more potent than etoposide (VP-16) at inhibiting top2-mediated DNA decatenation in vitro (top2=topoisomerase II)). The known (-)-vescalin (18) and the novel vescalene (21) fully inhibited top2 at 10 microM concentration!

Enantioselective Total Syntheses of FR901464 and Spliceostatin A and Evaluation of Splicing Activity of Key Derivatives

PubMed Central

2015-01-01

FR901464 (1) and spliceostatin A (2) are potent inhibitors of spliceosomes. These compounds have shown remarkable anticancer activity against multiple human cancer cell lines. Herein, we describe efficient, enantioselective syntheses of FR901464, spliceostatin A, six corresponding diastereomers and an evaluation of their splicing activity. Syntheses of spliceostatin A and FR901464 were carried out in the longest linear sequence of 9 and 10 steps, respectively. To construct the highly functionalized tetrahydropyran A-ring, we utilized CBS reduction, Achmatowicz rearrangement, Michael addition, and reductive amination as key steps. The remarkable diastereoselectivity of the Michael addition was specifically demonstrated with different substrates under various reaction conditions. The side chain B was prepared from an optically active alcohol, followed by acetylation and hydrogenation over Lindlar’s catalyst. The other densely functionalized tetrahydropyran C-ring was derived from readily available (R)-isopropylidene glyceraldehyde through a route featuring 1,2-addition, cyclic ketalization, and regioselective epoxidation. These fragments were coupled together at a late stage through amidation and cross-metathesis in a convergent manner. Six key diastereomers were then synthesized to probe the importance of specific stereochemical features of FR901464 and spliceostatin A, with respect to their in vitro splicing activity. PMID:24873648

An efficient protocol for the synthesis of highly sensitive indole imines utilizing green chemistry: optimization of reaction conditions.

PubMed

Nisar, Bushra; Rubab, Syeda Laila; Raza, Abdul Rauf; Tariq, Sobia; Sultan, Ayesha; Tahir, Muhammad Nawaz

2018-04-11

Novel and highly sensitive indole-based imines have been synthesized. Their synthesis has been compared employing a variety of protocols. Ultimately, a convenient, economical and high yielding set of conditions employing green chemistry have been designed for their synthesis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moorhouse, Saul J.; Wu, Yue; O’Hare, Dermot, E-mail: dermot.ohare@chem.ox.ac.uk

A newly developed in situ monochromatic high-energy X-ray diffraction setup was used to investigate the synthesis of MOFs using cation-impregnated polymer resin beads as a ion source. The Co–NDC–DMF (NDC=2,6-naphthalenedicarboxylate; DMF=dimethylformamide) system was investigated, a system which is known to produce at least three distinct frameworks. It was found that the resin-assisted synthesis results in the preferential formation of a topology previously impossible to synthesise in bulk, while the comparable nitrate-salt synthesis appeared to form an alternative phases. It was also found that the resin-assisted synthesis is highly diffusion-controlled. - Graphical abstract: In situ monochromatic high-energy X-ray diffraction study ofmore » a MOF synthesis. - Highlights: • Resin-assisted solvothermal MOF synthesis was studied using in situ diffraction. • Full kinetics of reaction can be obtained from in situ data. • Kinetics show that this resin-assisted synthesis is diffusion controlled. • Resin-assisted synthesis enables the production of an alternative bulk phase.« less

Hydrodynamic Effects in Soft-matter Self-assembly: The Case of J-Aggregates of Amphiphilic Porphyrins.

PubMed

Ribo, Josep M; El-Hachemi, Zoubir; Arteaga, Oriol; Canillas, Adolf; Crusats, Joaquim

2017-07-01

Chiral J-aggregates of achiral amphiphilic porphyrins (4-sulfonatophenyl and aryl meso-substituted porphyrins) show several effects under the hydrodynamic forces of common stirring. These effects can be classified as pure mechanic (e. g. elasticity, plasticity and breaking of the self-assembly non-covalent bonding) and chemically selective as detected in the formation/growth of the nanoparticles. Diastereoselective, enantioselective and, depending on the sign of chiral shear forces, even enantiospecific selections have been described. Some types of these effects have been reported in other type of J-aggregates. Reversible and irreversible structural effects have been studied by atomic force imaging. The determination of the optical polarization properties (linear and circular) of their solutions is best done using Mueller matrix polarimetry methods. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of hydroxylamine conformation on stereocontrol in Pd-catalyzed isoxazolidine-forming reactions.

PubMed

Lemen, Georgia S; Giampietro, Natalie C; Hay, Michael B; Wolfe, John P

2009-03-20

Palladium-catalyzed carboamination reactions between N-Boc-O-(but-3-enyl)hydroxylamine derivatives and aryl or alkenyl bromides afford cis-3,5- and trans-4,5-disubstituted isoxazolidines in good yield with up to >20:1 dr. The diastereoselectivity observed in the formation of cis-3,5-disubstituted isoxazolidines is superior to selectivities typically obtained in other transformations, such as 1,3-dipolar cycloaddition reactions, that provide these products. In addition, the stereocontrol in the C-N bond-forming Pd-catalyzed carboamination reactions of N-Boc-O-(but-3-enyl)hydroxylamines is significantly higher than that of related C-O bond-forming carboetherification reactions of N-benzyl-N-(but-3-enyl)hydroxylamine derivatives. This is likely due to a stereoelectronic preference for cyclization via transition states in which the Boc group is placed in a perpendicular orientation relative to the plane of the developing ring, which derives from the conformational equilibria of substituted hydroxylamines.

Enantioselective synthesis of α-oxy amides via Umpolung amide synthesis.

PubMed

Leighty, Matthew W; Shen, Bo; Johnston, Jeffrey N

2012-09-19

α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids.

Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment.

PubMed

Newsom, Sean A; Miller, Benjamin F; Hamilton, Karyn L; Ehrlicher, Sarah E; Stierwalt, Harrison D; Robinson, Matthew M

2017-11-01

Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to restore insulin sensitivity compared with nonenriched control low-fat or high-fat diets. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during weeks 10-12 High-resolution respirometry was performed using palmitoyl-l-carnitine, glutamate+malate, and glutamate+malate+succinate as substrates for mitochondria isolated from quadriceps. Mitochondrial protein synthesis and palmitoyl- l-carnitine oxidation were increased in mice consuming a high-fat diet, regardless of differences in insulin sensitivity with pioglitazone treatment. There was no effect of diet or pioglitazone treatment on ADP-stimulated respiration or H 2 O 2 emission using glutamate+malate or glutamate+malate+succinate. The results demonstrate no impairments to mitochondrial protein synthesis or respiration following induction of insulin resistance. Instead, mitochondrial protein synthesis was increased with a high-fat diet and may contribute to remodeling of the mitochondria to increase lipid oxidation capacity. Mitochondrial adaptations with a high-fat diet appear driven by nutrient availability, not intrinsic defects that contribute to insulin resistance. Copyright © 2017 the American Physiological Society.

Very High Performance High Nitrogen Energetic Ingredients and Energetic Polymers for Structural Components

DTIC Science & Technology

2011-12-31

have developed a vastly improved procedure for synthesis of the n- propyl ester that gives essentially quantitative yield and uses concentrated... Synthesis of n- propyl 4-aminofurazan-3-carboxylate. We next turned our attention to the synthesis of the amide. Again, the literature procedure is... synthesis and chemistry of 3-hydroxymethyl-4-amino[1,2,5]oxadiazole and 5) work on energetic polymers for structural components. 15. SUBJECT TERMS

Enantioselective Synthesis of α-Oxy Amides via Umpolung Amide Synthesis

PubMed Central

Leighty, Matthew W.; Shen, Bo

2012-01-01

α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes, and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids. PMID:22967461

New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity γ-Hydroxybutyrate (GHB) Binding Sites

PubMed Central

Vogensen, Stine B.; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H.F.; Clausen, Rasmus P.

2013-01-01

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Origin of Stereodivergence in Cooperative Asymmetric Catalysis with Simultaneous Involvement of Two Chiral Catalysts.

PubMed

Bhaskararao, Bangaru; Sunoj, Raghavan B

2015-12-23

Accomplishing high diastereo- and enantioselectivities simultaneously is a persistent challenge in asymmetric catalysis. The use of two chiral catalysts in one-pot conditions might offer new avenues to this end. Chirality transfer from a catalyst to product gets increasingly complex due to potential chiral match-mismatch issues. The origin of high enantio- and diastereoselectivities in the reaction between a racemic aldehyde and an allyl alcohol, catalyzed by using axially chiral iridium phosphoramidites PR/S-Ir and cinchona amine is established through transition-state modeling. The multipoint contact analysis of the stereocontrolling transition state revealed how the stereodivergence could be achieved by inverting the configuration of the chiral catalysts that are involved in the activation of the reacting partners. While the enantiocontrol is identified as being decided in the generation of PR/S-Ir-π-allyl intermediate from the allyl alcohol, the diastereocontrol arises due to the differential stabilizations in the C-C bond formation transition states. The analysis of the weak interactions in the transition states responsible for chiral induction revealed that the geometric disposition of the quinoline ring at the C8 chiral carbon of cinchona-enamine plays an anchoring role. The quinolone ring is noted as participating in a π-stacking interaction with the phenyl ring of the Ir-π-allyl moiety in the case of PR with the (8R,9R)-cinchona catalyst combination, whereas a series of C-H···π interactions is identified as vital to the relative stabilization of the stereocontrolling transition states when PR is used with (8S,9S)-cinchona.

An efficient synthesis strategy for metal-organic frameworks: Dry-gel synthesis of MOF-74 framework with high yield and improved performance

DOE PAGES

Das, Atanu Kumar; Vemuri, Rama Sesha; Kutnyakov, Igor; ...

2016-06-16

Here, vapor-assisted dry-gel synthesis of MOF-74 structure, specifically NiMOF-74 from its synthetic precursors, was conducted with high yield and improved performance showing promise for gas (CO 2) and water adsorption applications. Unlike conventional synthesis, which takes 72 h, this kinetic study showed that NiMOF-74 forms within 12 h under dry-gel conditions with similar performance characteristics and exhibits the best performance characteristics after 48 h of heating.

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

Photochemical approaches to ordered polymers

NASA Technical Reports Server (NTRS)

Meador, Michael A.; Abdulaziz, Mahmoud; Meador, Mary Ann B.

1990-01-01

The photocyclization of o-benzyloxyphenyl ketone chromophores provides an efficient, high yield route to the synthesis of 2,3-diphenylbenzofurans. The synthesis and solution of photochemistry of a series of polymers containing this chromophore is described. The photocuring of these polymers is a potential new approach to the synthesis of highly conjugated polymers based upon a p-phenylene bisbenzofuran repeat unit.

Synthesis of ultrathin nitrogen-doped graphitic carbon nanocages as advanced electrode materials for supercapacitor.

PubMed

Tan, Yueming; Xu, Chaofa; Chen, Guangxu; Liu, Zhaohui; Ma, Ming; Xie, Qingji; Zheng, Nanfeng; Yao, Shouzhuo

2013-03-01

Synthesis of nitrogen-doped carbons with large surface area, high conductivity, and suitable pore size distribution is highly desirable for high-performance supercapacitor applications. Here, we report a novel protocol for template synthesis of ultrathin nitrogen-doped graphitic carbon nanocages (CNCs) derived from polyaniline (PANI) and their excellent capacitive properties. The synthesis of CNCs involves one-pot hydrothermal synthesis of Mn3O4@PANI core-shell nanoparticles, carbonization to produce carbon coated MnO nanoparticles, and then removal of the MnO cores by acidic treatment. The CNCs prepared at an optimum carbonization temperature of 800 °C (CNCs-800) have regular frameworks, moderate graphitization, high specific surface area, good mesoporosity, and appropriate N doping. The CNCs-800 show high specific capacitance (248 F g(-1) at 1.0 A g(-1)), excellent rate capability (88% and 76% capacitance retention at 10 and 100 A g(-1), respectively), and outstanding cycling stability (~95% capacitance retention after 5000 cycles) in 6 M KOH aqueous solution. The CNCs-800 can also exhibit great pseudocapacitance in 0.5 M H2SO4 aqueous solution besides the large electrochemical double-layer capacitance. The excellent capacitance performance coupled with the facile synthesis of ultrathin nitrogen-doped graphitic CNCs indicates their great application potential in supercapacitors.

Enantioselective synthesis of cis-decalins using organocatalysis and sulfonyl Nazarov reagents.

PubMed

Peña, Javier; Silveira-Dorta, Gastón; Moro, Rosalina F; Garrido, Narciso M; Marcos, Isidro S; Sanz, Francisca; Díez, David

2015-04-10

The first organocatalytic synthesis of cis-decalins using sulfonyl Nazarov reagents is reported. The Jørgensen's catalyst directs this highly enantioselective synthesis using different cyclohexenal derivatives.

High-Throughput Synthesis and Structure of Zeolite ZSM-43 with Two-Directional 8-Ring Channels.

PubMed

Willhammar, Tom; Su, Jie; Yun, Yifeng; Zou, Xiaodong; Afeworki, Mobae; Weston, Simon C; Vroman, Hilda B; Lonergan, William W; Strohmaier, Karl G

2017-08-07

The aluminosilicate zeolite ZSM-43 (where ZSM = Zeolite Socony Mobil) was first synthesized more than 3 decades ago, but its chemical structure remained unsolved because of its poor crystallinity and small crystal size. Here we present optimization of the ZSM-43 synthesis using a high-throughput approach and subsequent structure determination by the combination of electron crystallographic methods and powder X-ray diffraction. The synthesis required the use of a combination of both inorganic (Cs + and K + ) and organic (choline) structure-directing agents. High-throughput synthesis enabled a screening of the synthesis conditions, which made it possible to optimize the synthesis, despite its complexity, in order to obtain a material with significantly improved crystallinity. When both rotation electron diffraction and high-resolution transmission electron microscopy imaging techniques are applied, the structure of ZSM-43 could be determined. The structure of ZSM-43 is a new zeolite framework type and possesses a unique two-dimensional channel system limited by 8-ring channels. ZSM-43 is stable upon calcination, and sorption measurements show that the material is suitable for adsorption of carbon dioxide as well as methane.

Combustion synthesis of ceramic-metal composite materials in microgravity

NASA Technical Reports Server (NTRS)

Moore, John

1995-01-01

Combustion synthesis, self-propagating high temperature synthesis (SHS) or reactive synthesis provides an attractive alternative to conventional methods of producing advanced materials since this technology is based on the ability of highly exothermic reactions to be self sustaining and, therefore, energetically efficient. The exothermic SHS reaction is initiated at the ignition temperature, T(sub ig), and generates heat which is manifested in a maximum or combustion temperature, T(sub c), which can exceed 3000 K . Such high combustion temperatures are capable of melting and/or volatilizing reactant and product species and, therefore, present an opportunity for producing structure and property modification and control through liquid-solid, vapor-liquid-solid, and vapor-solid transformations.

Synthesis of high luminescent carbon nanoparticles

NASA Astrophysics Data System (ADS)

Gvozdyuk, Alina A.; Petrova, Polina S.; Goryacheva, Irina Y.; Sukhorukov, Gleb B.

2017-03-01

In this article we report an effective and simple method for synthesis of high luminescent carbon nanodots (CDs). In our work as a carbon source sodium dextran sulfate (DS) was used because it is harmless, its analogs are used in medicine as antithrombotic compounds and blood substitutes after hemorrhage. was used as a substrate We investigated the influence of temperature parameters of hydrothermal synthesis on the photoluminescence (PL) intensity and position of emission maxima. We discovered that the PL intensity can be tuned by changing of synthesis temperature and CD concentration.

NWR (National Weather Service) voice synthesis project, phase 1

NASA Astrophysics Data System (ADS)

Sampson, G. W.

1986-01-01

The purpose of the NOAA Weather Radio (NWR) Voice Synthesis Project is to provide a demonstration of the current voice synthesis technology. Phase 1 of this project is presented, providing a complete automation of an hourly surface aviation observation for broadcast over NWR. In examining the products currently available on the market, the decision was made that synthetic voice technology does not have the high quality speech required for broadcast over the NWR. Therefore the system presented uses the phrase concatenation type of technology for a very high quality, versatile, voice synthesis system.

