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Sample records for enantioselective oxidative dearomatization

  1. Intermolecular enantioselective dearomatization reaction of β-naphthol using meso-aziridine: a bifunctional in situ generated magnesium catalyst.

    PubMed

    Yang, Dongxu; Wang, Linqing; Han, Fengxia; Li, Dan; Zhao, Depeng; Wang, Rui

    2015-02-01

    A direct, facile, and highly diastereo- and enantioselective dearomatization reaction of β-naphthol derivatives with aziridines has been developed for the first time. A newly designed Box-OH ligand was employed for an in situ generated magnesium catalyst and proved to be efficient. The corresponding dearomatization product was transformed into a polycyclic scaffold and polyhydroxylated compound. (1) H NMR studies revealed the activation mode of the dearomatization process of β-naphthols, and a clear positive nonlinear effect was observed in the reaction, and provides insight into the coordination environment around the Mg(II) center and the possible active species. PMID:25589219

  2. Evolution of an Oxidative Dearomatization Enabled Total Synthesis of Vinigrol

    PubMed Central

    Yang, Qingliang; Draghici, Cristian; Li, Fang; Smith, Brandon R.; Das, Pradipta

    2014-01-01

    The evolution of the synthetic strategy resulting in a total synthesis of vinigrol is presented. Oxidative dearomatization/intramolecular Diels-Alder cycloaddition has served as the successful cornerstone for all of the approaches. Extensive radical cyclization efforts to form the tetracyclic core resulted in interesting and surprising reaction outcomes, none of which could be advanced to vinigrol. These cyclization obstacles were successfully overcome by using Heck instead of radical cyclizations. The total synthesis features a trifluoroethyl ether protecting group being used for the first time in organic synthesis. The logic of its selection and the group’s importance beyond protecting the C8a hydroxyl group is presented along with a discussion of strategies for its removal. Because of the compact tetracyclic cage the route is built around many unusual reaction observations and solutions have emerged. For example, a first of its kind Grob fragmentation reaction featuring a trifluoroethyl leaving group has been uncovered, interesting interrupted selenium dioxide allylic oxidations have been observed as well as intriguing catalyst and counterion dependent directed hydrogenations. PMID:24258093

  3. Enantioselective oxidative boron Heck reactions.

    PubMed

    Lee, A-L

    2016-06-28

    This review highlights the use of the oxidative boron Heck reaction in enantioselective Heck-type couplings. The enantioselective oxidative boron Heck reaction overcomes several limitations of the traditional Pd(0)-catalysed Heck coupling and has subsequently allowed for intermolecular couplings of challenging systems such as cyclic enones, acyclic alkenes, and even site selectively on remote alkenes. PMID:26529247

  4. Dearomatization through Halofunctionalization Reactions.

    PubMed

    Liang, Xiao-Wei; Zheng, Chao; You, Shu-Li

    2016-08-16

    Recent advances in dearomatization through halofunctionalization reactions are summarized in this Minireview. Two general categories of strategies are currently employed in this field. On one hand, the reaction can be initiated with electrophilic halogenation at an alkyne or alkene moiety. The resulting halonium ion intermediate is then captured by a pendant aromatic ring at the ipso position, affording the dearomatization product. On the other hand, electrophilic halogenation can directly take place at a substituted arene, and the final dearomatization product is furnished by deprotonation or intramolecular nucleophilic trap. Highly enantioselective variants have been realized in the latter case by organocatalysis or transition metal catalysis. By applying these methods, various valuable halogenated polycyclic molecular architectures have been obtained from readily available starting materials. PMID:27377184

  5. Dearomatization Reactions Using Phthaloyl Peroxide.

    PubMed

    Eliasen, Anders M; Christy, Mitchell; Claussen, Karin R; Besandre, Ronald; Thedford, Randal P; Siegel, Dionicio

    2015-09-18

    A new oxidative dearomatization reaction has been developed using phthaloyl peroxide to chemoselectively install two oxygen-carbon bonds into aromatic precursors. The oxidation reaction proceeds only once; addition of superstoichiometric equivalents of phthaloyl peroxide does not react further with the newly generated 1,3-cyclohexadiene. The reaction has been challenged by the addition of different functional groups and shown to maintain chemoselectivity. Due to the broad reactivity with 1,2-methylenedioxybenzene derivatives, linear free energy correlations were determined and support a mechanism proceeding through diradicals analogous to arene-hydroxylation reactions using phthaloyl peroxide. PMID:26333308

  6. Palladium(0)-Catalyzed Intermolecular Allylic Dearomatization of Indoles by a Formal [4+2] Cycloaddition Reaction.

    PubMed

    Gao, Run-Duo; Xu, Qing-Long; Zhang, Bo; Gu, Yiting; Dai, Li-Xin; You, Shu-Li

    2016-08-01

    Bridged indoline derivatives were synthesized by an intermolecular Pd-catalyzed allylic dearomatization reaction of substituted indoles. The reaction between indoles and allyl carbonates bearing a nucleophilic alcohol side-chain proceeds in a cascade fashion, providing bridged indolines in excellent enantioselectivity. PMID:27321285

  7. Short, Enantioselective Total Synthesis of Highly Oxidized Taxanes.

    PubMed

    Yuan, Changxia; Jin, Yehua; Wilde, Nathan C; Baran, Phil S

    2016-07-11

    In the realm of natural product chemistry, few isolates have risen to the level of fame justifiably accorded to Taxol (1) and its chemical siblings. This report describes the most concise route to date for accessing the highly oxidized members of this family. As representative members of taxanes containing five oxygen atoms, decinnamoyltaxinine E (2) and taxabaccatin III (3), have succumbed to enantioselective total synthesis for the first time in only 18 steps from a simple olefin starting material. The strategy holistically mimics nature's approach (two-phase synthesis) and features a carefully choreographed sequence of stereoselective oxidations and a remarkable redox-isomerization to set the key trans-diol present in 2 and 3. This work lays the critical groundwork necessary to access even higher oxidized taxanes such as 1 in a more practical fashion, thus empowering a medicinal chemistry campaign that is not wedded to semi-synthesis. PMID:27240325

  8. Palladium(II)/Brønsted Acid-Catalyzed Enantioselective Oxidative Carbocyclization-Borylation of Enallenes.

    PubMed

    Jiang, Tuo; Bartholomeyzik, Teresa; Mazuela, Javier; Willersinn, Jochen; Bäckvall, Jan-E

    2015-05-11

    An enantioselective oxidative carbocyclization-borylation of enallenes that is catalyzed by palladium(II) and a Brønsted acid was developed. Biphenol-type chiral phosphoric acids were superior co-catalysts for inducing the enantioselective cyclization. A number of chiral borylated carbocycles were synthesized in high enantiomeric excess. PMID:25808996

  9. Palladium(II)/Brønsted Acid-Catalyzed Enantioselective Oxidative Carbocyclization–Borylation of Enallenes**

    PubMed Central

    Jiang, Tuo; Bartholomeyzik, Teresa; Mazuela, Javier; Willersinn, Jochen; Bäckvall, Jan-E

    2015-01-01

    An enantioselective oxidative carbocyclization–borylation of enallenes that is catalyzed by palladium(II) and a Brønsted acid was developed. Biphenol-type chiral phosphoric acids were superior co-catalysts for inducing the enantioselective cyclization. A number of chiral borylated carbocycles were synthesized in high enantiomeric excess. PMID:25808996

  10. Chiral Brønsted Acid Catalyzed Enantioselective Phosphonylation of Allylamine via Oxidative Dehydrogenation Coupling.