Water-Assisted Highly Efficient Synthesis of Impurity-Free Single-Walled Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Hata, Kenji; Futaba, Don N.; Mizuno, Kohei; Namai, Tatsunori; Yumura, Motoo; Iijima, Sumio

2004-11-01

We demonstrate the efficient chemical vapor deposition synthesis of single-walled carbon nanotubes where the activity and lifetime of the catalysts are enhanced by water. Water-stimulated enhanced catalytic activity results in massive growth of superdense and vertically aligned nanotube forests with heights up to 2.5 millimeters that can be easily separated from the catalysts, providing nanotube material with carbon purity above 99.98%. Moreover, patterned, highly organized intrinsic nanotube structures were successfully fabricated. The water-assisted synthesis method addresses many critical problems that currently plague carbon nanotube synthesis.

Direct and continuous synthesis of VO2 nanoparticles

NASA Astrophysics Data System (ADS)

Powell, M. J.; Marchand, P.; Denis, C. J.; Bear, J. C.; Darr, J. A.; Parkin, I. P.

2015-11-01

Monoclinic VO2 nanoparticles are of interest due to the material's thermochromic properties, however, direct synthesis routes to VO2 nanoparticles are often inaccessible due to the high synthesis temperatures or long reaction times required. Herein, we present a two-step synthesis route for the preparation of monoclinic VO2 nanoparticles using Continuous Hydrothermal Flow Synthesis (CHFS) followed by a short post heat treatment step. A range of particle sizes, dependent on synthesis conditions, were produced from 50 to 200 nm by varying reaction temperatures and the residence times in the process. The nanoparticles were characterised by powder X-ray diffraction, Raman and UV/Vis spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The nanoparticles were highly crystalline with rod and sphere-like morphologies present in TEM micrographs, with the size of both the rod and spherical particles being highly dependent on both reaction temperature and residence time. SEM micrographs showed the surface of the powders produced from the CHFS process to be highly uniform. The samples were given a short post synthesis heat treatment to ensure that they were phase pure monoclinic VO2, which led to them exhibiting a large and reversible switch in optical properties (at near-IR wavelengths), which suggests that if such materials can be incorporated into coatings or in composites, they could be used for fenestration in architectural applications.

Direct and continuous synthesis of VO2 nanoparticles.

PubMed

Powell, M J; Marchand, P; Denis, C J; Bear, J C; Darr, J A; Parkin, I P

2015-11-28

Monoclinic VO2 nanoparticles are of interest due to the material's thermochromic properties, however, direct synthesis routes to VO2 nanoparticles are often inaccessible due to the high synthesis temperatures or long reaction times required. Herein, we present a two-step synthesis route for the preparation of monoclinic VO2 nanoparticles using Continuous Hydrothermal Flow Synthesis (CHFS) followed by a short post heat treatment step. A range of particle sizes, dependent on synthesis conditions, were produced from 50 to 200 nm by varying reaction temperatures and the residence times in the process. The nanoparticles were characterised by powder X-ray diffraction, Raman and UV/Vis spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The nanoparticles were highly crystalline with rod and sphere-like morphologies present in TEM micrographs, with the size of both the rod and spherical particles being highly dependent on both reaction temperature and residence time. SEM micrographs showed the surface of the powders produced from the CHFS process to be highly uniform. The samples were given a short post synthesis heat treatment to ensure that they were phase pure monoclinic VO2, which led to them exhibiting a large and reversible switch in optical properties (at near-IR wavelengths), which suggests that if such materials can be incorporated into coatings or in composites, they could be used for fenestration in architectural applications.

Microflow High-p,T Intensification of Vitamin D3 Synthesis Using an Ultraviolet Lamp

PubMed Central

2017-01-01

Herewith a new process concept for synthesis is presented which combines both UV-photoirradiation and high-p,T intensification (photo-high-p,T) in continuous flow. The application of this procedure to Vitamin D3 synthesis promotes thermal shifting of the equilibrium from the reaction intermediate to the product. This is enabled by microreactors which allow operation under harsh conditions such as the high temperature used here. This provides, to our best knowledge, a new kind of process combination (novel process window). As a result, in less than 1 min, 42% conversion of 7-dehydrocholesterol can be achieved giving a 17% yield and 40% selectivity of Vitamin D3. This approach enhances productivity by up to 2 orders of magnitude compared with the current capillary based vitamin D3 synthesis, because, under the microflow conditions, photochemistry can be performed at fairly high concentration and up to 20 times faster. PMID:29503521

Sodium hydroxide catalyzed monodispersed high surface area silica nanoparticles.

PubMed

Bhakta, Snehasis; Dixit, Chandra K; Bist, Itti; Jalil, Karim Abdel; Suib, Steven L; Rusling, James F

2016-07-01

Understanding of the synthesis kinetics and our ability to modulate medium conditions allowed us to generate nanoparticles via an ultra-fast process. The synthesis medium is kept quite simple with tetraethyl orthosilicate (TEOS) as precursor and 50% ethanol and sodium hydroxide catalyst. Synthesis is performed under gentle conditions at 20 °C for 20 min Long synthesis time and catalyst-associated drawbacks are most crucial in silica nanoparticle synthesis. We have addressed both these bottlenecks by replacing the conventional Stober catalyst, ammonium hydroxide, with sodium hydroxide. We have reduced the overall synthesis time from 20 to 1/3 h, ~60-fold decrease, and obtained highly monodispersed nanoparticles with 5-fold higher surface area than Stober particles. We have demonstrated that the developed NPs with ~3-fold higher silane can be used as efficient probes for biosensor applications.

Plasma-assisted synthesis of MoS2

NASA Astrophysics Data System (ADS)

Campbell, Philip M.; Perini, Christopher J.; Chiu, Johannes; Gupta, Atul; Ray, Hunter S.; Chen, Hang; Wenzel, Kevin; Snyder, Eric; Wagner, Brent K.; Ready, Jud; Vogel, Eric M.

2018-03-01

There has been significant interest in transition metal dichalcogenides (TMDs), including MoS2, in recent years due to their potential application in novel electronic and optical devices. While synthesis methods have been developed for large-area films of MoS2, many of these techniques require synthesis temperatures of 800 °C or higher. As a result of the thermal budget, direct synthesis requiring high temperatures is incompatible with many integrated circuit processes as well as flexible substrates. This work explores several methods of plasma-assisted synthesis of MoS2 as a way to lower the synthesis temperature. The first approach used is conversion of a naturally oxidized molybdenum thin film to MoS2 using H2S plasma. Conversion is demonstrated at temperatures as low as 400 °C, and the conversion is enabled by hydrogen radicals which reduce the oxidized molybdenum films. The second method is a vapor phase reaction incorporating thermally evaporated MoO3 exposed to a direct H2S plasma, similar to chemical vapor deposition (CVD) synthesis of MoS2. Synthesis at 400 °C results in formation of super-stoichiometric MoS2 in a beam-interrupted growth process. A final growth method relies on a cyclical process in which a small amount of Mo is sputtered onto the substrate and is subsequently sulfurized in a H2S plasma. Similar results could be realized using an atomic layer deposition (ALD) process to deposit the Mo film. Compared to high temperature synthesis methods, the lower temperature samples are lower quality, potentially due to poor crystallinity or higher defect density in the films. Temperature-dependent conductivity measurements are consistent with hopping conduction in the plasma-assisted synthetic MoS2, suggesting a high degree of disorder in the low-temperature films. Optimization of the plasma-assisted synthesis process for slower growth rate and better stoichiometry is expected to lead to high quality films at low growth temperature.

The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure.

PubMed

Jortikka, M O; Parkkinen, J J; Inkinen, R I; Kärner, J; Järveläinen, H T; Nelimarkka, L O; Tammi, M I; Lammi, M J

2000-02-15

Chondrocytes of the articular cartilage sense mechanical factors associated with joint loading, such as hydrostatic pressure, and maintain the homeostasis of the extracellular matrix by regulating the metabolism of proteoglycans (PGs) and collagens. Intermittent hydrostatic pressure stimulates, while continuous high hydrostatic pressure inhibits, the biosynthesis of PGs. High continuous hydrostatic pressure also changes the structure of cytoskeleton and Golgi complex in cultured chondrocytes. Using microtubule (MT)-affecting drugs nocodazole and taxol as tools we examined whether MTs are involved in the regulation of PG synthesis in pressurized primary chondrocyte monolayer cultures. Disruption of the microtubular array by nocodazole inhibited [(35)S]sulfate incorporation by 39-48%, while MT stabilization by taxol caused maximally a 17% inhibition. Continuous hydrostatic pressure further decreased the synthesis by 34-42% in nocodazole-treated cultures. This suggests that high pressure exerts its inhibitory effect through mechanisms independent of MTs. On the other hand, nocodazole and taxol both prevented the stimulation of PG synthesis by cyclic 0. 5 Hz, 5 MPa hydrostatic pressure. The drugs did not affect the structural and functional properties of the PGs, and none of the treatments significantly affected cell viability, as indicated by the high level of PG synthesis 24-48 h after the release of drugs and/or high hydrostatic pressure. Our data on two-dimensional chondrocyte cultures indicate that inhibition of PG synthesis by continuous high hydrostatic pressure does not interfere with the MT-dependent vesicle traffic, while the stimulation of synthesis by cyclic pressure does not occur if the dynamic nature of MTs is disturbed by nocodazole. Similar phenomena may operate in cartilage matrix embedded chondrocytes. Copyright 2000 Academic Press.

A simple, rapid, high-fidelity and cost-effective PCR-based two-step DNA synthesis method for long gene sequences.

PubMed

Xiong, Ai-Sheng; Yao, Quan-Hong; Peng, Ri-He; Li, Xian; Fan, Hui-Qin; Cheng, Zong-Ming; Li, Yi

2004-07-07

Chemical synthesis of DNA sequences provides a powerful tool for modifying genes and for studying gene function, structure and expression. Here, we report a simple, high-fidelity and cost-effective PCR-based two-step DNA synthesis (PTDS) method for synthesis of long segments of DNA. The method involves two steps. (i) Synthesis of individual fragments of the DNA of interest: ten to twelve 60mer oligonucleotides with 20 bp overlap are mixed and a PCR reaction is carried out with high-fidelity DNA polymerase Pfu to produce DNA fragments that are approximately 500 bp in length. (ii) Synthesis of the entire sequence of the DNA of interest: five to ten PCR products from the first step are combined and used as the template for a second PCR reaction using high-fidelity DNA polymerase pyrobest, with the two outermost oligonucleotides as primers. Compared with the previously published methods, the PTDS method is rapid (5-7 days) and suitable for synthesizing long segments of DNA (5-6 kb) with high G + C contents, repetitive sequences or complex secondary structures. Thus, the PTDS method provides an alternative tool for synthesizing and assembling long genes with complex structures. Using the newly developed PTDS method, we have successfully obtained several genes of interest with sizes ranging from 1.0 to 5.4 kb.

Recent Advances in the Synthesis of High Explosive Materials

DTIC Science & Technology

2015-12-29

explosives and secondary high explosives, and the sensitivities and properties of these molecules are provided. In addition to the synthesis of such materials...This review discusses the recent advances in the syntheses of high explosive energetic materials. Syntheses of some relevant modern primary

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.

Micelle-template synthesis of nitrogen-doped mesoporous graphene as an efficient metal-free electrocatalyst for hydrogen production.

PubMed

Huang, Xiaodan; Zhao, Yufei; Ao, Zhimin; Wang, Guoxiu

2014-12-19

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.

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

GAP Peptide Synthesis via Design of New GAP Protecting Group: An Fmoc/tBu Synthesis of Thymopentin Free from Polymers, Chromatography and Recrystallization

PubMed Central

Seifert, Cole W.; Paniagua, Armando; White, Gabrielle A.; Cai, Lucy

2016-01-01

A novel method for Fmoc/tBu solution-phase peptide synthesis and the development of a new benzyl-type GAP protecting group is reported. This new GAP protecting group is utilized in place of a polymer support, facilitating C→N Fmoc peptide synthesis without chromatography, recrystallization, or polymer supports. The GAP group can be added and removed in high yield, and was used to synthesize over 1 gram of the immunostimulant, thymopentin, in high overall yield (83%) and purity (99%). PMID:28663711

Microgravity Production of Nanoparticles of Novel Materials Using Plasma Synthesis

NASA Technical Reports Server (NTRS)

Frenklach, Michael; Fernandez-Pello, Carlos

2001-01-01

The research goal is to study the formation in reduced gravity of high quality nanoparticulate of novel materials using plasma synthesis. Particular emphasis will be placed on the production of powders of non-oxide materials like diamond, SiC, SiN, c-BN, etc. The objective of the study is to investigate the effect of gravity on plasma synthesis of these materials, and to determine how the microgravity synthesis can improve the quality and yield of the nanoparticles. It is expected that the reduced gravity will aid in the understanding of the controlling mechanisms of plasma synthesis, and will increase the yield, and quality of the synthesized powder. These materials have properties of interest in several industrial applications, such as high temperature load bearings or high speed metal machining. Furthermore, because of the nano-meter size of the particulate produced in this process, they have specific application in the fabrication of MEMS based combustion systems, and in the development and growth of nano-systems and nano-structures of these materials. These are rapidly advancing research areas, and there is a great need for high quality nanoparticles of different materials. One of the primary systems of interest in the project will be gas-phase synthesis of nanopowder of non-oxide materials.

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.

Influence of Soil Factors on the Stereoselective Fate of a Novel Chiral Insecticide, Paichongding, in Flooded Paddy Soils.

PubMed

Li, Juying; Huang, Tuo; Li, Lizong; Ding, Tengda; Zhu, Hong; Yang, Bo; Ye, Qingfu; Gan, Jay

2016-11-02

In this study, the fate of paichongding was investigated in three soils with contrasting soil properties. In general, low soil pH has the potential to retard the mineralization and promote the dissipation of paichongding and the formation of its primary transformation product and to accelerate the formation of bound residue. The dissipation of paichongding stereoisomers was very fast and diastereoselective. This selectivity was found only between diastereomers and not between enantiomers and was observed to be soil dependent. In the acidic soil, the enantiomers (5R,7R)- and (5S,7S)-paichongding were degraded more quickly than (5R,7S)- and (5S,7R)-paichongding, whereas a contrary trend was observed in the neutral soil, and such selectivity did not occur in the alkaline soil. The OM and clay contents also played important roles in the fate of paichongding. This effect of soil properties should be considered in risk assessment of chiral pesticides and their application in the field.

Chirality- and sequence-selective successive self-sorting via specific homo- and complementary-duplex formations

PubMed Central

Makiguchi, Wataru; Tanabe, Junki; Yamada, Hidekazu; Iida, Hiroki; Taura, Daisuke; Ousaka, Naoki; Yashima, Eiji

2015-01-01

Self-recognition and self-discrimination within complex mixtures are of fundamental importance in biological systems, which entirely rely on the preprogrammed monomer sequences and homochirality of biological macromolecules. Here we report artificial chirality- and sequence-selective successive self-sorting of chiral dimeric strands bearing carboxylic acid or amidine groups joined by chiral amide linkers with different sequences through homo- and complementary-duplex formations. A mixture of carboxylic acid dimers linked by racemic-1,2-cyclohexane bis-amides with different amide sequences (NHCO or CONH) self-associate to form homoduplexes in a completely sequence-selective way, the structures of which are different from each other depending on the linker amide sequences. The further addition of an enantiopure amide-linked amidine dimer to a mixture of the racemic carboxylic acid dimers resulted in the formation of a single optically pure complementary duplex with a 100% diastereoselectivity and complete sequence specificity stabilized by the amidinium–carboxylate salt bridges, leading to the perfect chirality- and sequence-selective duplex formation. PMID:26051291

Development and Comparison of the Substrate Scope of Pd-Catalysts for the Aerobic Oxidation of Alcohols

PubMed Central

Schultz, Mitchell J.; Hamilton, Steven S.; Jensen, David R.; Sigman, Matthew S.

2009-01-01

Three catalysts for aerobic oxidation of alcohols are discussed and the effectiveness of each is evaluated for allylic, benzylic, aliphatic, and functionalized alcohols. Additionally, chiral nonracemic substrates as well as chemoselective and diastereoselective oxidations are investigated. In this study, the most convenient system for the Pd-catalyzed aerobic oxidation of alcohols is Pd(OAc)2 in combination with triethylamine. This system functions effectively for the majority of alcohols tested and uses mild conditions (3 to 5 mol % of catalyst, room temperature). Pd(IiPr)(OAc)2(H2O) (1) also successfully oxidizes the majority of alcohols evaluated. This system has the advantage of significantly lowering catalyst loadings but requires higher temperatures (0.1 to 1 mol % of catalyst, 60 °C). A new catalyst is also disclosed, Pd(IiPr)(OPiv)2 (2). This catalyst operates under very mild conditions (1 mol %, room temperature, and air as the O2 source) but with a more limited substrate scope. PMID:15844968

The Experimental Evidence in Support of Glycosylation Mechanisms at the SN1-SN2 Interface.

PubMed

Adero, Philip Ouma; Amarasekara, Harsha; Wen, Peng; Bohé, Luis; Crich, David

2018-05-30

A critical review of the state-of-the-art evidence in support of the mechanisms of glycosylation reactions is provided. Factors affecting the stability of putative oxocarbenium ions as intermediates at the S N 1 end of the mechanistic continuum are first surveyed before the evidence, spectroscopic and indirect, for the existence of such species on the time scale of glycosylation reactions is presented. Current models for diastereoselectivity in nucleophilic attack on oxocarbenium ions are then described. Evidence in support of the intermediacy of activated covalent glycosyl donors is reviewed, before the influences of the structure of the nucleophile, of the solvent, of temperature, and of donor-acceptor hydrogen bonding on the mechanism of glycosylation reactions are surveyed. Studies on the kinetics of glycosylation reactions and the use of kinetic isotope effects for the determination of transition-state structure are presented, before computational models are finally surveyed. The review concludes with a critical appraisal of the state of the art.

Conceptual study of an optical aperture synthesis system for high resolution astronomy

NASA Astrophysics Data System (ADS)

Calvel, Bertrand

2018-04-01

This paper, "Conceptual study of an optical aperture synthesis system for high resolution astronomy," was presented as part of International Conference on Space Optics—ICSO 1997, held in Toulouse, France.

DECOUPLING OF PROTEIN AND RNA SYNTHESIS DURING DEUTERIUM PARTHENOGENESIS IN SEA URCHIN EGGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross, P.R.; Spindel, W.; Cousineau, G.H.

1963-10-29

The parthenogenetic activation of cell division and suppression of nucleic acid synthesis by deuterium in eggs of sea urchins was investigated. D/ sub 2/O treatment was found to evoke a high rate of protein synthesis in the eggs that was maintained for several hours. However, eggs whose protein synthesis was activated and that were making labeled cytasters showed no increment in RNA synthesis over controls. (P.C.H.)

Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process

PubMed Central

LeProust, Emily M.; Peck, Bill J.; Spirin, Konstantin; McCuen, Heather Brummel; Moore, Bridget; Namsaraev, Eugeni; Caruthers, Marvin H.

2010-01-01

We have achieved the ability to synthesize thousands of unique, long oligonucleotides (150mers) in fmol amounts using parallel synthesis of DNA on microarrays. The sequence accuracy of the oligonucleotides in such large-scale syntheses has been limited by the yields and side reactions of the DNA synthesis process used. While there has been significant demand for libraries of long oligos (150mer and more), the yields in conventional DNA synthesis and the associated side reactions have previously limited the availability of oligonucleotide pools to lengths <100 nt. Using novel array based depurination assays, we show that the depurination side reaction is the limiting factor for the synthesis of libraries of long oligonucleotides on Agilent Technologies’ SurePrint® DNA microarray platform. We also demonstrate how depurination can be controlled and reduced by a novel detritylation process to enable the synthesis of high quality, long (150mer) oligonucleotide libraries and we report the characterization of synthesis efficiency for such libraries. Oligonucleotide libraries prepared with this method have changed the economics and availability of several existing applications (e.g. targeted resequencing, preparation of shRNA libraries, site-directed mutagenesis), and have the potential to enable even more novel applications (e.g. high-complexity synthetic biology). PMID:20308161

A Comparison of Wavetable and FM Data Reduction Methods for Resynthesis of Musical Sounds

NASA Astrophysics Data System (ADS)

Horner, Andrew

An ideal music-synthesis technique provides both high-level spectral control and efficient computation. Simple playback of recorded samples lacks spectral control, while additive sine-wave synthesis is inefficient. Wavetable and frequencymodulation synthesis, however, are two popular synthesis techniques that are very efficient and use only a few control parameters.

Trends in high pressure developments for new perspectives

NASA Astrophysics Data System (ADS)

Largeteau, Alain; Prakasam, Mythili

2018-06-01

Temperature and Pressure are two parameters in the universe, where pressure represents the largest scale in comparison to temperature. The design of high pressure equipment depends mainly on the media used which could be gas, liquid or solid and the objective could be synthesis of materials or in situ characterization. The development of new research fields requiring high pressure equipment which are currently in Bordeaux - France are based on the historical development of high pressure domain initiated by Professor Gerard DEMAZEAU and his team during the last half century, which is discussed here. The main concepts governing the effect of pressure on materials synthesis is by the combination of high pressure and high temperature which are described with apt examples. There is an upsurge in various technologies for strong development for the synthesis of materials to drive several possibilities, for example: to reach very high density to obtain optical ceramics (by conventional SPS), to diminish parameters (P, T, t) of synthesis (by HP-SPS), to sinter at low temperature thermal sensitive composition (by HyS), to consolidate porous materials (by FIP), to densify biocomposite with cold decontamination (by HHP) simultaneously, etc.

Elucidating the reaction pathways in the synthesis of organolead trihalide perovskite for high-performance solar cells.

PubMed

Wang, Baohua; Young Wong, King; Xiao, Xudong; Chen, Tao

2015-05-28

The past two years have witnessed unprecedentedly rapid development of organic-inorganic halide perovskite-based solar cells. The solution-processability and high efficiency make this technology extraordinarily attractive. The intensive investigations have accumulated rich experiences in the perovskite fabrication; while the mechanism of the chemical synthesis still remains unresolved. Here, we set up the chemical equation of the synthesis and elucidate the reactions from both thermodynamic and kinetic perspectives. Our study shows that gaseous products thermodynamically favour the reaction, while the activation energy and "collision" probability synergistically determine the reaction rate. These understandings enable us to finely tune the crystal size for high-quality perovskite film, leading to a record fill factor among similar device structures in the literature. This investigation provides a general strategy to explore the mechanism of perovskite synthesis and benefits the fabrication of high-efficiency perovskite photoactive layer.

Fast and inexpensive synthesis of pentacene with high yield using 6,13-pentacenequinone as precursor

NASA Astrophysics Data System (ADS)

Mota, María L.; Rodriguez, Bibiana; Carrillo, Amanda; Ambrosio, Roberto C.; Luque, Priscy A.; Mireles, Marcela; Vivaldo, Israel; Quevedo, Manuel A.

2018-02-01

Pentacene is an important semiconductor in the field of organic electronics. In this work is presented an alternative synthesis procedure to obtain pentacene from 6,13-pentacenequinone as a precursor. Synthesis of pentacene was performed in two reactions, Diels-Adler cycloaddition of 6,13-pentacenequinone followed by 6,13-pentacenequinone reduction to pentacene, employing LiAlH4 as reducing agent. The products were characterized by Fourier Transform Infrared Spectroscopy (FTIR), 1H-Nuclear Magnetic Resonance Spectroscopy (1H-NMR), X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA) and Ultraviolet-Visible Spectroscopy (UV-VIS). In this work, 6,13-pentacenequinone was synthetized with a high yield (55%) using an alternative method. The optimization process resulted in an overall reduction of reaction time while exhibiting high yield. The method presented here provides an affordable pentacene synthesis route with high purity, which can be further applied for research and development of organic electronic applications.

In-site synthesis of monodisperse, oleylamine-capped Ag nanoparticles through microemulsion approach

NASA Astrophysics Data System (ADS)

Chen, Shun; Ju, Yanyun; Guo, Yi; Xiong, Chuanxi; Dong, Lijie

2017-03-01

Ag NPs were in-site synthesized through microemulsion method by reducing silver acetate with oleylamine-mediated at 70 °C with highly monodisperse and narrow size from 10 to 20 nm. The synthesis of Ag NPs was aided by oleylamine and the role of oleylamine was researched. This in-site synthesis approach to Ag NPs was reproducibility and high yield more than 80% with stable store about 6 months.

Convenient divergent strategy for the synthesis of TunePhos-type chiral diphosphine ligands and their applications in highly enantioselective Ru-catalyzed hydrogenations.

PubMed

Sun, Xianfeng; Zhou, Le; Li, Wei; Zhang, Xumu

2008-02-01

A convenient, divergent strategy for the synthesis of a series of modular and fine-tunable C3-TunePhos-type chiral diphosphine ligands and their applications in highly efficient Ru-catalyzed asymmetric hydrogenations were explored. Up to 97 and 99% ee values were achieved for the enantioselective synthesis of beta-methyl chiral amines and alpha-hydroxy acid derivatives, respectively.

Total Synthesis of Tiacumicin A. Total Synthesis, Relay Synthesis, and Degradation Studies of Fidaxomicin (Tiacumicin B, Lipiarmycin A3).

PubMed

Hattori, Hiromu; Kaufmann, Elias; Miyatake-Ondozabal, Hideki; Berg, Regina; Gademann, Karl

2018-04-12

The commercial macrolide antibiotic fidaxomicin was synthesized in a highly convergent manner. Salient features of this synthesis include a β-selective noviosylation, a β-selective rhamnosylation, a ring-closing metathesis, a Suzuki coupling, and a vinylogous Mukaiyama aldol reaction. Careful choice of protecting groups and fine-tuning of the glycosylation reactions led to the first total synthesis of fidaxomicin. In addition, a relay synthesis of fidaxomicin was established, which gives access to a conveniently protected intermediate from the natural material for derivatization. The first total synthesis of a related congener, tiacumicin A, is presented.

A totally phosphine-free synthesis of metal telluride nanocrystals by employing alkylamides to replace alkylphosphines for preparing highly reactive tellurium precursors.

PubMed

Yao, Dong; Liu, Yi; Zhao, Wujun; Wei, Haotong; Luo, Xintao; Wu, Zhennan; Dong, Chunwei; Zhang, Hao; Yang, Bai

2013-10-21

Despite the developments in the wet chemical synthesis of high-quality semiconductor nanocrystals (NCs) with diverse elemental compositions, telluride NCs are still irreplaceable materials owing to their excellent photovoltaic and thermoelectric performances. Herein we demonstrate the dissolution of elemental tellurium (Te) in a series of alkylamides by sodium borohydride (NaBH4) reduction at relatively low temperature to produce highly reactive precursors for hot-injection synthesis of telluride NCs. The capability to tune the reactivity of Te precursors by selecting injection temperature permits control of NC size over a broad range. The current preparation of Te precursors is simple, economical, and totally phosphine-free, which will promote the commercial synthesis and applications of telluride NCs.

The effect of adding CTAB template in ZSM-5 synthesis

NASA Astrophysics Data System (ADS)

Widayat, Widayat; Annisa, Arianti Nuur

2017-11-01

In general, ZSM-5 synthesis is performed using a hydrothermal process that takes place at high temperature and high pressure (> 373 K,> 1 bar). The synthesis of ZSM-5 is influenced by the organic template used. The organic template serves as a determinant of the zeolite crystal structure formation. CTAB is an easily found organic template and the price is cheap so the production cost of ZSM-5 synthesis would be more efficient. In this research, ZSM-5 is synthesized by varying temperature and crystallization time. The result showed the optimal condition of ZSM-5 synthesis was at 363 K for the crystallization temperature with 8 hours of crystallization time. The crystalline product had 60.07% of crystallinity with an aluminosilicate composition of 72% w/w.

Assessment of protein synthesis in highly aerobic canine species at the onset and during exercise training.

PubMed

Miller, Benjamin F; Ehrlicher, Sarah E; Drake, Joshua C; Peelor, Frederick F; Biela, Laurie M; Pratt-Phillips, Shannon; Davis, Michael; Hamilton, Karyn L

2015-04-01

Canis lupus familiaris, the domesticated dog, is capable of extreme endurance performance. The ability to perform sustained aerobic exercise is dependent on a well-developed mitochondrial reticulum. In this study we examined the cumulative muscle protein and DNA synthesis in groups of athletic dogs at the onset of an exercise training program and following a strenuous exercise training program. We hypothesized that both at the onset and during an exercise training program there would be greater mitochondrial protein synthesis rates compared with sedentary control with no difference in mixed or cytoplasmic protein synthesis rates. Protein synthetic rates of three protein fractions and DNA synthesis were determined over 1 wk using (2)H2O in competitive Alaskan Huskies and Labrador Retrievers trained for explosive device detection. Both groups of dogs had very high rates of skeletal muscle protein synthesis in the sedentary state [Alaskan Huskies: Mixed = 2.28 ± 0.12, cytoplasmic (Cyto) = 2.91 ± 0.10, and mitochondrial (Mito) = 2.62 ± 0.07; Labrador Retrievers: Mixed = 3.88 ± 0.37, Cyto = 3.85 ± 0.06, and Mito = 2.92 ± 0.20%/day]. Mitochondrial (Mito) protein synthesis rates did not increase at the onset of an exercise training program. Exercise-trained dogs maintained Mito protein synthesis during exercise training when mixed (Mixed) and cytosolic (Cyto) fractions decreased, and this coincided with a decrease in p-RpS6 but also a decrease in p-ACC signaling. Contrary to our hypothesis, canines did not have large increases in mitochondrial protein synthesis at the onset or during an exercise training program. However, dogs have a high rate of protein synthesis compared with humans that perhaps does not necessitate an extra increase in protein synthesis at the onset of aerobic exercise training. Copyright © 2015 the American Physiological Society.

Finite element design for the HPHT synthesis of diamond

NASA Astrophysics Data System (ADS)

Li, Rui; Ding, Mingming; Shi, Tongfei

2018-06-01

The finite element method is used to simulate the steady-state temperature field in diamond synthesis cell. The 2D and 3D models of the China-type cubic press with large deformation of the synthesis cell was established successfully, which has been verified by situ measurements of synthesis cell. The assembly design, component design and process design for the HPHT synthesis of diamond based on the finite element simulation were presented one by one. The temperature field in a high-pressure synthetic cavity for diamond production is optimized by adjusting the cavity assembly. A series of analysis about the influence of the pressure media parameters on the temperature field are examined through adjusting the model parameters. Furthermore, the formation mechanism of wasteland was studied in detail. It indicates that the wasteland is inevitably exists in the synthesis sample, the distribution of growth region of the diamond with hex-octahedral is move to the center of the synthesis sample from near the heater as the power increasing, and the growth conditions of high quality diamond is locating at the center of the synthesis sample. These works can offer suggestion and advice to the development and optimization of a diamond production process.

Synthesis of potassium ferrate using residual ferrous sulfate as iron bearing material

NASA Astrophysics Data System (ADS)

Kanari, N.; Filippov, L.; Diot, F.; Mochón, J.; Ruiz-Bustinza, I.; Allain, E.; Yvon, J.

2013-03-01

This paper summarizes the results obtained during potassium ferrate (K2FeVIO4) synthesis which is a high added value material. This compound that contains iron in the rare hexavalent state is becoming a substance of growing importance for the water and effluent treatment industries. This is due to its multi-functional nature (oxidation, flocculation, elimination of heavy metals, decomposition of organic matter, etc.). The most well known synthesis methods for potassium ferrate synthesis are those involving the chemical and/or electrochemical oxidation of iron (II) and (III) from aqueous solutions having a high alkali concentration. These methods are generally characterized by a low FeVI efficiency due to the reaction of the potassium ferrate with water, leading to the reduction of FeVI into FeIII. Concerning the work pertinent to this paper, the synthesis of K2FeVIO4 was achieved by a simultaneous reaction of two solids (iron sulfate and KOH) and one gaseous oxidant (chlorine). The synthesis process is performed in a rotary reactor at room temperature and the global synthesis reaction is exothermic. The effects of different experimental parameters on the potassium ferrate synthesis are investigated to determine the optimal conditions for the process.

High-pressure synthesis of mesoporous stishovite: potential applications in mineral physics

NASA Astrophysics Data System (ADS)

Stagno, Vincenzo; Mandal, Manik; Landskron, Kai; Fei, Yingwei

2015-06-01

Recently, we have described a successful synthesis route to obtain mesoporous quartz and its high-pressure polymorph coesite by nanocasting at high pressure using periodic mesostructured precursors, such as SBA-16 and FDU-12/carbon composite as starting materials. Periodic mesoporous high-pressure silica polymorphs are of particular interest as they combine transport properties and physical properties such as hardness that potentially enable the industrial use of these materials. In addition, synthesis of mesoporous crystalline silica phases can allow more detailed geology-related studies such as water/mineral interaction, dissolution/crystallization rate and the surface contribution to the associated thermodynamic stability (free energy and enthalpy) of the various polymorphs and their crossover. Here, we present results of synthesis of mesoporous stishovite from cubic large-pore periodic mesoporous silica LP-FDU-12/C composite as precursor with an fcc lattice. We describe the synthesis procedure using multi-anvil apparatus at 9 GPa (about 90,000 atm) and temperature of 500 °C. The synthetic mesoporous stishovite is, then, characterized by wide and small-angle X-ray diffraction, scanning/transmission electron microscopy and gas adsorption. Results show that this new material is characterized by accessible mesopores with wide pore size distribution, surface area of ~45 m2/g and volume of pores of ~0.15 cm3/g. Results from gas adsorption indicate that both porosity and permeability are retained at the high pressures of synthesis but with weak periodic order of the pores.