    PubMed

    Cheng, Ming-Xing; Ma, Ran-Song; Yang, Qiang; Yang, Shang-Dong

    2016-07-01

    A new strategy for the synthesis of chiral α-amino phosphonates by enantioselective C-H phosphonylation of allylamine with phosphite in the presence of a chiral Brønsted acid catalyst has been developed. This protocol successfully integrates direct C-H oxidation with asymmetric phosphonylation and exhibits high enantioselectivity. PMID:27331612

  11. o-Quinone Methides via Oxone-Mediated Benzofuran Oxidative Dearomatization and Their Intramolecular Cycloaddition with Carbonyl Groups: An Expeditious Construction of the Central Tetracyclic Core of Integrastatins, Epicoccolide A, and Epicocconigrone A.

    PubMed

    More, Atul A; Ramana, Chepuri V

    2016-02-01

    The intramolecular cycloaddition of o-quinone methides (o-QMs) with a carbonyl group has been envisaged and executed successfully in the context of constructing the complex and rare [6,6,6,6]-tetracyclic core found in the integrastatins, epicoccolide A, and epicocconigrone A. These transient o-QMs were generated easily from the oxidative dearomatization of the corresponding C2-(aryl)benzofuran by employing Oxone in acetone-water at rt. The subsequent cycloaddition with the carbonyl (or conjugated olefin) present on the C2-aryl group was spontaneous. PMID:26815222

  12. Enantioselective Synthesis of Indole-Annulated Medium-Sized Rings.

    PubMed

    Huang, Lin; Dai, Li-Xin; You, Shu-Li

    2016-05-11

    Asymmetric synthesis of indole-annulated medium-sized-ring compounds is developed through an iridium-catalyzed allylic dearomatization/retro-Mannich/hydrolysis cascade reaction. The reaction features mild conditions and a broad substrate scope. Under the optimal conditions, various seven-, eight-, or nine-membered-ring compounds can be afforded in good to excellent yields and excellent enantioselectivity. The proposed mechanism is supported by capturing the dearomatized intermediate through in situ reduction. PMID:27093370

  13. Mg(II) -Mediated Catalytic Asymmetric Dearomatization (CADA) Reaction of β-Naphthols with Dialkyl Acetylenedicarboxylates.

    PubMed

    Wang, Linqing; Yang, Dongxu; Li, Dan; Wang, Pengxin; Wang, Kezhou; Wang, Jie; Jiang, Xianxing; Wang, Rui

    2016-06-13

    A Mg(II) -mediated catalytic asymmetric dearomatization (CADA) reaction of β-naphthols has been developed. The reaction proceeds under ambient temperature and give a series of chiral trisubstituted olefins with good chemoselectivities, Z/E ratios, and excellent enantioselectivities. A fluorinated β-naphthol was designed to generate chiral organofluorine skeletons through the current CADA reaction. Moreover, an interesting tandem cyclization reaction was observed in the following transformation process through an undiscovered intramolecular hydride transfer pathway. PMID:27139904

  14. Mechanism and Selectivity of Ru(II) - and Rh(III) -Catalyzed Oxidative Spiroannulation of Naphthols and Phenols with Alkynes through a C-H Activation/Dearomatization Strategy.

    PubMed

    Zhang, Mei; Huang, Genping

    2016-06-27

    The ruthenium- and rhodium-catalyzed oxidative spiroannulation of naphthols and phenols with alkynes was investigated by means of density functional theory calculations. The results show that the reaction undergoes O-H deprotonation/C(sp(2) )-H bond cleavage through a concerted metalation-deprotonation mechanism/migratory insertion of the alkyne into the M-C bond to deliver the eight-membered metallacycle. However, the dearomatization through the originally proposed enol-keto tautomerization/C-C reductive elimination was calculated to be kinetically inaccessible. Alternatively, an unusual metallacyclopropene, generated from the isomerization of the eight-membered metallacycle through rotation of the C-C double bond, was identified as a key intermediate to account for the experimental results. The subsequent C-C coupling between the carbene carbon atom and the carbon atom of the 2-naphthol/phenol ring was calculated to be relatively facile, leading to the formation of the unexpected dearomatized products. The calculations reproduce quite well the experimentally observed formal [5+2] cycloaddition in the rhodium-catalyzed oxidative annulation of 2-vinylphenols with alkynes. The calculations show that compared with the case of 2-alkenylphenols, the presence of conjugation effects and less steric repulsion between the phenol ring and the vinyl moiety make the competing reductive oxyl migration become dominant, which enables the selectivity switch from the spiroannulation to the formal [5+2] cycloaddition. PMID:27225930

  15. Oxidative Dearomatization of 4,5,6,7-Tetrahydro-1H-indoles Obtained by Metal- and Solvent-Free Thermal 5-endo-dig Cyclization: The Route to Erythrina and Lycorine Alkaloids.

    PubMed

    Andreev, Ivan A; Ratmanova, Nina K; Novoselov, Anton M; Belov, Dmitry S; Seregina, Irina F; Kurkin, Alexander V

    2016-05-17

    A facile one-pot approach based on a thermally induced metal- and solvent-free 5-endo-dig cyclization reaction of the amino propargylic alcohols in combination with Dess-Martin periodinane-promoted oxidative dearomatization of 4,5,6,7-tetrahydroindole intermediates provides an efficient and robust access to 5,6-dihydro-1H-indol-2(4H)ones. Green, relatively mild and operationally simple characteristics of the synthetic sequence are the major advantages, which greatly amplify the developed methodology. The utility of obtained indolones as unified key precursors is demonstrated by the application of these products to the formal total syntheses of a whole pleiad of Erythrina- and Lycorine-type alkaloids, namely (±)-erysotramidine, (±)-erysotrine, (±)-erythravine, (±)-γ-lycorane, and abnormal erythrinanes (±)-coccoline and (±)-coccuvinine. PMID:27076115

  16. Perylenequinone Natural Products: Enantioselective Synthesis of the Oxidized Pentacyclic Core‡

    PubMed Central

    Mulrooney, Carol A.; Morgan, Barbara J.; Li, Xiaolin; Kozlowski, Marisa C.