Stereoselective synthesis of novel highly substituted isochromanone and isoquinolinone-containing exocyclic tetrasubstituted alkenes.

PubMed

Arthuis, Martin; Pontikis, Renée; Florent, Jean-Claude

2009-03-06

An efficient synthetic route toward the synthesis of highly substituted arylethylidene-isoquinolinones/isochromanones is reported. The tandem carbopalladation/Suzuki-Miyaura coupling sequence stereoselectively provided various functionalized polycyclic compounds in moderate to excellent yields.

SVS (Self-Propagating High-Temperature Synthesis)

NASA Image and Video Library

2009-08-21

ISS020-E-032798 (21 Aug. 2009) --- Cosmonaut Roman Romanenko, Expedition 20 flight engineer, works with video equipment and a Russian payload TkhN-7 Self-Propagating High-Temperature Synthesis in the Zvezda Service Module of the International Space Station.

Highly efficient water-mediated approach to access benzazoles: metal catalyst and base-free synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles.

PubMed

Bala, Manju; Verma, Praveen Kumar; Sharma, Deepika; Kumar, Neeraj; Singh, Bikram

2015-05-01

An efficient water-catalyzed method has been developed for the synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles in one step. The present method excludes the usage of toxic metal catalysts and bases to produce benzazoles in good to excellent yields. An efficient and versatile water-mediated method has been established for the synthesis of various 2-arylbenzazoles. The present protocol excludes the usage of any catalyst and additive provided excellent selectivities and yields with high functional group tolerance for the synthesis of 2-arylated benzimidazoles, benzoxazoles, and benzothiazoles. Benzazolones were also synthesized using similar reaction protocol.

Water-Assisted Highly Efficient Synthesis of Impurity-Free Single-Walled Carbon Nanotubes-``Super-Growth''

NASA Astrophysics Data System (ADS)

Hata, Kenji

2005-03-01

We demonstrate an extremely efficient chemical vapour deposition synthesis of single-walled carbon nanotubes where the activity and lifetime of the catalysts are enhanced by water [1]. Water-stimulated enhanced catalytic activity results in massive growth of super-dense and vertically-aligned nanotube forests with heights up to 2.5 millimeters that can be easily separated from the catalysts, providing nanotube material with carbon purity above 99.98%. Moreover, patterned highly organized intrinsic nanotube structures were successfully fabricated. The water-assisted synthesis method addresses many critical problems that currently plague carbon nanotube synthesis. [1] K. Hata, et al., Science, 306, 1362 (2004).

Rare Earth Ion-Doped Upconversion Nanocrystals: Synthesis and Surface Modification

PubMed Central

Chang, Hongjin; Xie, Juan; Zhao, Baozhou; Liu, Botong; Xu, Shuilin; Ren, Na; Xie, Xiaoji; Huang, Ling; Huang, Wei

2014-01-01

The unique luminescent properties exhibited by rare earth ion-doped upconversion nanocrystals (UCNPs), such as long lifetime, narrow emission line, high color purity, and high resistance to photobleaching, have made them widely used in many areas, including but not limited to high-resolution displays, new-generation information technology, optical communication, bioimaging, and therapy. However, the inherent upconversion luminescent properties of UCNPs are influenced by various parameters, including the size, shape, crystal structure, and chemical composition of the UCNPs, and even the chosen synthesis process and the surfactant molecules used. This review will provide a complete summary on the synthesis methods and the surface modification strategies of UCNPs reported so far. Firstly, we summarize the synthesis methodologies developed in the past decades, such as thermal decomposition, thermal coprecipitation, hydro/solvothermal, sol-gel, combustion, and microwave synthesis. In the second part, five main streams of surface modification strategies for converting hydrophobic UCNPs into hydrophilic ones are elaborated. Finally, we consider the likely directions of the future development and challenges of the synthesis and surface modification, such as the large-scale production and actual applications, stability, and so on, of the UCNPs. PMID:28346995

Synthesis and Biological Evaluation of Thiosemicarbazide Derivatives Endowed with High Activity toward Mycobacterium Bovis.

PubMed

Sardari, Soroush; Feizi, Samaneh; Rezayan, Ali Hossein; Azerang, Parisa; Shahcheragh, Seyyed Mohammad; Ghavami, Ghazaleh; Habibi, Azizollah

2017-01-01

Thiosemicarbazides are potent intermediates for the synthesis of pharmaceutical and bioactive materials and thus, they are used extensively in the field of medicinal chemistry. The imine bond (-N=CH-) in this compounds are useful in organic synthesis, in particular for the preparation of heterocycles and non-natural β-aminoacids. In this paper the synthesis of some new thiosemicarbazide derivatives by condensation reaction of various aldehydes or ketones with 4-phenylthiosemicarbazide or thiosemicarbazide is reported. This synthesis method has the advantages of high yields and good bioactivity. The structures of these compounds were confirmed by IR, mass, 1 H NMR, 13 C NMR, and single-crystal X-ray diffraction studies. All of these compounds were tested for their in-vitro anti-mycobacterial activity. The influence of the functional group and position of substituent on anti-bacterial activity of compounds is investigated too. The preliminary results indicated that all of the tested compounds showed good activity against the test organism. The compounds 11 and 30 showed the highest anti-tubercular activity (0.39 μg/mL). This synthesis method has the advantages of high yields and good bioactivity.

Rhodium mediated bond activation: from synthesis to catalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Hung-An

Recently, our lab has developed monoanionic tridentate ligand, To R, showing the corresponding coordination chemistry and catalyst reactivity of magnesium, zirconium, zinc and iridium complexes. This thesis details synthetic chemistry, structural study and catalytic reactivity of the To R-supported rhodium compounds. Tl[To R] has been proved to be a superior ligand transfer agent for synthesizing rhodium complexes. The salt metathesis route of Tl[To M] with [Rh(μ-Cl)(CO)] 2 and [Rh(μ- Cl)(COE)] 2 gives To MRh(CO) 2 (2.2) and To MRhH(β 3-C 8H 13) (3.1) respectively while Tl[To M] with [Rh(μ-Cl)(CO)] 2 affords To PRh(CO) 2 (2.3). 2.2 reacts with both strongmore » and weak electrophiles, resulting in the oxazoline N-attacked and the metal center-attacked compounds correspondingly. Using one of the metal center-attacked electrophiles, 2.3 was demonstrated to give high diastereoselectivity. Parallel to COE allylic C-H activation complex 3.1, the propene and allylbenzene allylic C-H activation products have also been synthesized. The subsequent functionalization attempts have been examined by treating with Brønsted acids, Lewis acids, electrophiles, nucleophiles, 1,3-dipolar reagents and reagents containing multiple bonds able to be inserted. Various related complexes have been obtained under these conditions, in which one of the azide insertion compounds reductively eliminates to give an allylic functionalization product stoichiometrically. 3.1 reacts with various primary alcohols to give the decarbonylation dihydride complex To MRh(H) 2CO (4.1). 4.1 shows catalytic reactivity for primary alcohol decarbonylation under a photolytic condition. Meanwhile, 2.2 has been found to be more reactive than 4.1 for catalytic alcohol decarbonylation under the same condition. Various complexes and primary alcohols have been investigated as well. The proposed mechanism is based on the stochiometric reactions of the possible metal and organic intermediates. Primary amines, hypothesized to undergo a similar reaction pathway, have been verified to give dehydrogenative coupling product, imines. In the end, the well-developed neutral tridentate Tpm coordinates to the rhodium bis(ethylene) dimer in the presence of TlPF 6 to give the cationic complex, [TpmRh(C 2H 4) 2][PF 6] (5.1). 5.1 serves as the first example of explicit determination of the solid state hapticity, evidenced by X-ray structure, among all the cationic Tpm RM(C 2H 4) 2 + (Tpm R = Tpm, Tpm*, M = Rh, Ir) derivatives. The substitution chemistry of this compound has been studied by treating with soft and hard donors. The trimethylphosphine-sbustituted complex activates molecular hydrogen to give the dihydride compound.« less

Control of synthesis and release of radioactive acetylcholine in brain slices from the rat. Effects of neurotropic drugs

PubMed Central

Grewaal, D. S.; Quastel, J. H.

1973-01-01

1. Studies of the synthesis and release of radioactive acetylcholine in rat brain-cortex slices incubated in Locke–bicarbonate–[U-14C]glucose media, containing paraoxon as cholinesterase inhibitor, revealed the following phenomena: (a) dependence of K+-or protoveratrine-stimulated acetylcholine synthesis and release on the presence of Na+ and Ca2+ in the incubation medium, (b) enhanced release of radioactive acetylcholine by substances that promote depolarization at the nerve cell membrane (e.g. high K+, ouabain, protoveratrine, sodium l-glutamate, high concentration of acetylcholine), (c) failure of acetylcholine synthesis to keep pace with acetylcholine release under certain conditions (e.g. the presence of ouabain or lack of Na+). 2. Stimulation by K+ of radioactive acetylcholine synthesis was directly proportional to the external concentration of Na+, but some synthesis and release of radioactive acetylcholine occurred in the absence of Na+ as well as in the absence of Ca2+. 3. The Na+ dependence of K+-stimulated acetylcholine synthesis was partly due to suppression of choline transport, as addition of small concentrations of choline partly neutralized the effect of Na+ lack, and partly due to the suppression of the activity of the Na+ pump. 4. Protoveratrine caused a greatly increased release of radioactive acetylcholine without stimulating total radioactive acetylcholine synthesis. Protoveratrine was ineffective in the absence of Ca2+ from the incubation medium. It completely blocked K+ stimulation of acetylcholine synthesis and release. 5. Tetrodotoxin abolished the effects of protoveratrine on acetylcholine release. It had blocking effects (partial or complete) on the action of high K+, sodium l-glutamate and lack of Ca2+ on acetylcholine synthesis and release. 6. Unlabelled exogenous acetylcholine did not diminish the content of labelled tissue acetylcholine, derived from labelled glucose, suggesting that no exchange with vesicular acetylcholine took place. In the presence of 4mm-KCl it caused some increase in the release of labelled acetylcholine. 7. The barbiturates (Amytal, pentothal), whilst having no significant effects on labelled acetylcholine synthesis in unstimulated brain except at high concentration (1mm), diminished or abolished (at 0.25 or 0.5mm) the enhanced release of acetylcholine, due to high K+ or lack of Ca2+. The fall in tissue content of acetylcholine, due to lack of Ca2+, was diminished or abolished by pentothal (0.25 or 0.5mm) or Amytal (0.25mm). PMID:4722896

New Synthesis Of High-Performance Bismaleimides

NASA Technical Reports Server (NTRS)

Pater, Ruth H.; Lowther, Sharon; Cannon, Michelle; Smith, Janice; Whitely, Karen

1991-01-01

New general synthesis of tough and easy-to-process high-performance bismaleimides (BMI's) developed. Involves reaction of acetylene-terminated compounds with BMI's or biscitraconimides. Offers matrix resins and adhesives having combined advantages of toughness characteristic of thermoplastics and easy processability characteristic of thermosetting materials. Scheme has potential for providing high-performance matrix resins surviving well at high temperatures and absorb little moisture.

Synthesis and Characterization of Polymers for Fuel Cells Application

NASA Technical Reports Server (NTRS)

Tytko, Stephen F.

2003-01-01

The goal of this summer research is to prepare Polymer Exchange Membranes (PEM s) for fuel cell application. Several high temperature polymers such as polybenzimidazoles and polyether ketones were known to possess good high temperature stability and had been investigated by post-sulfonation to yield sulfonated polymers. The research project will involve two approaches: 1. Synthesis of polybenzimidazoles and then react with alkyl sultonse to attach an aliphatic sulfonic groups. 2. Synthesis of monomers containing sulfonic acid units either on a aromatic ring or on an aliphatic chain and then polymerize the monomers to form high molecular weight sulfonate polymers.

Recent Advances in the Catalytic One-Pot Synthesis of Flavonoids and Chromones.

PubMed

Mohadeszadeh, Manijeh; Iranshahi, Mehrdad

2017-01-01

Flavonoids and chromones are two important classes of natural products that have various biological properties. During the past 10 years, there has been a significant increase in studies on the one-pot synthesis of flavonoids and chromones as medicinal scaffolds in drug discovery. This review describes the scope, mechanistic properties and regio- and chemo-selectivity features of several recently developed one-pot procedures for the synthesis of substituted chromones and flavonoids that have recently been published. Special importance is placed on the most promising and exciting medicinal applications of flavonoids and chromones. In this review, we discuss the progress on the synthesis of flavonoid and chromone derivatives in the presence of metal catalysts, organocatalysts, solid surfaces, microwave irradiation, acid and base catalysis, etc. For example, flavones can be prepared via the catalytic coordination of palladium complexes in a short time and at a low temperature with a high yield. Additionally, the one-pot synthesis of 2-substituted chromones via metal triflate (Yb(OTf)3) has provided the best result for this type of reaction with a high yield and a high regio and chemoselectivity. Generally, this review proposes the first specific overview of this developing and rapidly expanding field of flavonoid synthesis. We also discuss the mechanisms and advantages and disadvantages of methods for the synthesis of flavonoids and chromones. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Growth, oxygen consumption, and protein and RNA synthesis rates in the yolk sac larvae of the African catfish (Clarias gariepinus).

PubMed

Smith, Richard W; Ottema, Colin

2006-03-01

Rapidly growing African catfish yolk sac larvae were investigated during the first 22 h after hatching. Body compartment protein concentration increased fourfold yet oxygen consumption remained constant (mean=21.3 +/- 3.2 nmol O2 mg(-1) protein h(-1)), suggesting fast growth results mainly from yolk sac protein absorption. The protein synthesis rates at 1-2 and 5-6 h also equaled the highest conceivable rates of muscle protein synthesis; 11.6-11.9% and 7.4-7.9% day(-1), respectively. Therefore the corresponding energetic costs of protein synthesis were almost the theoretical minimum; 13.0 +/- 1.7-16.3 +/- 2.8 micromol O2 mg(-1) protein synthesised. Total protein synthesis expenditure (74.5-77.7 micromol O2 g(-1) protein h(-1)) was also less than other yolk sac larvae. These protein synthesis rates resulted from high RNA concentrations (113.2 +/- 3.4 microg RNA mg(-1) protein) and were also correlated with RNA translational efficiency. High translational efficiency (1 h; 1.2+/-0.1 mg protein synthesised microg(-1) RNA day(-1)) equaled high synthesis rate (36.8 +/- 5.4 microg RNA microg(-1) DNA day(-1)) and both declined over 22 h. This investigation suggests rapid growth combines growth efficiency and compensatory energy partitioning. This accommodates the ontogenetic and phylogenetic standpoints imposed by energy budget limitations.

Green synthesis and characterisation of platinum nanoparticles using quail egg yolk

NASA Astrophysics Data System (ADS)

Nadaroglu, Hayrunnisa; Gungor, Azize Alayli; Ince, Selvi; Babagil, Aynur

2017-02-01

Nanotechnology is extensively used in all parts today. Therefore, nano synthesis is also significant in all explored areas. The results of studies conducted have revealed that nanoparticle synthesis is performed by using both chemical and physical methods. It is well known that these syntheses are carried out at high charge, pressure and temperature in harsh environments. Therefore, this study investigated green synthesis method that sustains more mild conditions. In this study, quail egg yolk having high vitamin and protein content was prepared for green synthesis reaction and used for the synthesis of platinum nanoparticles in the reaction medium. Reaction situations were optimised as a function of pH, temperature, time and concentration by using quail egg yolk. The results showed that the highest platinum nanoparticles were synthesised at 20 °C and pH 6.0 for 4 h. Also, optimal concentration of metal ions was established as 0.5 mM. The synthesised platinum nanoparticles were characterised by using UV spectrum, X-ray diffraction and scanning electron microscope.

Synthesis of densely functionalized enantiopure indolizidines by ring-closing metathesis (RCM) of hydroxylamines from carbohydrate-derived nitrones

PubMed Central

Bonanni, Marco; Marradi, Marco; Cardona, Francesca; Cicchi, Stefano; Goti, Andrea

2007-01-01

Background Indolizidine alkaloids widely occur in nature and display interesting biological activity. This is the reason for which their total synthesis as well as the synthesis of non-natural analogues still attracts the attention of many research groups. To establish new straightforward accesses to these molecules is therefore highly desirable. Results The ring closing metathesis (RCM) of enantiopure hydroxylamines bearing suitable unsaturated groups cleanly afforded piperidine derivatives in good yields. Further cyclization and deprotection of the hydroxy groups gave novel highly functionalized indolizidines. The synthesis of a pyrroloazepine analogue is also described. Conclusion We have developed a new straightforward methodology for the synthesis of densely functionalized indolizidines and pyrroloazepine analogues in 6 steps and 30–60% overall yields from enantiopure hydroxylamines obtained straightforwardly from carbohydrate-derived nitrones. PMID:18076753

Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine.

PubMed

Bédard, Anne-Catherine; Longstreet, Ashley R; Britton, Joshua; Wang, Yuran; Moriguchi, Hideki; Hicklin, Robert W; Green, William H; Jamison, Timothy F

2017-12-01

Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9. Copyright © 2017 Elsevier Ltd. All rights reserved.

LiFePO4 Nanostructures Fabricated from Iron(III) Phosphate (FePO4 x 2H2O) by Hydrothermal Method.

PubMed

Saji, Viswanathan S; Song, Hyun-Kon

2015-01-01

Electrode materials having nanometer scale dimensions are expected to have property enhancements due to enhanced surface area and mass/charge transport kinetics. This is particularly relevant to intrinsically low electronically conductive materials such as lithium iron phosphate (LiFePO4), which is of recent research interest as a high performance intercalation electrode material for Li-ion batteries. Many of the reported works on LiFePO4 synthesis are unattractive either due to the high cost of raw materials or due to the complex synthesis technique. In this direction, synthesis of LiFePO4 directly from inexpensive FePO4 shows promise.The present study reports LiFePO4 nanostructures prepared from iron (III) phosphate (FePO4 x 2H2O) by precipitation-hydrothermal method. The sintered powder was characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), Inductive coupled plasma-optical emission spectroscopy (ICP-OES), and Electron microscopy (SEM and TEM). Two synthesis methods, viz. bulk synthesis and anodized aluminum oxide (AAO) template-assisted synthesis are reported. By bulk synthesis, micro-sized particles having peculiar surface nanostructuring were formed at precipitation pH of 6.0 to 7.5 whereas typical nanosized LiFePO4 resulted at pH ≥ 8.0. An in-situ precipitation strategy inside the pores of AAO utilizing the spin coating was utilized for the AAO-template-assisted synthesis. The template with pores filled with the precipitate was subsequently subjected to hydrothermal process and high temperature sintering to fabricate compact rod-like structures.

High-rate synthesis of Cu-BTC metal-organic frameworks.

PubMed

Kim, Ki-Joong; Li, Yong Jun; Kreider, Peter B; Chang, Chih-Hung; Wannenmacher, Nick; Thallapally, Praveen K; Ahn, Ho-Geun

2013-12-21

The reaction conditions for the synthesis of Cu-BTC (BTC = benzene-1,3,5-tricarboxylic acid) were elucidated using a continuous-flow microreactor-assisted solvothermal system to achieve crystal size and phase control. A high-rate synthesis of Cu-BTC metal-organic frameworks with a BET surface area of more than 1600 m(2) g(-1) (Langmuir surface area of more than 2000 m(2) g(-1)) and with a 97% production yield could be achieved with a total reaction time of 5 minutes.

Tailored fischer-tropsch synthesis product distribution

DOEpatents

Wang, Yong [Richland, WA; Cao, Chunshe [Kennewick, WA; Li, Xiaohong Shari [Richland, WA; Elliott, Douglas C [Richland, WA

2012-06-19

Novel methods of Fischer-Tropsch synthesis are described. It has been discovered that conducting the Fischer-Tropsch synthesis over a catalyst with a catalytically active surface layer of 35 microns or less results in a liquid hydrocarbon product with a high ratio of C.sub.5-C.sub.20:C.sub.20+. Descriptions of novel Fischer-Tropsch catalysts and reactors are also provided. Novel hydrocarbon compositions with a high ratio of C.sub.5-C.sub.20:C.sub.20+ are also described.

Facile room-temperature solution-phase synthesis of a spherical covalent organic framework for high-resolution chromatographic separation.

PubMed

Yang, Cheng-Xiong; Liu, Chang; Cao, Yi-Meng; Yan, Xiu-Ping

2015-08-07

A simple and facile room-temperature solution-phase synthesis was developed to fabricate a spherical covalent organic framework with large surface area, good solvent stability and high thermostability for high-resolution chromatographic separation of diverse important industrial analytes including alkanes, cyclohexane and benzene, α-pinene and β-pinene, and alcohols with high column efficiency and good precision.

Fischer-Tropsch Wastewater Utilization

DOEpatents

Shah, Lalit S.

2003-03-18

The present invention is generally directed to handling the wastewater, or condensate, from a hydrocarbon synthesis reactor. More particularly, the present invention provides a process wherein the wastewater of a hydrocarbon synthesis reactor, such as a Fischer-Tropsch reactor, is sent to a gasifier and subsequently reacted with steam and oxygen at high temperatures and pressures so as to produce synthesis gas. The wastewater may also be recycled back to a slurry preparation stage, where solid combustible organic materials are pulverized and mixed with process water and the wastewater to form a slurry, after which the slurry fed to a gasifier where it is reacted with steam and oxygen at high temperatures and pressures so as to produce synthesis gas.

Nanographene synthesis employing in-liquid plasmas with alcohols or hydrocarbons

NASA Astrophysics Data System (ADS)

Ando, Atsushi; Ishikawa, Kenji; Kondo, Hiroki; Tsutsumi, Takayoshi; Takeda, Keigo; Ohta, Takayuki; Ito, Masafumi; Hiramatsu, Mineo; Sekine, Makoto; Hori, Masaru

2018-02-01

Graphenes of nanometer-scale grain size (nanographenes) were synthesized using in-liquid plasmas with alcohols or hydrocarbons. This method of nanographene synthesis showed a trade-off relationship between crystallinity and synthesis rate. The high crystallinity of nanographenes synthesized with alcohols was evaluated from the small full width at half maxima (FWHM) of the G band in Raman scattering spectra. On the other hand, in the case of using hydrocarbons such as n-hexane and benzene, a significantly high synthesis rate was obtained but the crystallinity of nanographenes was low. It was found that hydroxyl groups and oxygen atoms of liquid sources play important roles in determining the crystallinity of synthesized nanographenes.

JPRS Report - Science & Technology Japan: New Functional Materials.

DTIC Science & Technology

1989-12-27

Using Modified and Controlled High Pressure Environments [Masao Wakatsuki, Kaoru J. Takano] 21 Molecular Design, Synthesis, and Evaluation of High...Crystals [ Shigetoshi Takahashi ] 51 Synthesis of New Organosilicon Polymers and Their Functionalities [Mitsuo Ishikawa , Joji Ohshita] 52...Analysis of The Formation Mechanisms Using Modified and Controlled High Pressure Environments Masao Wakatsuki and Kaoru J. Takano Institute of

A template-free solvent-mediated synthesis of high surface area boron nitride nanosheets for aerobic oxidative desulfurization.

PubMed

Wu, Peiwen; Zhu, Wenshuai; Chao, Yanhong; Zhang, Jinshui; Zhang, Pengfei; Zhu, Huiyuan; Li, Changfeng; Chen, Zhigang; Li, Huaming; Dai, Sheng

2016-01-04

Hexagonal boron nitride nanosheets (h-BNNs) with rather high specific surface area (SSA) are important two-dimensional layer-structured materials. Here, a solvent-mediated synthesis of h-BNNs revealed a template-free lattice plane control strategy that induced high SSA nanoporous structured h-BNNs with outstanding aerobic oxidative desulfurization performance.

Synthesis of Renewable Lubricant Alkanes from Biomass-Derived Platform Chemicals.

PubMed

Gu, Mengyuan; Xia, Qineng; Liu, Xiaohui; Guo, Yong; Wang, Yanqin

2017-10-23

The catalytic synthesis of liquid alkanes from renewable biomass has received tremendous attention in recent years. However, bio-based platform chemicals have not to date been exploited for the synthesis of highly branched lubricant alkanes, which are currently produced by hydrocracking and hydroisomerization of long-chain n-paraffins. A selective catalytic synthetic route has been developed for the production of highly branched C 23 alkanes as lubricant base oil components from biomass-derived furfural and acetone through a sequential four-step process, including aldol condensation of furfural with acetone to produce a C 13 double adduct, selective hydrogenation of the adduct to a C 13 ketone, followed by a second condensation of the C 13 ketone with furfural to generate a C 23 aldol adduct, and finally hydrodeoxygenation to give highly branched C 23 alkanes in 50.6 % overall yield from furfural. This work opens a general strategy for the synthesis of high-quality lubricant alkanes from renewable biomass. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adaptive changes in translation initiation activities for rat pancreatic protein synthesis with feeding of a high-protein diet.

PubMed

Hashi, Masaru; Yoshizawa, Fumiaki; Onozuka, Emi; Ogata, Momoko; Hara, Hiroshi

2005-08-01

We have previously demonstrated that dietary protein induced pancreatic hypergrowth in pancreaticobiliary diverted (PBD) rats. Dietary protein and dietary amino acids stimulate protein synthesis by regulating translation initiation in the rat skeletal muscle and liver. The aim of the present study was to determine whether feeding a high-protein diet induces activation of translation initiation for protein synthesis in the rat pancreas. In PBD rats in which the bile-pancreatic juice was surgically diverted to the upper ileum for 11-13 days, pancreatic dry weight and protein content were doubled compared with those in sham rats and further increased with feeding of a high-protein diet (60% casein diet) for 2 days. These pancreatic growth parameters were maintained at high levels for the next 5 days and were much higher than those of sham rats fed a high-protein diet. In both sham and PBD rats, feeding of a high-protein diet for 2 days induced phosphorylation of eukaryotic initiation factor 4E-binding protein 1 and 70-kDa ribosomal protein S6 kinase, indicating the activation of the initiation phase of translation for pancreatic protein synthesis. However, this increased phosphorylation returned to normal levels on Day 7 in PBD but not in sham rats. We concluded that feeding a high-protein diet induced pancreatic growth with increases in the translation initiation activities for pancreatic protein synthesis within 2 days and that prolonged feeding of a high-protein diet changed the initiation activities differently in sham and PBD rats.

Synthesis of Ultra-incompressible sp 3 -Hybridized Carbon Nitride with 1:1 Stoichiometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stavrou, Elissaios; Lobanov, Sergey; Dong, Huafeng

Search of materials with C-N composition hold a great promise in creating materials which would rival diamond hardness due to the very strong and relatively low-ionic C-N bond. Early experimental and theoretical works on C-N compounds were based on structural similarity with binary A 3B 4 structural types; however, the synthesis of C 3N 4 remains elusive. Here we explored an unbiased synthesis from the elemental materials at high pressures and temperatures. Using in situ synchrotron X-ray diffraction and Raman spectroscopy we demonstrate the synthesis of highly incompressible Pnnm CN compound with sp 3 hybridized carbon above 55 GPa andmore » 7000 K. This result is supported by first principles evolutionary search, which finds that Pnnm CN is the most stable compound above 10.9 GPa. On pressure release below 6 GPa the synthesized CN compound amorphizes reattaining its 1:1 stoichiometry as confirmed by Energy-Dispersive X-ray Spectroscopy. Here, this work underscores the importance of understanding of novel high-pressure chemistry rules and it opens a new route for synthesis of superhard materials.« less

Synthesis of Ultra-incompressible sp 3 -Hybridized Carbon Nitride with 1:1 Stoichiometry

DOE PAGES

Stavrou, Elissaios; Lobanov, Sergey; Dong, Huafeng; ...

2016-10-11

Search of materials with C-N composition hold a great promise in creating materials which would rival diamond hardness due to the very strong and relatively low-ionic C-N bond. Early experimental and theoretical works on C-N compounds were based on structural similarity with binary A 3B 4 structural types; however, the synthesis of C 3N 4 remains elusive. Here we explored an unbiased synthesis from the elemental materials at high pressures and temperatures. Using in situ synchrotron X-ray diffraction and Raman spectroscopy we demonstrate the synthesis of highly incompressible Pnnm CN compound with sp 3 hybridized carbon above 55 GPa andmore » 7000 K. This result is supported by first principles evolutionary search, which finds that Pnnm CN is the most stable compound above 10.9 GPa. On pressure release below 6 GPa the synthesized CN compound amorphizes reattaining its 1:1 stoichiometry as confirmed by Energy-Dispersive X-ray Spectroscopy. Here, this work underscores the importance of understanding of novel high-pressure chemistry rules and it opens a new route for synthesis of superhard materials.« less

Liver protein synthesis stays elevated after chemotherapy in tumour-bearing mice.

PubMed

Samuels, Sue E; McLaren, Teresa A; Knowles, Andrew L; Stewart, Sarah A; Madelmont, Jean-Claude; Attaix, Didier

2006-07-28

We studied the effect of chemotherapy on liver protein synthesis in mice bearing colon 26 adenocarcinoma (C26). Liver protein mass decreased (-32%; P<0.05) in cachectic mice, but protein synthesis increased (20-35%; P<0.05) in cachectic mice, which is consistent with increased export protein synthesis. Increased protein synthesis in tumour-bearing mice was primarily mediated by increasing ( approximately 15%; P<0.05) the RNA concentration, i.e. the capacity for protein synthesis (Cs; mg RNA/g protein). Cystemustine, a nitrosourea chemotherapy that cures C26 with 100% efficacy, rapidly restored liver protein mass; protein synthesis however stayed higher than in healthy mice ( approximately 15%) throughout the initial and later stages of recovery. Chemotherapy had no significant effect on liver protein mass and synthesis in healthy mice. Reduced food intake was not a factor in this model. These data suggest a high priority for liver protein synthesis during cancer cachexia and recovery.

Synthesis Can Take Many Forms

ERIC Educational Resources Information Center

Darrow, Rob

2005-01-01

Synthesis can take many forms at the high school level and from a Big6 perspective. Synthesis means purposeful, valuable and interesting assignments. It is very important for a classroom teacher to recognize that students can synthesize information several times during a project and that there are many different ways to present information.

Catalysis of the Carbonylation of Alcohols to Carboxylic Acids Including Acetic Acid Synthesis from Methanol.

ERIC Educational Resources Information Center

Forster, Denis; DeKleva, Thomas W.

1986-01-01

Monsanto's highly successful synthesis of acetic acid from methanol and carbon monoxide illustrates use of new starting materials to replace pretroleum-derived ethylene. Outlines the fundamental aspects of the acetic acid process and suggests ways of extending the synthesis to higher carboxylic acids. (JN)

Dietary salt loading increases nitric oxide synthesis in transgenic mice overexpressing sodium-proton exchanger.

PubMed

Kiraku, J; Nakamura, T; Sugiyama, T; Takahashi, N; Kuro-o, M; Fujii, J; Nagai, R

1999-06-01

We studied the role of nitric oxide (NO) synthesis in amelioration of blood pressure elevation during dietary salt loading in transgenic mice overexpressing sodium proton exchanger. Systolic blood pressure rose after starting salt loading only in the high-salt group of transgenic mice. However, this elevation of blood pressure was not continued. Urinary excretion of inorganic nitrite and nitrate in the high-salt group of transgenic mice was significantly higher than in the high-salt group of control mice. These results suggest that increased NO synthesis in response to salt loading is one of the anti-hypertensive mechanisms in transgenic mice overexpressing sodium proton exchanger.

Rapid Size- Controlled Synthesis of Dextran-Coated, Copper-Doped Iron Oxide Nanoparticles

NASA Astrophysics Data System (ADS)

Wong, Ray M.

2011-12-01

Development of dual modality probes enabled for magnetic resonance imaging (MRI) and positron emission tomography (PET) has been on the rise in recent years due to the potential for these probes to facilitate combining the complementary high resolution of MRI and the high sensitivity of PET. The efficient synthesis of multimodal probes that include the radiolabels for PET can be hindered due to prolonged reaction times during radioisotope incorporation, and the resulting decay of the radiolabel. Along with a time-efficient synthesis, one also needs an optimal synthesis that yields products in a desirable size range (between 20-100 nm) to increase blood retention time. In this work, we describe a novel, rapid, microwave-based synthesis of dextran-coated iron oxide nanoparticles doped with copper (DIO/Cu). Traditional methods for synthesizing dextran-coated iron oxide particles require refluxing for 2 hours and result in approximately 50 nm particles. We demonstrate that microwave synthesis can produce 50 nm nanoparticles in 5 minutes of heating. We discuss the various parameters used in the microwave synthesis protocol to vary the size distribution of DIO/Cu, and demonstrate the successful incorporation of copper into these particles with the aim of future use for rapid 64Cu incorporation.