    2009-01-01

    An enantioselective approach to the perylenequinone core found in the mold perylenequinone natural products is outlined. Specifically, the first asymmetric syntheses of helical chiral perylenequinones absent any additional stereogenic centers are described. Key elements of the synthetic venture include a catalytic enantioselective biaryl coupling, a PIFA-induced naphthalene hydroxylation, and a palladium-mediated aromatic decarboxylation. Transfer of the binaphthalene axial stereochemistry to the perylenequinone helical stereochemistry proceeded with good fidelity. Furthermore, the resultant perylenequinones were shown to possess sufficient atropisomeric stability to be viable intermediates in the biogenesis of the perylenequinone natural products. This stability supports the use of the helical axis as a stereochemical relay in synthesis of the natural products containing additional stereochemical centers. PMID:19894746

  17. Development of Enantioselective Polyclonal Antibodies to Detect Styrene Oxide Protein Adducts

    PubMed Central

    Shen, Shuijie; Zhang, Fan; Zeng, Su; Tian, Ye; Chai, Xiaojuan; Gee, Shirley; Hammock, Bruce D.; Zheng, Jiang

    2012-01-01

    Styrene has been reported to be pneumotoxic and hepatotoxic in humans and animals. Styrene oxide, a major reactive metabolite of styrene, has been found to form covalent binding with proteins, such as albumin and hemoglobin. Styrene oxide has two optical isomers and it was reported that the (R)-enantiomer was more toxic than the (S)-enantiomer. The purpose of this study was to develop polyclonal antibodies that can stereoselectively recognize proteins modified by styrene oxide enantiomers at cysteine residues. Immunogens were prepared by alkylation of thiolated keyhole limpet hemocyanin (KLH) with styrene oxide enantiomers. Polyclonal antibodies were raised by immunization of rabbits with the chiral immunogens. Titration tests showed all six rabbits generated high titers of antisera that recognize (R)- or (S)-coating antigens accordingly. No cross-reaction was observed toward the carrier protein (BSA). All three rabbits immunized with (R)-immunogen produced antibodies that show enantioselectivity to the corresponding antigen, while only one among the three rabbits immunized with (S)-immunogen generated antibodies with enantioselectivity of the recognition. The enantioselectivity was also observed in competitive ELISA and immunoblot analysis. Additionally, competitive ELISA tests showed that the immunorecognition required the hydroxyl group of the haptens. Immunoblot analysis demonstrated that the immunorecognition depended on the amount of protein adducts blotted and hapten loading in protein adducts. In summary, we successfully developed polyclonal antibodies to stereoselectively detect protein adducts modified by styrene oxide enantiomers. PMID:19245253

  18. Copper(I)-Catalyzed Asymmetric Dearomatization of Indole Acetamides with 3-Indolylphenyliodonium Salts.

    PubMed

    Liu, Chuan; Yi, Ji-Cheng; Liang, Xiao-Wei; Xu, Ren-Qi; Dai, Li-Xin; You, Shu-Li

    2016-07-25

    The rapid and direct asymmetric synthesis of 3-(3a-indolyl)hexahydropyrroloindoline motifs is an extremely important part of the total synthesis of several alkaloid structures. Herein, an intermolecular, asymmetric cascade dearomatization reaction of indole acetamides with 3-indolylphenyliodonium salts has been developed. This protocol provides a straightforward access to 3-(3a-indolyl)hexahydropyrroloindolines bearing an all-carbon quaternary stereocenter at the C3 position of the indoline ring with high enantioselectivities. The utility of the protocol has been demonstrated by the formal asymmetric synthesis of folicanthine. PMID:27171171

  19. Highly enantioselective oxidative couplings of 2-naphthols catalyzed by chiral bimetallic oxovanadium complexes with either oxygen or air as oxidant.

    PubMed

    Guo, Qi-Xiang; Wu, Zhi-Jun; Luo, Zhi-Bin; Liu, Quan-Zhong; Ye, Jian-Liang; Luo, Shi-Wei; Cun, Lin-Feng; Gong, Liu-Zhu

    2007-11-14

    The chiral bimetallic oxovanadium complexes have been designed for the enantioselective oxidative coupling of 2-naphthols bearing various substituents at C6 and/or C7. The chirality transferring from the amino acid to the axis of the biphenyl in oxovanadium complexes 2 was found to occur with the use of UV and CD spectra and DFT calculation. The homo-coupling reaction with oxygen as the oxidant was promoted by 5 mol % of an oxovanadium complex derived from L-isoleucine and achiral biphenol to afford binaphthols in nearly quantitative yields with high enantioselectivities of up to 98% ee. An oxovanadium complex derived from L-isoleucine and H8-binaphthol is highly efficient at catalyzing the air-oxidized coupling of 2-naphthols with excellent enantioselectivities of up to 97% ee. 51V NMR study shows that the oxovanadium complexes have two vanadium(V) species. Kinetic studies, the cross-coupling reaction, and HRMS spectral studies on the reaction have been carried out and illustrate that two vanadium(V) species are both involved in catalysis and that the coupling reaction undergoes a radical-radical mechanism in an intramolecular manner. Quantum mechanical calculations rationalize the importance of the cooperative effects of the axial chirality matching S-amino acids on the stereocontrol of the oxidative coupling reaction. The application of the transformation in the preparation of chiral ligands and conjugated polymers confirms the importance of the current process in organic synthesis. PMID:17956093

  20. Enantioselective Oxidative Rearrangements with Chiral Hypervalent Iodine Reagents

    PubMed Central

    Brown, Michael; Kumar, Ravi; Rehbein, Julia

    2016-01-01

    Abstract A stereoselective hypervalent iodine‐promoted oxidative rearrangement of 1,1‐disubstituted alkenes has been developed. This practically simple protocol provides access to enantioenriched α‐arylated ketones without the use of transition metals from readily accessible alkenes. PMID:26800241

  1. Enantioselective Oxidative Rearrangements with Chiral Hypervalent Iodine Reagents.

    PubMed

    Brown, Michael; Kumar, Ravi; Rehbein, Julia; Wirth, Thomas

    2016-03-14

    A stereoselective hypervalent iodine-promoted oxidative rearrangement of 1,1-disubstituted alkenes has been developed. This practically simple protocol provides access to enantioenriched α-arylated ketones without the use of transition metals from readily accessible alkenes. PMID:26800241

  2. Decarboxylative dearomatization and mono-α-arylation of ketones.

    PubMed

    Mendis, Shehani N; Tunge, Jon A

    2016-06-01

    We report the first example of a palladium-catalyzed decarboxylative dearomatization reaction that occurs via Pd-π-benzyl intermediates. In fact, the Pd-catalyzed decarboxylative cross-coupling reaction of benzyl enol carbonates can lead to either the dearomatized alicyclic ketones or α-monoarylated ketone products depending on the catalyst and ligand employed. PMID:27229656

  3. Enantioselective N-heterocyclic carbene-catalyzed Michael addition to α,β-unsaturated aldehydes by redox oxidation.

    PubMed

    Rong, Zi-Qiang; Jia, Min-Qiang; You, Shu-Li

    2011-08-01

    Enantioselective N-heterocyclic carbene-catalyzed Michael addition reactions to α,β-unsaturated aldehydes by redox oxidation were realized. With 10 mol % of camphor-derived triazolium salt D, 15 mol % of DBU, 5 mol % of NaBF(4), and 100 mol % of quinone oxidant, the reactions of various dicarbonyl compounds with α,β-unsaturated aldehydes led to 3,4-dihydro-α-pyrones in good yields and excellent ee's. PMID:21732659

  4. Enantioselective Allylic C-H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis.

    PubMed

    Ammann, Stephen E; Liu, Wei; White, M Christina

    2016-08-01

    The enantioselective synthesis of isochroman motifs has been accomplished by palladium(II)-catalyzed allylic C-H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide-oxazoline (ArSOX) ligand. The allylic C-H oxidation reaction proceeds with the broadest scope and highest levels of asymmetric induction reported to date (avg. 92 % ee, 13 examples with greater than 90 % ee). PMID:27376625

  5. Iridium-catalyzed anti-diastereo- and enantioselective carbonyl (trimethylsilyl)allylation from the alcohol or aldehyde oxidation level.

    PubMed

    Han, Soo Bong; Gao, Xin; Krische, Michael J

    2010-07-01

    Using the ortho-cyclometalated pi-allyl iridium precatalyst (R)-I derived from [Ir(cod)Cl](2), 4-cyano-3-nitrobenzoic acid, (R)-SEGPHOS, and allyl acetate, enantioselective transfer hydrogenation of alpha-(trimethylsilyl)allyl acetate in the presence of aldehydes 2a-i mediated by 2-propanol delivers products of (trimethylsilyl)allylation 4a-i in good isolated yields and with exceptional levels of anti-diastereoselectivity and enantioselectivity (90-99% ee). In the absence of 2-propanol, but under otherwise identical reaction conditions, carbonyl (trimethylsilyl)allylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts 4a-i with roughly equivalent isolated yields and stereoselectivities. To evaluate the synthetic utility of the reaction products 4a-i, adduct 4g was converted to the 1,4-ene-diol 5g via dioxirane-mediated oxidative desilylation with allylic transposition, the allylic alcohol 6g via protodesilylation with allylic transposition, and the gamma-lactam 7g via chlorosulfonyl isocyanate-mediated cycloaddition. PMID:20540509

  6. Enantioselective Protonation

    PubMed Central

    Mohr, Justin T.; Hong, Allen Y.; Stoltz, Brian M.

    2010-01-01

    Enantioselective protonation is a common process in biosynthetic sequences. The decarboxylase and esterase enzymes that effect this valuable transformation are able to control both the steric environment around the proton acceptor (typically an enolate) and the proton donor (typically a thiol). Recently, several chemical methods to achieve enantioselective protonation have been developed by exploiting various means of enantiocontrol in different mechanisms. These laboratory transformations have proven useful for the preparation of a number of valuable organic compounds. PMID:20428461

  7. Copper-catalyzed intermolecular asymmetric propargylic dearomatization of indoles.

    PubMed

    Shao, Wen; Li, He; Liu, Chuan; Liu, Chen-Jiang; You, Shu-Li

    2015-06-22

    The first copper-catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee. PMID:25968474

  8. Chiral N-salicylidene vanadyl carboxylate-catalyzed enantioselective aerobic oxidation of α-hydroxy esters and amides

    PubMed Central

    Weng, Shiue-Shien; Shen, Mei-Wen; Kao, Jun-Qi; Munot, Yogesh S.; Chen, Chien-Tien

    2006-01-01

    A series of chiral vanadyl carboxylates derived from N-salicylidene-l-α-amino acids and vanadyl sulfate has been developed. These configurationally well defined complexes were examined for the kinetic resolution of double- and mono-activated 2° alcohols. The best chiral templates involve the combination of l-tert-leucine and 3,5-di-t-butyl-, 3,5-diphenyl-, or 3,4-dibromo-salicylaldehyde. The resulting vanadyl(V)-methoxide complexes after recrystallization from air-saturated methanol serve as highly enantioselective catalysts for asymmetric aerobic oxidation of α-hydroxyl-esters and amides with a diverse array of α-, O-, and N-substituents at ambient temperature in toluene. The asymmetric inductions of the oxidation process are in the range of 10 to >100 in terms of selectivity factors (krel) in most instances. The previously undescribed aerobic oxidation protocol is also applicable to the kinetic resolution of C-13 taxol side chain with high selectivity factor (krel = 35). X-ray crystallographic analysis of an adduct between a given vanadyl complex and N-benzyl-mandelamide allows for probing the stereochemical origin of the nearly exclusive asymmetric control in the oxidation process. PMID:16501046

  9. Construction of erythrinane skeleton via Pd(0)-catalyzed intramolecular dearomatization of para-aminophenols.

    PubMed

    Xu, Ren-Qi; Gu, Qing; Wu, Wen-Ting; Zhao, Zhuo-An; You, Shu-Li

    2014-11-01

    A novel Pd(0)-catalyzed intramolecular arylative dearomatization of para-aminophenol derivatives is described. In the presence of 1.25 mol % [Pd(C3H5)Cl]2 and 3.75 mol % RuPhos, the arylative dearomatization reaction proceeds smoothly for a broad range of substrates, offering an efficient synthetic route to erythrinane derivatives in excellent yields. PMID:25308898

  10. Highly Chemo- and Regioselective Construction of Spirocarbocycles by a Pd(0)-Catalyzed Dearomatization of Phenol-Based Biaryls with 1,3-Dienes.

    PubMed

    Luo, Lei; Zheng, Huayu; Liu, Jingjing; Wang, Hui; Wang, Yaoyu; Luan, Xinjun

    2016-05-01

    A novel Pd(0)-catalyzed intermolecular carbocyclization of phenol-derived biaryls with 1,3-dienes has been implemented through a sequence of oxidative addition to the C-I bond, regioselective olefin insertion, and allylative dearomatization. This method provides a broad range of attractive spirocyclic compounds bearing two contiguous tertiary/quaternary carbon centers in good yields with excellent chemoselectivity and regioselectivity. Moreover, preliminary results indicate that asymmetric control of this process is feasible with chiral ligands. PMID:27120015

  11. Enhanced catalysis and enantioselective resolution of racemic naproxen methyl ester by lipase encapsulated within iron oxide nanoparticles coated with calix[8]arene valeric acid complexes.