Nutritional Requirements for Synthesis of Heat-Labile Enterotoxin by Enterotoxigenic Strains of Escherichia coli

PubMed Central

Gilligan, Peter H.; Robertson, Donald C.

1979-01-01

Optimal growth conditions have been established for production of heat-labile enterotoxin (LT) by both porcine and human strains of enterotoxigenic (ENT+) Escherichia coli. There were no unusual growth factor requirements, and some strains produced fairly high levels of LT in a basal salts medium containing 0.5% glucose if the pH was carefully controlled. Several amino acids markedly stimulated LT synthesis when added to the basal salts-glucose medium. Methionine and lysine were the most stimulatory for both human and porcine strains. Either aspartic acid or glutamic acid further enhanced LT synthesis in the presence of methionine and lysine, with aspartic acid being more stimulatory for porcine strains and glutamic acid more stimulatory for human strains. There were no apparent vitamin requirements and no unusual cations needed for toxin synthesis except that Fe3+ was slightly stimulatory for porcine strains. The stimulation by Fe3+ was observed only in the presence of the three amino acids, suggesting that the effect was indirect rather than on toxin synthesis. The carbon source also influenced the yield of LT. Glucose supported maximal synthesis, but other carbon sources which exhibit a high degree of catabolite repression also supported high levels of synthesis. Little or no LT was released below pH 7.0; therefore, because the pH drops during growth from 7.5 to 6.8, even in highly buffered media, it was necessary to adjust the pH to 8.0 to effect complete release of cell-associated toxin. The defined medium containing three amino acids reduced the amount of UV-absorbing material in culture supernatants about fivefold and increased LT activity for various strains from two- to fivefold over a complex Casamino Acids-yeast extract medium. Conditions found to be optimal for synthesis of LT were inhibitory for the heat-stable enterotoxin. PMID:33900

Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units

NASA Astrophysics Data System (ADS)

Wu, Yong; Xiong, De-Cai; Chen, Si-Cong; Wang, Yong-Shi; Ye, Xin-Shan

2017-03-01

Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent [31+31+30] coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.

High-throughput continuous hydrothermal synthesis of nanomaterials (part II): unveiling the as-prepared CexZryYzO2-δ phase diagram.

PubMed

Quesada-Cabrera, Raul; Weng, Xiaole; Hyett, Geoff; Clark, Robin J H; Wang, Xue Z; Darr, Jawwad A

2013-09-09

High-throughput continuous hydrothermal flow synthesis was used to manufacture 66 unique nanostructured oxide samples in the Ce-Zr-Y-O system. This synthesis approach resulted in a significant increase in throughput compared to that of conventional batch or continuous hydrothermal synthesis methods. The as-prepared library samples were placed into a wellplate for both automated high-throughput powder X-ray diffraction and Raman spectroscopy data collection, which allowed comprehensive structural characterization and phase mapping. The data suggested that a continuous cubic-like phase field connects all three Ce-Zr-O, Ce-Y-O, and Y-Zr-O binary systems together with a smooth and steady transition between the structures of neighboring compositions. The continuous hydrothermal process led to as-prepared crystallite sizes in the range of 2-7 nm (as determined by using the Scherrer equation).

High-Yield Synthesis and Applications of Anisotropic Gold Nanoparticles

NASA Astrophysics Data System (ADS)

Vigderman, Leonid

This work will describe research directed towards the synthesis of anisotropic gold nanoparticles as well as their functionalization and biological applications. The thesis will begin by describing a new technique for the high-yield synthesis of gold nanorods using hydroquinone as a reducing agent. This addresses important limitations of the traditional nanorod synthesis including low yield of gold ions conversion to metallic form and inability to produce rods with longitudinal surface plasmon peak above 850 nm. The use of hydroquinone was also found to improve the synthesis of gold nanowires via the nanorod-seed mediated procedure developed in our lab. The thesis will next present the synthesis of novel starfruitshaped nanorods, mesorods, and nanowires using a modified nanorod-seed mediated procedure. The starfruit particles displayed increased activity as surfaceenhanced Raman spectroscopy (SERS) substrates as compared to smooth structures. Next, a method for the functionalization of gold nanorods using a cationic thiol, 16-mercaptohexadecyltrimethylammonium bromide (MTAB), will be described. By using this thiol, we were able to demonstrate the complete removal of toxic surfactant from the nanorods and were also able to precisely quantify the grafting density of thiol molecules on the nanorod surface through a combination of several analytical techniques. Finally, this thesis will show that MTABfunctionalized nanorods are nontoxic and can be taken up in extremely high numbers into cancer cells. The thesis will conclude by describing the surprising uptake of larger mesorods and nanowires functionalized with MTAB into cells in high quantities.

Synthesis of PD particles by alcohols-assisted photoreduction for use in supported catalysts

DOEpatents

Burton, Patrick David; Boyle, Timothy J; Datye, Abhaya

2015-02-24

The present disclosure provides a novel synthesis method for palladium nanoparticles and palladium nanoparticles made using the method. The nanoparticles resulting from the method are highly reactive and, when deposited on a support, are highly suitable for use as catalytic material.

Habituation to low or high protein intake does not modulate basal or postprandial muscle protein synthesis rates: a randomized trial.

PubMed

Gorissen, Stefan Hm; Horstman, Astrid Mh; Franssen, Rinske; Kouw, Imre Wk; Wall, Benjamin T; Burd, Nicholas A; de Groot, Lisette Cpgm; van Loon, Luc Jc

2017-02-01

Muscle mass maintenance is largely regulated by basal muscle protein synthesis rates and the ability to increase muscle protein synthesis after protein ingestion. To our knowledge, no previous studies have evaluated the impact of habituation to either low protein intake (LOW PRO) or high protein intake (HIGH PRO) on the postprandial muscle protein synthetic response. We assessed the impact of LOW PRO compared with HIGH PRO on basal and postprandial muscle protein synthesis rates after the ingestion of 25 g whey protein. Twenty-four healthy, older men [age: 62 ± 1 y; body mass index (in kg/m 2 ): 25.9 ± 0.4 (mean ± SEM)] participated in a parallel-group randomized trial in which they adapted to either a LOW PRO diet (0.7 g · kg -1 · d -1 ; n = 12) or a HIGH PRO diet (1.5 g · kg -1 · d -1 ; n = 12) for 14 d. On day 15, participants received primed continuous l-[ring- 2 H 5 ]-phenylalanine and l-[1- 13 C]-leucine infusions and ingested 25 g intrinsically l-[1- 13 C]-phenylalanine- and l-[1- 13 C]-leucine-labeled whey protein. Muscle biopsies and blood samples were collected to assess muscle protein synthesis rates as well as dietary protein digestion and absorption kinetics. Plasma leucine concentrations and exogenous phenylalanine appearance rates increased after protein ingestion (P < 0.01) with no differences between treatments (P > 0.05). Plasma exogenous phenylalanine availability over the 5-h postprandial period was greater after LOW PRO than after HIGH PRO (61% ± 1% compared with 56% ± 2%, respectively; P < 0.05). Muscle protein synthesis rates increased from 0.031% ± 0.004% compared with 0.039% ± 0.007%/h in the fasted state to 0.062% ± 0.005% compared with 0.057% ± 0.005%/h in the postprandial state after LOW PRO compared with HIGH PRO, respectively (P < 0.01), with no differences between treatments (P = 0.25). Habituation to LOW PRO (0.7 g · kg -1 · d -1 ) compared with HIGH PRO (1.5 g · kg -1 · d -1 ) augments the postprandial availability of dietary protein-derived amino acids in the circulation and does not lower basal muscle protein synthesis rates or increase postprandial muscle protein synthesis rates after ingestion of 25 g protein in older men. This trial was registered at clinicaltrials.gov as NCT01986842. © 2017 American Society for Nutrition.

Synthesis and Chemistry of Novel Cyclic Fluorocarbons

DTIC Science & Technology

1993-05-27

Perfluorosemibulvalene " Part II. "Synthesis and Studies of Perfluorobenzene Oxide / Perfluorooxepin ", 199 Correa, R.A., "Synthesis of Highly Fluorinated Bicyclo... Perfluorotmne . In the course of attempts to develop a more practical synthesis of the perfluorotropylium ion (21) than our original route, we found a new...34, J. Org. Chem. 1991,56, 157-60. 8. Takenaka, N.E.; Lemal, D.M. "The Perfluorobenzene Oxide/ Perfluorooxepin System" in Synthetic Fluorine Chemistry

A template-free solvent-mediated synthesis of high surface area boron nitride nanosheets for aerobic oxidative desulfurization

DOE PAGES

Wu, Peiwen; Zhu, Wenshuai; Chao, Yanhong; ...

2015-10-16

Hexagonal boron nitride nanosheets (h-BNNs) with rather high specific surface area (SSA) are important two-dimensional layer-structured materials. Here in this study, a solvent-mediated synthesis of h-BNNs revealed a template-free lattice plane control strategy that induced high SSA nanoporous structured h-BNNs with outstanding aerobic oxidative desulfurization performance.

Multicomponent Macrocyclization Reactions (MCMRs) Employing Highly Reactive Acyl Ketene and Nitrile Oxide Intermediates

PubMed Central

Knapp, John M.; Fettinger, James C.; Kurth, Mark J.

2011-01-01

An efficient synthesis of spiro-fused macrolactams by a multicomponent macrocyclization reaction (MCMR) is reported. The use of highly reactive, transient intermediates in this MCMR permits short reaction times, even at high dilution. The methods employed for this MCMR were first developed as a four component strategy for the synthesis of β-ketoamide isoxazolines. PMID:21827181

Differential regulation of protein synthesis by amino acids and insulin in peripheral and visceral tissues of neonatal pigs

PubMed Central

Suryawan, Agus; O’Connor, Pamela M. J.; Bush, Jill A.; Nguyen, Hanh V.

2009-01-01

The high efficiency of protein deposition during the neonatal period is driven by high rates of protein synthesis, which are maximally stimulated after feeding. In the current study, we examined the individual roles of amino acids and insulin in the regulation of protein synthesis in peripheral and visceral tissues of the neonate by performing pancreatic glucose–amino acid clamps in overnight-fasted 7-day-old pigs. We infused pigs (n = 8–12/group) with insulin at 0, 10, 22, and 110 ng kg−0.66 min−1 to achieve ~0, 2, 6 and 30 μU ml−1 insulin so as to simulate below fasting, fasting, intermediate, and fed insulin levels, respectively. At each insulin dose, amino acids were maintained at the fasting or fed level. In conjunction with the highest insulin dose, amino acids were also allowed to fall below the fasting level. Tissue protein synthesis was measured using a flooding dose of L-[4-3H] phenylalanine. Both insulin and amino acids increased fractional rates of protein synthesis in longissimus dorsi, gastrocnemius, masseter, and diaphragm muscles. Insulin, but not amino acids, increased protein synthesis in the skin. Amino acids, but not insulin, increased protein synthesis in the liver, pancreas, spleen, and lung and tended to increase protein synthesis in the jejunum and kidney. Neither insulin nor amino acids altered protein synthesis in the stomach. The results suggest that the stimulation of protein synthesis by feeding in most tissues of the neonate is regulated by the post-prandial rise in amino acids. However, the feeding-induced stimulation of protein synthesis in skeletal muscles is independently mediated by insulin as well as amino acids. PMID:18683020

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...

Synthesis of organosilicon compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, G.

1996-01-01

Silicon-containing polymers have been a focus of synthesis and study in Dr. Barton`s group because of their chemistry and properties which are not offered by other systems or materials. For example, the polymer -[-SiMe 2C≡C-] n-can be easily processed to films or fibers from melt or solution, and thermally converted to a SiC-containing ceramic in high yield at high temperature. In recent years, carbosilane dendritic polymers have been of great interests in many research groups. However, no synthesis of carbosilane dendrimers with functionalties both inside and outside the dendrimer has been reported. Functionality is very important in the synthesis ofmore » preceramic polymers. This thesis will be devoted to exploring several new organosilicon polymer systems.« less

Estimation of in vitro activity of tuberoinfundibular dopaminergic neurons by measurement of DOPA synthesis in the median eminence of hypothalamic slices.

PubMed

Arita, J; Kimura, F

1984-12-01

A new method for estimation of in vitro neurosecretory activity of tuberoinfundibular dopaminergic (TIDA) neurons was developed by measuring the rate of synthesis of dihydroxyphenylalanine (DOPA) in the median eminence of hypothalamic slices. Sagittal hypothalamic slices of ovariectomized rats were incubated in a medium containing 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of DOPA decarboxylase. DOPA accumulated in the median eminence following incubation with NSD 1015 was determined by high-performance liquid chromatography with electro-chemical detection. The amount of DOPA accumulated in vitro in the median eminence was maximal in a medium containing 10 mM NSD 1015 and linear up to 120 min at 37 degrees C. Increasing the concentration of tyrosine in medium stimulated the synthesis of DOPA in the median eminence. The synthesis of DOPA was blocked by 1 mM alpha-methyltyrosine, an inhibitor of tyrosine hydroxylase. The rate of in vitro synthesis of DOPA in the median eminence was 33% of that of in vivo synthesis. Incubation in a medium containing 50 mM K+ to depolarize neurons caused a 2.4-fold increase in DOPA synthesis in the median eminence. The high K+-induced increase in DOPA synthesis was blocked by omission of Ca2+ and addition of 1 mM EGTA into the medium, suggesting Ca2+ dependency of depolarization-activated DOPA synthesis. These results indicate that this in vitro assay is a useful means to study the regulatory mechanisms of TIDA neurons.

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

USDA-ARS?s Scientific Manuscript database

In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study...

Total Synthesis of (+)- and (±)-Hosieine A.

PubMed

Huang, Yu-Wen; Kong, Ke; Wood, John

2018-05-03

Described here is a concise total synthesis of the highly potent nicotinic acetylcholine receptor antagonist hosieine A in racemic ((±)-2) and enantioenriched ((+)-2) forms. The synthesis requires only 7-steps and features a telescoped reaction sequence initiated by a gold-catalyzed Rautenstrauch reaction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

PubMed

Chung, T; Huang, J S; Mukherjee, J J; Crilly, K S; Kiss, Z

2000-05-01

In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

Synthesis of a new class of Betti bases by the Mannich-type reaction: efficient, facile, solvent-free and one-pot protocol.

PubMed

Shahrisa, Aziz; Teimuri-Mofrad, Reza; Gholamhosseini-Nazari, Mahdi

2015-02-01

A variety of organocatalysts has been screened for the synthesis of arylaminonaphthols. It has been shown that (N,N-dimethylethanolamine) is a highly efficient organocatalyst for the direct synthesis of a novel class of arylaminonaphthols via three-component condensation of 2-naphthol, aldehydes, and arylamines under solvent-free conditions. Mild, one-pot, and green reaction conditions, relatively short reaction times and good yields make this protocol highly significant. 25 new compounds have been synthesized by this method.

Versatile, High Quality and Scalable Continuous Flow Production of Metal-Organic Frameworks

PubMed Central

Rubio-Martinez, Marta; Batten, Michael P.; Polyzos, Anastasios; Carey, Keri-Constanti; Mardel, James I.; Lim, Kok-Seng; Hill, Matthew R.

2014-01-01

Further deployment of Metal-Organic Frameworks in applied settings requires their ready preparation at scale. Expansion of typical batch processes can lead to unsuccessful or low quality synthesis for some systems. Here we report how continuous flow chemistry can be adapted as a versatile route to a range of MOFs, by emulating conditions of lab-scale batch synthesis. This delivers ready synthesis of three different MOFs, with surface areas that closely match theoretical maxima, with production rates of 60 g/h at extremely high space-time yields. PMID:24962145

Stereoselective Synthesis of trans-Olefins by the Copper-Mediated SN2′ Reaction of Vinyl Oxazines with Grignard Reagents. Asymmetric Synthesis of D-threo-Sphingosines

PubMed Central

Singh, Om V.; Han, Hyunsoo

2007-01-01

The SN2′ reaction of 6-vinyl-5,6-dihydro-4H-[1,3]oxazines with Grignard reagents in the presence of CuCN was studied, and high trans selectivity for the formation of double bond was observed with a variety of RMgX. The SN2′ reaction, coupled with regioselective asymmetric aminohydroxylation reaction, provided a highly efficient route for the asymmetric synthesis of D-threo-N-acetylsphingosine. PMID:18958293

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines - application to a formal synthesis of sarizotan.