    PubMed

    Sayin, Serkan; Akoz, Enise; Yilmaz, Mustafa

    2014-09-14

    In this study, two types of nanoparticles have been used as additives for the encapsulation of Candida rugosa lipase via the sol-gel method. In one case, the nanoparticles were covalently linked with a new synthesized calix[8]arene octa valeric acid derivative (C[8]-C4-COOH) to produce new calix[8]arene-adorned magnetite nanoparticles (NP-C[8]-C4-COOH), and then NP-C[8]-C4-COOH was used as an additive in the sol-gel encapsulation process. In the other case, iron oxide nanoparticles were directly added into the sol-gel encapsulation process in order to interact electrostatically with both C[8]-C4-COOH and Candida rugosa lipase. The catalytic activities and enantioselectivities of two novel encapsulated lipases (Enc-NP-C[8]-C4-COOH and Enc-C[8]-C4-COOH@Fe3O4) in the hydrolysis reaction of racemic naproxen methyl ester were evaluated. The results showed that the activity and enantioselectivity of the lipase were improved when the lipase was encapsulated in the presence of calixarene-based additives. Indeed, the encapsulated lipases have an excellent rate of enantioselectivity, with E = 371 and 265, respectively, as compared to the free enzyme (E = 137). The lipases encapsulated with C[8]-C4-COOH and iron oxide nanoparticles (Enc-C[8]-C4-COOH@Fe3O4) retained more than 86% of their initial activities after 5 repeated uses and 92% with NP-C[8]-C4-COOH. PMID:25012138

  12. Enantioselective Oxidation of Alkenes with Potassium Permanganate Catalyzed by Chiral Dicationic Bisguanidinium.

    PubMed

    Wang, Chao; Zong, Lili; Tan, Choon-Hong

    2015-08-26

    Chiral anion-controlled ion-pairing catalysis was demonstrated to be a wide-ranging strategy that can utilize a variety of cationic metal species. In a similar manner, we envision a complementary strategy using chiral cation in partnership with inorganic anionic metal salts. Herein, we report a chiral dicationic bisguanidinium-catalyzed asymmetric oxidation reaction of alkenes with potassium permanganate. Chiral induction is attributed to ion-pairing interaction between chiral cation and enolate anion. The success of the current permanganate oxidation reaction together with mechanistic insights should provide inspiration for expansion to other anionic metal salts and would open up new paradigms for asymmetric transition metal catalysis, phase-transfer catalysis, and ion-pairing catalysis. PMID:26237178

  13. Merger of visible light induced oxidation and enantioselective alkylation with a chiral iridium catalyst.

    PubMed

    Wang, Chuanyong; Zheng, Yu; Huo, Haohua; Röse, Philipp; Zhang, Lilu; Harms, Klaus; Hilt, Gerhard; Meggers, Eric

    2015-05-11

    A single chiral octahedral iridium(III) complex is used for visible light activated asymmetric photoredox catalysis. In the presence of a conventional household lamp and under an atmosphere of air, the oxidative coupling of 2-acyl-1-phenylimidazoles with N,N-diaryl-N-(trimethylsilyl)methylamines provides aminoalkylated products in 61-93 % yields with high enantiomeric excess (90-98 % ee). Notably, the iridium center simultaneously serves three distinct functions: as the exclusive source of chirality, as the catalytically active Lewis acid, and as a central part of the photoredox sensitizer. This conceptionally simple reaction Scheme may provide new avenues for the green synthesis of non-racemic chiral molecules. PMID:25832794

  14. Highly Enantioselective Iron-Catalyzed cis-Dihydroxylation of Alkenes with Hydrogen Peroxide Oxidant via an Fe(III) -OOH Reactive Intermediate.

    PubMed

    Zang, Chao; Liu, Yungen; Xu, Zhen-Jiang; Tse, Chun-Wai; Guan, Xiangguo; Wei, Jinhu; Huang, Jie-Sheng; Che, Chi-Ming

    2016-08-22

    The development of environmentally benign catalysts for highly enantioselective asymmetric cis-dihydroxylation (AD) of alkenes with broad substrate scope remains a challenge. By employing [Fe(II) (L)(OTf)2 ] (L=N,N'-dimethyl-N,N'-bis(2-methyl-8-quinolyl)-cyclohexane-1,2-diamine) as a catalyst, cis-diols in up to 99.8 % ee with 85 % isolated yield have been achieved in AD of alkenes with H2 O2 as an oxidant and alkenes in a limiting amount. This "[Fe(II) (L)(OTf)2 ]+H2 O2 " method is applicable to both (E)-alkenes and terminal alkenes (24 examples >80 % ee, up to 1 g scale). Mechanistic studies, including (18) O-labeling, UV/Vis, EPR, ESI-MS analyses, and DFT calculations lend evidence for the involvement of chiral Fe(III) -OOH active species in enantioselective formation of the two C-O bonds. PMID:27457506

  15. 2,2',3,3',6,6'-Hexachlorobiphenyl (PCB 136) is Enantioselectively Oxidized to Hydroxylated Metabolites by Rat Liver Microsomes

    PubMed Central

    Wu, Xianai; Pramanik, Ananya; Duffel, Michael W.; Hrycay, Eugene G.; Bandiera, Stelvio M.; Lehmler, Hans-Joachim; Kania-Korwel, Izabela

    2011-01-01

    Developmental exposure to multiple-ortho substituted polychlorinated biphenyls (PCBs) causes adverse neurodevelopmental outcomes in laboratory animals and humans by mechanisms involving the sensitization of Ryanodine receptors (RyRs). In the case of PCB 136, the sensitization of RyR is enantiospecific, with only (-)-PCB 136 being active. However, the role of enantioselective metabolism in the developmental neurotoxicity of PCB 136 is poorly understood. The present study employed hepatic microsomes from phenobarbital (PB-), dexamethasone (DEX-) and corn oil (VEH-)treated male Sprague-Dawley rats to investigate the hypothesis that PCB 136 atropisomers are enantioselectively metabolized by P450 enzymes to potentially neurotoxic, hydroxylated PCB 136 metabolites. The results demonstrated the time- and isoform-dependent formation of three metabolites, with 5-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol) being the major metabolite. The formation of 5-OH-PCB 136 increased with the activity of P450 2B enzymes in the microsomal preparation, which is consistent with PCB 136 metabolism by rat P450 2B1. The minor metabolite 4-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-4-ol) was produced by a currently unidentified P450 enzymes. An enantiomeric enrichment of (-)-PCB 136 was observed in microsomal incubations due to the preferential metabolism of (+)-PCB 136 to the corresponding 5-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol) atropisomer. 4-OH-PCB 136 displayed an enrichment of the atropisomer formed from (-)-PCB 136; however, the enrichment of this metabolite atropisomer didn't affect the enantiomeric enrichment of the parent PCB because 4-OH-PCB 136 is only a minor metabolite. Although the formation of 5- and 4-OH-PCB 136 atropisomers increased with time, the enantioselective formation of the OH-PCB metabolites resulted in constant enantiomeric enrichment, especially at later incubation times. These observations not only demonstrate that the chiral signatures of

  16. Switchable selectivity in an NHC-catalysed dearomatizing annulation reaction

    NASA Astrophysics Data System (ADS)

    Guo, Chang; Fleige, Mirco; Janssen-Müller, Daniel; Daniliuc, Constantin G.; Glorius, Frank

    2015-10-01

    The development of general catalytic methods for the regio- and stereoselective construction of chiral N-heterocycles in a diversity-oriented fashion remains a formidable challenge in organic synthesis. N-heterocyclic carbene (NHC) catalysis has been shown to produce a variety of outcomes, but control of the reactivity has rarely been demonstrated. Here we report a switchable catalytic activation of enals with aromatic azomethine imines that provides high selectivity using NHC organocatalysts. The original selectivity corresponds to the acidity of the base used in the reaction. The catalytically generated chiral homoenolate or enol intermediate undergoes enantioselective annulation with electrophiles such as N-iminoquinolinium ylides, N-iminoisoquinolinium ylides and β-N-iminocarboline ylides. The good-to-high overall yields, high regioselectivities and excellent enantioselectivities observed are controlled by the catalyst and reaction conditions.

  17. Enantioselective Ruthenium Catalyzed Carbonyl Allylation via Alkyne-Alcohol C-C Bond Forming Transfer Hydrogenation: Allene Hydrometallation vs. Oxidative Coupling

    PubMed Central

    Liang, Tao; Nguyen, Khoa D.; Zhang, Wandi; Krische, Michael J.

    2015-01-01

    Chiral ruthenium(II) complexes modified by Josiphos ligands catalyze the reaction of alkynes with primary alcohols to form homoallylic alcohols with excellent control of regio-, diastereo- and enantioselectivity. These processes represent the first examples of enantioselective carbonyl allylation using alkynes as allylmetal equivalents. PMID:25734220

  18. Synthesis of pyrroloindolines and furoindolines via cascade dearomatization of indole derivatives with carbenium ion.

    PubMed

    Liu, Chuan; Yin, Qin; Dai, Li-Xin; You, Shu-Li

    2015-04-01

    A highly efficient intermolecular cascade dearomatization of substituted indoles with benzodithiolylium tetrafluoroborate has been developed. This reaction provides a novel strategy to synthesise C3 methyl-substituted pyrroloindolines and furoindolines under mild reaction conditions, the utility of which has been demonstrated by the synthesis of esermethol and physovenine in a highly concise manner. PMID:25735950

  19. Enantioselective Sulfoxidation Catalyzed by a Bisguanidinium Diphosphatobisperoxotungstate Ion Pair.

    PubMed

    Ye, Xinyi; Moeljadi, Adhitya Mangala Putra; Chin, Kek Foo; Hirao, Hajime; Zong, Lili; Tan, Choon-Hong

    2016-06-13

    The first enantioselective tungstate-catalyzed oxidation reaction is presented. High enantioselectivities were achieved for a variety of drug-like phenyl and heterocyclic sulfides under mild conditions with H2 O2 , a cheap and environmentally friendly oxidant. Synthetic utility was demonstrated through the preparation of (S)-Lansoprazole, a commercial proton-pump inhibitor. The active ion-pair catalyst was identified to be bisguanidinium diphosphatobisperoxotungstate using Raman spectroscopy and computational studies. PMID:27150978

  20. Enantioselective Total Synthesis of (-)-Terengganensine A.

    PubMed

    Piemontesi, Cyril; Wang, Qian; Zhu, Jieping

    2016-05-23

    A seven-step enantioselective total synthesis of (-)-terengganensine A, a complex heptacyclic monoterpene indole alkaloid, was accomplished. Key steps included: a) Noyori's catalytic enantioselective transfer hydrogenation of the iminium salt to set up the absolute configuration at the C21 position; b) a highly diastereoselective C7 benzoyloxylation with dibenzoyl peroxide under mild conditions; and c) an integrated one-pot oxidative cleavage of cyclopentene/triple cyclization/hydrolysis sequence for the construction of the dioxa azaadamantane motif with complete control of four newly generated stereocenters. PMID:27094030

  1. Dearomatization Reactions of N-Heterocycles Mediated by Group 3 Complexes

    SciTech Connect

    Miller, Kevin L; Williams, Bryan N; Benitez, Diego; Carver, Colin T; Ogilby, Kevin R; Tkatchouk, Ekaterina; Goddard, William A; Diaconescu, Paula L

    2010-01-13

    Group 3 (Sc, Y, Lu, La) benzyl complexes supported by a ferrocene diamide ligand are reactive toward aromatic N-heterocycles by mediating their coupling and, in a few cases, the cleavage of their C-N bonds. When these complexes reacted with 2,2'-bipyridine or isoquinoline, they facilitated the alkyl migration of the benzyl ligand onto the pyridine ring, a process accompanied by the dearomatization of the N-heterocycle. The products of the alkyl-transfer reactions act as hydrogen donors in the presence of aromatic N-heterocycles, ketones, and azobenzene. Experimental and computational studies suggest that the hydrogen transfer takes place through a concerted mechanism. An interesting disproportionation reaction of the dearomatized, alkyl-substituted isoquinoline complexes is also reported.