PubMed

Gati, Wafa; Rammah, Mohamed M; Rammah, Mohamed B; Evano, Gwilherm

2012-01-01

We have developed a general synthesis of polysubstituted 1,4-dihydropyridines and pyridines based on a highly regioselective lithiation/6-endo-dig intramolecular carbolithiation from readily available N-allyl-ynamides. This reaction, which has been successfully applied to the formal synthesis of the anti-dyskinesia agent sarizotan, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions.

Photocontrol of Anthocyanin Synthesis

PubMed Central

Mancinelli, A. L.; Yang, Chia-Ping Huang; Lindquist, P.; Anderson, O. R.; Rabino, I.

1975-01-01

Streptomycin enhances the synthesis of anthocyanins and inhibits the synthesis of chlorophylls and the development of chloroplasts in dark-grown seedlings of cabbage (Brassica oleracea), mustard (Sinapis alba), tomato (Lycopersicon esculentum), and turnip (Brassica rapa) exposed to prolonged periods of irradiation in various spectral regions. These results suggest that the contribution of photosynthesis to light-dependent high irradiance reaction anthocyanin synthesis in seedlings of cabbage, mustard, tomato, and turnip is minimal, if any at all. So far, phytochrome is the only photoreceptor whose action in the control of light-dependent anthocyanin synthesis in seedlings of cabbage, mustard, tomato, and turnip has been satisfactorily demonstrated. Images PMID:16659061

Protein Synthesis in Relation to Ripening of Pome Fruits 1

PubMed Central

Frenkel, Chaim; Klein, Isaac; Dilley, D. R.

1968-01-01

Protein synthesis by intact Bartlett pear fruits was studied with ripening as measured by flesh softening, chlorophyll degradation, respiration, ethylene synthesis, and malic enzyme activity. Protein synthesis is required for normal ripening, and the proteins synthesized early in the ripening process are, in fact, enzymes required for ripening. 14C-Phenylalanine is differentially incorporated into fruit proteins separated by acrylamide gel electrophoresis of pome fruits taken at successive ripening stages. Capacity for malic enzyme synthesis increases during the early stage of ripening. Fruit ripening and ethylene synthesis are inhibited when protein synthesis is blocked by treatment with cycloheximide at the early-climacteric stage. Cycloheximide became less effective as the climacteric developed. Ethylene did not overcome inhibition of ripening by cycloheximide. The respiratory climacteric is not inhibited by cycloheximide. It is concluded that normal ripening of pome fruits is a highly coordinated process of biochemical differentiation involving directed protein synthesis. PMID:16656897

Facile and green synthesis of highly stable L-cysteine functionalized copper nanoparticles

NASA Astrophysics Data System (ADS)

Kumar, Nikhil; Upadhyay, Lata Sheo Bachan

2016-11-01

A simple eco-friendly method for L-cysteine capped copper nanoparticles (CCNPs) synthesis in aqueous solution has been developed. Glucose and L-cysteine were used as reducing agent and capping/functionalizing agent, respectively. Different parameters such as capping agent concentration, pH, reaction temperature, and reducing agent concentration were optimized during the synthesis. The L-cysteine capped copper nanoparticle were characterized by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, Particle size and zeta potential analyser, and high resolution transmission electron microscopy. Spherical shaped cysteine functionalized/capped copper nanoparticles with an average size of 40 nm were found to be highly stable at room temperature (RT) for a period of 1 month

Synthesis and Primary Characterization of Self-Assembled Peptide-Based Hydrogels

PubMed Central

Nagarkar, Radhika P.; Schneider, Joel P.

2009-01-01

Summary Hydrogels based on peptide self-assembly form an important class of biomaterials that find application in tissue engineering and drug delivery. It is essential to prepare peptides with high purity to achieve batch-to-batch consistency affording hydrogels with reproducible properties. Automated solid-phase peptide synthesis coupled with optimized Fmoc (9-fluorenylmethoxycarbonyl) chemistry to obtain peptides in high yield and purity is discussed. Details of isolating a desired peptide from crude synthetic mixtures and assessment of the peptide’s final purity by high-performance liquid chromatography and mass spectrometry are provided. Beyond the practical importance of synthesis and primary characterization, techniques used to investigate the properties of hydrogels are briefly discussed. PMID:19031061

Controlled Synthesis of Atomically Layered Hexagonal Boron Nitride via Chemical Vapor Deposition.

PubMed

Liu, Juanjuan; Kutty, R Govindan; Liu, Zheng

2016-11-29

Hexagonal boron nitrite (h-BN) is an attractive material for many applications including electronics as a complement to graphene, anti-oxidation coatings, light emitters, etc. However, the synthesis of high-quality h-BN is still a great challenge. In this work, via controlled chemical vapor deposition, we demonstrate the synthesis of h-BN films with a controlled thickness down to atomic layers. The quality of as-grown h-BN is confirmed by complementary characterizations including high-resolution transition electron microscopy, atomic force microscopy, Raman spectroscopy and X-ray photo-electron spectroscopy. This work will pave the way for production of large-scale and high-quality h-BN and its applications as well.

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

PubMed Central

Telang, Nakul S; Kong, Caleb J; Verghese, Jenson; Gilliland III, Stanley E; Ahmad, Saeed; Dominey, Raymond N

2018-01-01

Numerous synthetic methods for the continuous preparation of fine chemicals and active pharmaceutical ingredients (API’s) have been reported in recent years resulting in a dramatic improvement in process efficiencies. Herein we report a highly efficient continuous synthesis of the antimalarial drug hydroxychloroquine (HCQ). Key improvements in the new process include the elimination of protecting groups with an overall yield improvement of 52% over the current commercial process. The continuous process employs a combination of packed bed reactors with continuous stirred tank reactors for the direct conversion of the starting materials to the product. This high-yielding, multigram-scale continuous synthesis provides an opportunity to achieve increase global access to hydroxychloroquine for treatment of malaria. PMID:29623120

Noble gas trapping and fractionation during synthesis of carbonaceous matter. [in meteorites

NASA Technical Reports Server (NTRS)

Frick, U.; Mack, R.; Chang, S.

1979-01-01

An investigation of noble gas entrapment during synthesis of carbonaceous, macromolecular, and kerogen-like substances is presented. High molecular weight organic matter synthesized in aqueous condensation reactions contained little gas, and the composition was consistent with fractionation due to noble gas solubility in water; however, propane soot produced during a modified Miller-Urey experiment in an aritificial gas mixture contained high concentrations of trapped noble gases that displayed strong elemental fractionation from their reservoirs. It is concluded that theses experiemnts show that processes exist for synthesis of carbonaceous carriers that result in high noble gas concentrations and strong elemental fractionation at temperatures well above those required by absorption to achieve similar effects.

Magnetic nanoparticle supported phosphotungstic acid: An efficient catalyst for the synthesis of xanthene derivatives

NASA Astrophysics Data System (ADS)

Patel, Nipun; Katheriya, Deepak; Dadhania, Harsh; Dadhania, Abhishek

2018-05-01

Magnetic nanoparticle supported phosphotungstic acid (Fe3O4@SiO2-HPW) was applied as a highly efficient catalyst for the synthesis of 14H-dibenzoxanthene derivatives via condensation reaction of 2-naphthol and aryl aldehydes. The catalyst was found highly efficient for the synthesis of xanthene derivatives under solvent free condition. The catalyst showed high activity and stability during the reaction and provided excellent yield of the corresponding products in short reaction time. All the synthesized compounds were characterized through FT-IR, 1H-NMR and 13C-NMR spectroscopic techniques. Furthermore, the catalyst is magnetically recoverable and can be reused several times without significant loss of its catalytic activity.

The flavoprotein Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishimura, Akira; Kawahara, Nobuhiro; Takagi, Hiroshi, E-mail: hiro@bs.naist.jp

Highlights: Black-Right-Pointing-Pointer NO is produced from L-arginine in response to elevated temperature in yeast. Black-Right-Pointing-Pointer Tah18 was first identified as the yeast protein involved in NO synthesis. Black-Right-Pointing-Pointer Tah18-dependent NO synthesis confers tolerance to high-temperature on yeast cells. -- Abstract: Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. In the unicellular eukaryote yeast, NO may be involved in stress response pathways, but its role is poorly understood due to the lack of mammalian NO synthase (NOS) orthologues. Previously, we have proposed the oxidative stress-induced L-arginine synthesis and its physiologicalmore » role under stress conditions in yeast Saccharomyces cerevisiae. Here, our experimental results indicated that increased conversion of L-proline into L-arginine led to NO production in response to elevated temperature. We also showed that the flavoprotein Tah18, which was previously reported to transfer electrons to the Fe-S cluster protein Dre2, was involved in NO synthesis in yeast. Gene knockdown analysis demonstrated that Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells. As it appears that such a unique cell protection mechanism is specific to yeasts and fungi, it represents a promising target for antifungal activity.« less

Demonstration of diet-induced decoupling of fatty acid and cholesterol synthesis by combining gene expression array and 2H2O quantification.

PubMed

Jensen, Kristian K; Previs, Stephen F; Zhu, Lei; Herath, Kithsiri; Wang, Sheng-Ping; Bhat, Gowri; Hu, Guanghui; Miller, Paul L; McLaren, David G; Shin, Myung K; Vogt, Thomas F; Wang, Liangsu; Wong, Kenny K; Roddy, Thomas P; Johns, Douglas G; Hubbard, Brian K

2012-01-15

The liver is a crossroad for metabolism of lipid and carbohydrates, with acetyl-CoA serving as an important metabolic intermediate and a precursor for fatty acid and cholesterol biosynthesis pathways. A better understanding of the regulation of these pathways requires an experimental approach that provides both quantitative metabolic flux measurements and mechanistic insight. Under conditions of high carbohydrate availability, excess carbon is converted into free fatty acids and triglyceride for storage, but it is not clear how excessive carbohydrate availability affects cholesterol biosynthesis. To address this, C57BL/6J mice were fed either a low-fat, high-carbohydrate diet or a high-fat, carbohydrate-free diet. At the end of the dietary intervention, the two groups received (2)H(2)O to trace de novo fatty acid and cholesterol synthesis, and livers were collected for gene expression analysis. Expression of lipid and glucose metabolism genes was determined using a custom-designed pathway focused PCR-based gene expression array. The expression analysis showed downregulation of cholesterol biosynthesis genes and upregulation of fatty acid synthesis genes in mice receiving the high-carbohydrate diet compared with the carbohydrate-free diet. In support of these findings, (2)H(2)O tracer data showed that fatty acid synthesis was increased 10-fold and cholesterol synthesis was reduced by 1.6-fold in mice fed the respective diets. In conclusion, by applying gene expression analysis and tracer methodology, we show that fatty acid and cholesterol synthesis are differentially regulated when the carbohydrate intake in mice is altered.

Effects of nutritional state, aging and high chronic intake of sucrose on brain protein synthesis in rats: modulation of it by rutin and other micronutrients.

PubMed

Gatineau, Eva; Cluzet, Stéphanie; Krisa, Stéphanie; Papet, Isabelle; Migne, Carole; Remond, Didier; Dardevet, Dominique; Polakof, Sergio; Richard, Tristan; Mosoni, Laurent

2018-05-23

Little is still known about brain protein synthesis. In order to increase our knowledge of it, we aimed to modulate brain protein synthesis rates through aging, variations in nutritional state (fed state vs. fasted state), high sucrose diet and micronutrient supplementation. Four groups of 16 month-old male rats were fed for five months with a diet containing either 13% or 62% sucrose (wheat starch was replaced with sucrose), supplemented or not with rutin (5 g kg-1 diet), vitamin E (4×), A (2×), D (5×), selenium (10×) and zinc (+44%) and compared with an adult control group. We measured cerebellum protein synthesis and hippocampus gene expression of antioxidant enzymes, inflammatory cytokines and transcription factors. We showed that cerebellum protein synthesis was unchanged by the nutritional state, decreased during aging (-8%), and restored to the adult level by micronutrient supplementation. Sucrose diet did not change protein synthesis but reduced the protein content. Micronutrient supplementation had no effect in sucrose fed rats. Hippocampus gene expressions were affected by age (an increase of TNF-α), sucrose treatment (an increase of IL-1β and IL-6), and micronutrient supplementation (a decrease of heme oxygenase, catalase, glutathione peroxidase, TNF-α, and Nrf2). We noted that cerebellum protein synthesis and hippocampus TNF-α gene expression were modulated by the same factors: they were affected by aging and micronutrient supplementation and unchanged by feeding and by high sucrose diet.

A facile approach to the synthesis of highly electroactive Pt nanoparticles on graphene as an anode catalyst for direct methanol fuel cells.

PubMed

Zhou, Yi-Ge; Chen, Jing-Jing; Wang, Feng-bin; Sheng, Zhen-Huan; Xia, Xing-Hua

2010-08-28

A one-step electrochemical approach to the synthesis of highly dispersed Pt nanoparticles on graphene has been proposed. The resultant Pt NPs@G nanocomposite shows higher electrocatalytic activity and long-term stability towards methanol electrooxidation than the Pt NPs@Vulcan.

Highly oxidized superconductors

DOEpatents

Morris, D.E.

1994-09-20

Novel superconducting materials in the form of compounds, structures or phases are formed by performing otherwise known synthesis in a highly oxidizing atmosphere rather than that created by molecular oxygen at atmospheric pressure or below. This leads to the successful synthesis of novel superconducting compounds which are thermodynamically stable at the conditions under which they are formed. 16 figs.

Approach to Rapid Synthesis and Functionalization of Iron Oxide Nanoparticles for High Gene Transfection.

PubMed

Stephen, Zachary R; Dayringer, Christopher J; Lim, Josh J; Revia, Richard A; Halbert, Mackenzie V; Jeon, Mike; Bakthavatsalam, Arvind; Ellenbogen, Richard G; Zhang, Miqin

2016-03-01

Surface functionalization of theranostic nanoparticles (NPs) typically relies on lengthy, aqueous postsynthesis labeling chemistries that have limited ability to fine-tune surface properties and can lead to NP heterogeneity. The need for a rapid, simple synthesis approach that can provide great control over the display of functional moieties on NP surfaces has led to increased use of highly selective bioorthoganol chemistries including metal-affinity coordination. Here we report a simple approach for rapid production of a superparamagnetic iron oxide NPs (SPIONs) with tunable functionality and high reproducibility under aqueous conditions. We utilize the high affinity complex formed between catechol and Fe((III)) as a means to dock well-defined catechol modified polymer modules on the surface of SPIONs during sonochemical coprecipitation synthesis. Polymer modules consisted of chitosan and poly(ethylene glycol) (PEG) copolymer (CP) modified with catechol (CCP), and CCP functionalized with cationic polyethylenimine (CCP-PEI) to facilitate binding and delivery of DNA for gene therapy. This rapid synthesis/functionalization approach provided excellent control over the extent of PEI labeling, improved SPION magnetic resonance imaging (MRI) contrast enhancement and produced an efficient transfection agent.

Synthesis of single-site copper catalysts for methane partial oxidation

DOE PAGES

Grundner, S.; Luo, W.; Sanchez-Sanchez, M.; ...

2015-12-24

Cu-Exchanged zeolites are known as active materials for methane oxidation to methanol. However, understanding of the formation of Cu active species during synthesis, dehydration and activation is fragmented and rudimentary. We show here how a synthesis protocol guided by insight in the ion exchange elementary steps leads to highly uniform Cu species in mordenite (MOR).

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

PubMed Central

Gati, Wafa; Rammah, Mohamed M; Rammah, Mohamed B

2012-01-01

Summary We have developed a general synthesis of polysubstituted 1,4-dihydropyridines and pyridines based on a highly regioselective lithiation/6-endo-dig intramolecular carbolithiation from readily available N-allyl-ynamides. This reaction, which has been successfully applied to the formal synthesis of the anti-dyskinesia agent sarizotan, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions. PMID:23365632

Organocatalytic asymmetric anti-selective Michael reactions of aldehydes and the sequential reduction/lactonization/Pauson-Khand reaction for the enantioselective synthesis of highly functionalized hydropentalenes.