  2. Metal-ligand cooperation by aromatization-dearomatization: a new paradigm in bond activation and "green" catalysis.

    PubMed

    Gunanathan, Chidambaram; Milstein, David

    2011-08-16

    In view of global concerns regarding the environment and sustainable energy resources, there is a strong need for the discovery of new, green catalytic reactions. For this purpose, fresh approaches to catalytic design are desirable. In recent years, complexes based on "cooperating" ligands have exhibited remarkable catalytic activity. These ligands cooperate with the metal center by undergoing reversible structural changes in the processes of substrate activation and product formation. We have discovered a new mode of metal-ligand cooperation, involving aromatization-dearomatization of ligands. Pincer-type ligands based on pyridine or acridine exhibit such cooperation, leading to unusual bond activation processes and to novel, environmentally benign catalysis. Bond activation takes place with no formal change in the metal oxidation state, and so far the activation of H-H, C-H (sp(2) and sp(3)), O-H, and N-H bonds has been demonstrated. Using this approach, we have demonstrated a unique water splitting process, which involves consecutive thermal liberation of H(2) and light-induced liberation of O(2), using no sacrificial reagents, promoted by a pyridine-based pincer ruthenium complex. An acridine pincer complex displays unique "long-range" metal-ligand cooperation in the activation of H(2) and in reaction with ammonia. In this Account, we begin by providing an overview of the metal-ligand cooperation based on aromatization-dearomatization processes. We then describe a range of novel catalytic reactions that we developed guided by these new modes of metal-ligand cooperation. These reactions include the following: (1) acceptorless dehydrogenation of secondary alcohols to ketones, (2) acceptorless dehydrogenative coupling of alcohols to esters, (3) acylation of secondary alcohols by esters with dihydrogen liberation, (4) direct coupling of alcohols and amines to form amides and polyamides with liberation of dihydrogen, (5) coupling of esters and amines to form amides

  3. Enantioselective Michael Addition of Water

    PubMed Central

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry. PMID:25529526

  4. Lithium Bromide/Water as Additives in Dearomatizing Samarium-Ketyl (Hetero)Arene Cyclizations.

    PubMed

    Rao, Chintada Nageswara; Bentz, Christoph; Reissig, Hans-Ulrich

    2015-11-01

    New conditions for dearomatizing samarium-ketyl (hetero)arene cyclizations are reported. In many examples of these samarium diiodide-mediated reactions, lithium bromide and water can be used as additives instead of the carcinogenic and mutagenic hexamethylphosphoramide (HMPA). The best results were obtained for the cyclizations of N-acylated indole derivatives delivering the expected indolines in good yields and excellent diastereoselectivities. A new type of cyclization delivering indolyl-substituted allene derivatives is also described. The scope and limitations of the lithium bromide/water system are discussed. PMID:26368916

  5. Enantioselective polyene cyclizations.

    PubMed

    Ungarean, Chad N; Southgate, Emma H; Sarlah, David

    2016-06-28

    The cyclization of polyolefins represents a powerful tool for the rapid generation of molecular complexity. Within the last decade, significant discoveries have been made in the development of methods for converting prochiral polyene substrates into the corresponding polycyclic products with high levels of enantiocontrol. This review highlights advances in the area of enantioselective polyene cyclizations and their use in the synthesis of complex secondary metabolites. PMID:27143099

  6. Silver(I)- or copper(II)-mediated dearomatization of aromatic ynones: direct access to spirocyclic scaffolds.

    PubMed

    James, Michael J; Cuthbertson, James D; O'Brien, Peter; Taylor, Richard J K; Unsworth, William P

    2015-06-22

    A high-yielding silver(I)- or copper(II)-catalyzed dearomatizing spirocyclization strategy allows the conversion of simple aromatic compounds that contain ynone substituents, including indole, anisole, pyrrole, and benzofuran derivatives, into functionalized spirocyclic scaffolds. A high-yielding asymmetric variant furnishes spirocyclic indolenines in up to 89:11 e.r. PMID:25960013

  7. Addition of 4-(cyclohex-1-en-1-yl)morpholine on 3-nitroindole: an unprecedented dearomatizing process.

    PubMed

    Andreini, Manuel; Chapellas, Fabien; Diab, Sonia; Pasturaud, Karine; Piettre, Serge R; Legros, Julien; Chataigner, Isabelle

    2016-03-01

    Nucleophilic enamines add spontaneously on heteroarenes 3-nitroindole and benzofuran to form a new C-C bond. With nitroindole and enamine , an unprecedented dearomatizing formal ene reaction occurs in a totally regio- and diastereo-selective manner. With 3-nitrobenzofuran and enamine , the reaction course is different and leads to the generation of a dienylphenol. PMID:26781166

  8. Enantioselective Synthesis of (-)-Dysiherbaine.

    PubMed

    Do, Ha; Kang, Chang Won; Cho, Joon Hyung; Gilbertson, Scott R

    2015-08-21

    Dysiherbaine, a natural product isolated from the Marine sponge Dysidea herbacea, has been shown to be a selective agonist of non-NMDA type glutamate receptors, kainate receptors. An enantioselective synthesis of dysiherbaine is reported. Metathesis of the diene followed by conversion of the resulting alkene to the amino alcohol and addition of the amino acid provides the natural product. This synthesis differs from previous approaches to the molecule in that the functionality on the tetrahydropyran ring is installed late in the route. PMID:26258884

  9. Catalytic Enantioselective Carboannulation with Allylsilanes

    PubMed Central

    Ball-Jones, Nicolas R.; Badillo, Joseph J.; Tran, Ngon T.; Franz, Annaliese K.

    2015-01-01

    The first catalytic asymmetric carboannulation with allylsilanes is presented. The enantioselective [3+2] annulation is catalyzed using a Sc(III)-indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]-borate (BArF) to enhance catalytic activity and control stereoselectivity. Functionalized cyclopentanes containing a quaternary carbon are derived from alkylidene oxindole, coumarin, and malonate substrates with high stereoselectivity. The enantioselective 1,4-conjugate addition and enantioselective lactone formation (via trapping of the β-silyl carbocation) is also described. PMID:25045133

  10. Catalytic enantioselective carboannulation with allylsilanes.

    PubMed

    Ball-Jones, Nicolas R; Badillo, Joseph J; Tran, Ngon T; Franz, Annaliese K

    2014-09-01

    The first catalytic asymmetric carboannulation with allylsilanes is presented. The enantioselective [3+2] annulation is catalyzed using a scandium(III)/indapybox complex with tetrakis-[3,5-bis(trifluoromethyl)phenyl]-borate (BArF) to enhance catalytic activity and control stereoselectivity. Functionalized cyclopentanes containing a quaternary carbon center are derived from alkylidene oxindole, coumarin, and malonate substrates with high stereoselectivity. The enantioselective 1,4-conjugate addition and enantioselective lactone formation (by trapping of the β-silyl carbocation) is also described. PMID:25045133

  11. Enantioselective effects in coordination compounds

    NASA Astrophysics Data System (ADS)

    Kurganov, Alexander A.; Ponomareva, T. M.; Davankov, Vadim A.

    1990-02-01

    The information that has appeared during the last 15 years relating to enantioselectivity in the formation and reactions of kinetically inert and kinetically labile complexes is classified in the present review. Attention is mainly given to chiral discrimination of ligands that are exchanged in the internal or external coordination spheres of the complexes. The occurrence of enantioselective effects has also been recorded in reactions of coordination compounds that occur without ligand exchange, in particular, in photochemical processes. The variety of forms in which enantioselectivity is displayed is shown and methods for studying it are described. The bibliography includes 223 references.