PubMed

Hong, Bor-Cherng; Dange, Nitin S; Yen, Po-Jen; Lee, Gene-Hsiang; Liao, Ju-Hsiou

2012-10-19

A new method has been developed for the enantioselective synthesis of highly functionalized hydropentalenes bearing up to four stereogenic centers with high stereoselectivity (up to 99% ee). This process combines an enantioselective organocatalytic anti-selective Michael addition with a highly efficient one-pot reduction/lactonization/Pauson-Khand reaction sequence. The structures and absolute configurations of the products were confirmed by X-ray analysis.

Regular Mechanical Transformation of Rotations Into Translations: Part 2. Kinematic Synthesis of the Elements of High Kinematic Joints, Realizing the Process of Motions Transformation

NASA Astrophysics Data System (ADS)

Abadjieva, Emilia; Abadjiev, Valentin

2017-09-01

This work is developed on the basis of the illustrated main parts of the kinematic theory (theory of gearing) of the spatial rack drives in Part 1 of this study. The applied theoretical approach to their synthesis, based on the T. Olivier's second principle is defined. A study of the geometric nature of the surface of action (mesh region, respectively) of these class transmissions is shown. Research software programs for synthesis and visualization of these transmissions and their specific elements are elaborated, on the basis of the given algorithms to the synthesis of the elements of high kinematic joints (active tooth surfaces), with which the movable links of the studied gear systems are equipped.

Super-hierarchical porous carbons derived from mixed biomass wastes by a stepwise removal strategy for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Peng, Lin; Liang, Yeru; Dong, Hanwu; Hu, Hang; Zhao, Xiao; Cai, Yijing; Xiao, Yong; Liu, Yingliang; Zheng, Mingtao

2018-02-01

The synthesis and energy storage application of hierarchical porous carbons with size ranging from nano-to micrometres has attracted considerable attention all over the world. Exploring eco-friendly and reliable synthesis of hierarchical porous carbons for supercapacitors with high energy density and high power is still of ongoing challenge. In this work, we report the design and synthesis of super-hierarchical porous carbons with highly developed porosity by a stepwise removal strategy for high-rate supercapacitors. The mixed biomass wastes of coconut shell and sewage sludge are employed as raw material. The as-prepared super-hierarchical porous carbons present high surface areas (3003 m2 g-1), large pore volume (2.04 cm3 g-1), appropriate porosity, and outstanding electrochemical performance. The dependence of electrochemical performance on structural, textural, and functional properties of carbons engineered by various synthesis strategies is investigated in detail. Moreover, the as-assembled symmetrical supercapacitor exhibits high energy density of 25.4 Wh kg-1 at a power density of 225 W kg-1 and retains 20.7 Wh kg-1 even at a very high power of 9000 W kg-1. This work provides an environmentally benign strategy and new insights to efficiently regulate the porosity of hierarchical porous carbons derived from biomass wastes for energy storage applications.

Unravelling RNA-substrate interactions in a ribozyme-catalysed reaction using fluorescent turn-on probes.

PubMed

Gaffarogullari, Ece Cazibe; Greulich, Peter; Kobitski, Andrei Yu; Nierth, Alexander; Nienhaus, G Ulrich; Jäschke, Andres

2015-04-07

The Diels-Alder reaction is one of the most important C-C bond-forming reactions in organic chemistry, and much effort has been devoted to controlling its enantio- and diastereoselectivity. The Diels-Alderase ribozyme (DAse) catalyses the reaction between anthracene dienes and maleimide dienophiles with multiple-turnover, stereoselectivity, and up to 1100-fold rate acceleration. Here, a new generation of anthracene-BODIPY-based fluorescent probes was developed to monitor catalysis by the DAse. The brightness of these probes increases up to 93-fold upon reaction with N-pentylmaleimide (NPM), making these useful tools for investigating the stereochemistry of the ribozyme-catalysed reaction. With these probes, we observed that the DAse catalyses the reaction with >91% de and >99% ee. The stereochemistry of the major product was determined unambiguously by rotating-frame nuclear Overhauser NMR spectroscopy (ROESY-NMR) and is in agreement with crystallographic structure information. The pronounced fluorescence change of the probes furthermore allowed a complete kinetic analysis, which revealed an ordered bi uni type reaction mechanism, with the dienophile binding first. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strychnine as Target, Samarium Diiodide as Tool: A Personal Story.

PubMed

Beemelmanns, Christine; Reissig, Hans-Ulrich

2015-10-01

Strychnine stands out from the group of classical natural products as one of the first complex compounds to be isolated in pure form and an extreme challenge to be structurally characterized. It has played a central role in natural product total syntheses and the surge in the development of innovative synthetic methods for many decades. Recently, we have accomplished one of the shortest formal total syntheses of strychnine (in ten steps and 14% overall yield or even shorter in eight steps and 10% overall yield). The evolution of a productive synthetic strategy, as well as the synthetic challenges tackled, are described here in detail, including examples of related transformations. The successful synthetic strategy was inspired by the premise that the core structure could be derived from simple aromatic indole precursors by a reductive SmI2 -induced ketyl-aryl coupling. Other key reactions included a diastereoselective reduction and a regioselective elimination protocol. Altogether one of the shortest syntheses of iso-strychnine and hence of strychnine was established. Copyright © 2015 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diastereoselective addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones

NASA Astrophysics Data System (ADS)

Uteuliyev, Maulen M.; Nguyen, Thien T.; Coltart, Don M.

2015-12-01

The α-alkylation of ketones and their derivatives by the addition of their corresponding enolates to alkyl halides is a fundamental synthetic transformation, but its utility is limited because the key bond-forming step proceeds in a bimolecular nucleophilic substitution fashion. Here we describe how an umpolung strategy that involves the addition of Grignard reagents to α-epoxy N-sulfonyl hydrazones—directed by the alkoxide of the 1-azo-3-alkoxy propenes formed in situ via base-induced ring opening of the epoxide—leads to the syn-selective production of α-alkyl-β-hydroxy N-sulfonyl hydrazones with α-quaternary centres. This transformation is remarkable in its ability to incorporate an unprecedented range of carbon-based substituents, which include primary, secondary and tertiary alkyl, as well as alkenyl, aryl, allenyl and alkynyl groups. Subsequent hydrolysis of the β-hydroxy N-sulfonyl hydrazone products produces the corresponding β-hydroxy ketones. In addition to hydrolysis, the hydrazone products are poised to undergo numerous different known synthetic transformations via well-established chemistry, which would provide access to a wide array of useful structures.

The Scaled-Up Synthesis of Nanostructured Ultra-High-Temperature Ceramics and Resistance Sintering of Tantalum Carbide Nanopowders and Composites

NASA Astrophysics Data System (ADS)

Kelly, James P.

Ultra-high temperature ceramics (UHTCs) are a unique class of materials with the potential to withstand harsh environments due to covalent bonding, which gives these materials high melting temperatures, although decomposition temperatures should also be considered. For example, the melting temperature of TaC is near 4000 K, but may vaporize at lower temperatures. The high melting temperatures also make them difficult to process without high pressures and temperatures and to achieve dense ceramics with a nanostructure. Such materials however are appealing for aerospace technologies. The ability to generate high density compacts and maintain a nanostructure could allow for unprecedented control and improvement to the mechanical properties. The goal of this work is to develop processes for the synthesis and consolidation of nanostructured UHTCs. A self-propagating solvothermal synthesis technique for making UHTC nanopowders is presented. The technique is fast, scalable, and requires minimal external energy input. Synthesis of transition metal boride, carbide, and nitride powders is demonstrated. TaC is synthesized using a range of synthesis conditions and characterized to determine the fundamental mechanisms controlling the nanopowder characteristics. Discussion on purification of the powders is also presented. The sintering of TaC nanopowders produced by the solvothermal synthesis method is performed by resistance sintering. The effects of temperature, heating rate, and dwell time on densification and grain growth is presented. Adequate powder processing, carbon content, volatilization, and additives are found to be critical factors affecting the densification, microstructure, and grain growth. The optimal range of carbon addition for minimizing oxygen content is determined. WC and ZrC are evaluated as additives for reducing grain growth of TaC. Secondary phases and/or solid solutions are capable of suppressing grain growth. A unified approach to solid solution chemistries to control the densification, microstructure, and properties of UHTCs in general is presented. This work has important consequences on advancing the properties of UHTCs.

Synthesis and binding studies of Alzheimer ligands on solid support.

PubMed

Rzepecki, Petra; Geib, Nina; Peifer, Manuel; Biesemeier, Frank; Schrader, Thomas

2007-05-11

Aminopyrazole derivatives constitute the first class of nonpeptidic rationally designed beta-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure form. Hexa- and octapeptide pendants with internal di- and tetrapeptide bridges are now amenable in high yields to combinatorial synthesis of compound libraries for high-throughput screening purposes. Solid-phase peptide synthesis (SPPS) on an acid-resistant PAM allows us, after PMB deprotection, to subject the free aminopyrazole binding sites in an immobilized state to on-bead assays with fluorescence-labeled peptides. From the fluorescence emission intensity decrease, individual binding constants can be calculated via reference curves by simple application of the law of mass action. Gratifyingly, host/guest complexation can be monitored quantitatively even for those ligands, which are almost insoluble in water.

Expanding the chemical toolbox for the synthesis of large and uniquely modified proteins

NASA Astrophysics Data System (ADS)

Bondalapati, Somasekhar; Jbara, Muhammad; Brik, Ashraf

2016-05-01

Methods to prepare proteins that include a specific modification at a desired position are essential for understanding their cellular functions and physical properties in living systems. Chemical protein synthesis, which relies on the chemoselective ligation of unprotected peptides, enables the preparation of modified proteins that are not easily fabricated by other methods. In contrast to recombinant approaches, chemical synthesis can be used to prepare protein analogues such as D-proteins, which are useful in protein structure determination and the discovery of novel therapeutics. Post-translationally modifying proteins is another example where chemical protein synthesis proved itself as a powerful approach for preparing samples with high homogeneity and in workable quantities. In this Review, we discuss the basic principles of the field, focusing on novel chemoselective peptide ligation approaches such as native chemical ligation and the recent advances based on this method with a proven record of success in the synthesis of highly important protein targets.

High-Yield Synthesis and Optical Properties of Carbon Nanotube Porins

DOE PAGES

Tunuguntla, Ramya H.; Chen, Xi; Belliveau, Allison; ...

2017-01-18

Carbon nanotube porins (CNTPs) are a convenient membrane-based model system for studying nanofluidic transport that replicates a number of key structural features of biological membrane channels. We present a generalized approach for CNTP synthesis using sonochemistry-assisted segmenting of carbon nanotubes. Prolonged tip sonication in the presence of lipid molecules debundles and fragments long carbon nanotube aggregates into stable and water-soluble individual CNTPs with lengths in the range 5–20 nm. We discuss the main parameters that determine the efficiency and the yield of this process, describe the optimized conditions for high-yield CNTP synthesis, and demonstrate that this methodology can be adaptedmore » for synthesis of CNTPs of different diameters. We also present the optical properties of CNTPs and show that a combination of Raman and UV–vis–NIR spectroscopy can be used to monitor the quality of the CNTP synthesis. Altogether, CNTPs represent a versatile nanopore building block for creating higher-order functional biomimetic materials.« less

Synthesis of New Organic Semiconducting Polymer Materials Having High Radiowave Absorption Rate

DTIC Science & Technology

2008-11-01

ISTC Project No. #1571P Synthesis of New Organic Semiconducting Polymer Materials Having High Radiowave Absorption Rate Final Project Technical...Technology Center ( ISTC ), Moscow. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information...polymer materials having high radiowave absorption rate 5a. CONTRACT NUMBER ISTC Registration No: A-1571p 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates - A Substudy.

PubMed

Hursel, Rick; Martens, Eveline A P; Gonnissen, Hanne K J; Hamer, Henrike M; Senden, Joan M G; van Loon, Luc J C; Westerterp-Plantenga, Margriet S

2015-01-01

Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620). In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake. Clinicaltrials.gov NCT01551238.

Prolonged Adaptation to a Low or High Protein Diet Does Not Modulate Basal Muscle Protein Synthesis Rates – A Substudy

PubMed Central

Hursel, Rick; Martens, Eveline A. P.; Gonnissen, Hanne K. J.; Hamer, Henrike M.; Senden, Joan M. G.; van Loon, Luc J. C.; Westerterp-Plantenga, Margriet S.

2015-01-01

Background Based on controlled 36 h experiments a higher dietary protein intake causes a positive protein balance and a negative fat balance. A positive net protein balance may support fat free mass accrual. However, few data are available on the impact of more prolonged changes in habitual protein intake on whole-body protein metabolism and basal muscle protein synthesis rates. Objective To assess changes in whole-body protein turnover and basal muscle protein synthesis rates following 12 weeks of adaptation to a low versus high dietary protein intake. Methods A randomized parallel study was performed in 40 subjects who followed either a high protein (2.4 g protein/kg/d) or low protein (0.4 g protein/kg/d) energy-balanced diet (30/35/35% or 5/60/35% energy from protein/carbohydrate/fat) for a period of 12 weeks. A subgroup of 7 men and 8 women (body mass index: 22.8±2.3 kg/m2, age: 24.3±4.9 y) were selected to evaluate the impact of prolonged adaptation to either a high or low protein intake on whole body protein metabolism and basal muscle protein synthesis rates. After the diet, subjects received continuous infusions with L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine in an overnight fasted state, with blood samples and muscle biopsies being collected to assess post-absorptive whole-body protein turnover and muscle protein synthesis rates in vivo in humans. Results After 12 weeks of intervention, whole-body protein balance in the fasted state was more negative in the high protein treatment when compared with the low protein treatment (-4.1±0.5 vs -2.7±0.6 μmol phenylalanine/kg/h;P<0.001). Whole-body protein breakdown (43.0±4.4 vs 37.8±3.8 μmol phenylalanine/kg/h;P<0.03), synthesis (38.9±4.2 vs 35.1±3.6 μmol phenylalanine/kg/h;P<0.01) and phenylalanine hydroxylation rates (4.1±0.6 vs 2.7±0.6 μmol phenylalanine/kg/h;P<0.001) were significantly higher in the high vs low protein group. Basal muscle protein synthesis rates were maintained on a low vs high protein diet (0.042±0.01 vs 0.045±0.01%/h;P = 0.620). Conclusions In the overnight fasted state, adaptation to a low-protein intake (0.4 g/kg/d) does not result in a more negative whole-body protein balance and does not lower basal muscle protein synthesis rates when compared to a high-protein intake. Trial Registration Clinicaltrials.gov NCT01551238. PMID:26367529

High power Nb-doped LiFePO4 Li-ion battery cathodes; pilot-scale synthesis and electrochemical properties

NASA Astrophysics Data System (ADS)

Johnson, Ian D.; Blagovidova, Ekaterina; Dingwall, Paul A.; Brett, Dan J. L.; Shearing, Paul R.; Darr, Jawwad A.

2016-09-01

High power, phase-pure Nb-doped LiFePO4 (LFP) nanoparticles are synthesised using a pilot-scale continuous hydrothermal flow synthesis process (production rate of 6 kg per day) in the range 0.01-2.00 at% Nb with respect to total transition metal content. EDS analysis suggests that Nb is homogeneously distributed throughout the structure. The addition of fructose as a reagent in the hydrothermal flow process, followed by a post synthesis heat-treatment, affords a continuous graphitic carbon coating on the particle surfaces. Electrochemical testing reveals that cycling performance improves with increasing dopant concentration, up to a maximum of 1.0 at% Nb, for which point a specific capacity of 110 mAh g-1 is obtained at 10 C (6 min for the charge or discharge). This is an excellent result for a high power cathode LFP based material, particularly when considering the synthesis was performed on a large pilot-scale apparatus.

Towards Stable CuZnAl Slurry Catalysts for the Synthesis of Ethanol from Syngas

NASA Astrophysics Data System (ADS)

Dong, Weibing; Gao, Zhihua; Zhang, Qian; Huang, Wei

2018-07-01

A stable CuZnAl slurry catalyst for the synthesis of ethanol from syngas has been developed by adjusting the heat treatment conditions of the complete liquid-phase method. The activity evaluation results showed that the CuZnAl catalyst, when heat-treated under a high pressure and temperature, was a stable catalyst for the synthesis of ethanol. The selectivity of ethanol using the CuZnAl slurry catalyst, which was heat-treated at 553 K under 4.0 MPa, increased continuously with time and was stable at approximately 26.00% after 144 h. The characterization results indicated that the CuZnAl slurry catalyst heat-treated under high pressure conditions could facilitate the formation of a more perfect structure with a larger specific surface area. The prepared catalyst contained a balance of strong and weak acid sites, an appropriate form of Cu2O and a high Cu/Zn atomic ratio at the catalyst surface, providing its stability in ethanol synthesis from syngas.