  12. Enantioselective Vinylogous Organocascade Reactions.

    PubMed

    Hepburn, Hamish B; Dell'Amico, Luca; Melchiorre, Paolo

    2016-08-01

    Cascade reactions are powerful tools for rapidly assembling complex molecular architectures from readily available starting materials in a single synthetic operation. Their marriage with asymmetric organocatalysis has led to the development of novel techniques, which are now recognized as reliable strategies for the one-pot enantioselective synthesis of stereochemically dense molecules. In recent years, even more complex synthetic challenges have been addressed by applying the principle of vinylogy to the realm of organocascade catalysis. The key to the success of vinylogous organocascade reactions is the unique ability of the chiral organocatalyst to transfer reactivity to a distal position without losing control on the stereo-determining events. This approach has greatly expanded the synthetic horizons of the field by providing the possibility of forging multiple stereocenters in remote positions from the catalyst's point of action with high selectivity, while simultaneously constructing multiple new bonds. This article critically describes the developments achieved in the field of enantioselective vinylogous organocascade reactions, charting the ideas, the conceptual advances, and the milestone reactions that have been essential for reaching highly practical levels of synthetic efficiency. PMID:27256039

  13. Photoassisted Synthesis of Complex Molecular Architectures: Dearomatization of Benzenoid Arenes with Aza-o-xylylenes via an Unprecedented [2+4] Reaction Topology.

    PubMed

    Kuznetsov, Dmitry M; Mukhina, Olga A; Kutateladze, Andrei G

    2016-06-01

    A new method was developed for the photoinduced dearomatization of arenes through an intramolecular cycloaddition with aza-o-xylylenes generated by excited-state intramolecular proton transfer (ESIPT) in the readily available photoprecursors. The [2+4] topology of this cycloaddition is unprecedented for photo-dearomatizations of benzenoid aromatic carbocycles. It provides rapid access to novel heterocycles, cyclohexadieno-oxazolidino-quinolinols, as valuable synthons for a broad range of post-photochemical transformations. PMID:27097759

  14. Catalytic, Enantioselective Addition of Alkyl Radicals to Alkenes via Visible-Light-Activated Photoredox Catalysis with a Chiral Rhodium Complex.

    PubMed

    Huo, Haohua; Harms, Klaus; Meggers, Eric

    2016-06-01

    An efficient enantioselective addition of alkyl radicals, oxidatively generated from organotrifluoroborates, to acceptor-substituted alkenes is catalyzed by a bis-cyclometalated rhodium catalyst (4 mol %) under photoredox conditions. The practical method provides yields up to 97% with excellent enantioselectivities up to 99% ee and can be classified as a redox neutral, electron-transfer-catalyzed reaction. PMID:27218134

  15. Atom-efficient regioselective 1,2-dearomatization of functionalized pyridines by an earth-abundant organolanthanide catalyst

    NASA Astrophysics Data System (ADS)

    Dudnik, Alexander S.; Weidner, Victoria L.; Motta, Alessandro; Delferro, Massimiliano; Marks, Tobin J.

    2014-12-01

    Developing earth-abundant, non-platinum metal catalysts for high-value chemical transformations is a critical challenge to contemporary chemical synthesis. Dearomatization of pyridine derivatives is an important transformation to access a wide range of valuable nitrogenous natural products, pharmaceuticals and materials. Here, we report an efficient 1,2-regioselective organolanthanide-catalysed pyridine dearomatization process using pinacolborane, which is compatible with a broad range of pyridines and functional groups and employs equimolar reagent stoichiometry. Regarding the mechanism, derivation of the rate law from NMR spectroscopic and kinetic measurements suggests first order in catalyst concentration, fractional order in pyridine concentration and inverse first order in pinacolborane concentration, with C=N insertion into the La-H bond as turnover-determining. An energetic span analysis affords a more detailed understanding of experimental activity trends and the unusual kinetic behaviour, and proposes the catalyst ‘resting’ state and potential deactivation pathways.

  16. Phosphathiahelicenes: synthesis and uses in enantioselective gold catalysis.

    PubMed

    Aillard, Paul; Voituriez, Arnaud; Dova, Davide; Cauteruccio, Silvia; Licandro, Emanuela; Marinetti, Angela

    2014-09-22

    Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine-Au(I) complex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96 % ee). PMID:25113927

  17. Hydrogenation and dehydrogenation iron pincer catalysts capable of metal-ligand cooperation by aromatization/dearomatization.

    PubMed

    Zell, Thomas; Milstein, David

    2015-07-21

    The substitution of expensive and potentially toxic noble-metal catalysts by cheap, abundant, environmentally benign, and less toxic metals is highly desirable and in line with green chemistry guidelines. We have recently discovered a new type of metal-ligand cooperation, which is based on the reversible dearomatization/aromatization of different heteroaromatic ligand cores caused by deprotonation/protonation of the ligand. More specifically, we have studied complexes of various transition metals (Ru, Fe, Co, Rh, Ir, Ni, Pd, Pt, and Re) bearing pyridine- and bipyridine-based PNP and PNN pincer ligands, which have slightly acidic methylene protons. In addition, we have discovered long-range metal-ligand cooperation in acridine-based pincer ligands, where the cooperation takes place at the electrophilic C-9 position of the acridine moiety leading to dearomatization of its middle ring. This type of metal-ligand cooperation was used for the activation of chemical bonds, including H-H, C-H (sp(2) and sp(3)), O-H, N-H, and B-H bonds. This unusual reactivity likely takes place in various catalytic hydrogenation, dehydrogenation, and related reactions. In this Account, we summarize our studies on novel bifunctional iron PNP and PNN pincer complexes, which were designed on the basis of their ruthenium congeners. Iron PNP pincer complexes serve as efficient (pre)catalysts for hydrogenation and dehydrogenation reactions under remarkably mild conditions. Their catalytic applications include atom-efficient and industrially important hydrogenation reactions of ketones, aldehydes, and esters to the corresponding alcohols. Moreover, they catalyze the hydrogenation of carbon dioxide to sodium formate in the presence of sodium hydroxide, the selective decomposition of formic acid to carbon dioxide and hydrogen, and the E-selective semihydrogenation of alkynes to give E-alkenes. These catalysts feature, compared to other iron-based catalysts, very high catalytic activities which in

  18. Cyclopalladated complexes in enantioselective catalysis

    NASA Astrophysics Data System (ADS)

    Dunina, Valeria V.; Gorunova, Olga N.; Zykov, P. A.; Kochetkov, Konstantin A.

    2011-01-01

    The results of the use of optically active palladacycles in enantioselective catalysis of [3,3]-sigmatropic rearrangements, aldol condensation, the Michael reaction and cross-coupling are analyzed. Reactions with allylic substrates or reagents and some other transformations are considered.

  19. Enantioselective Synthesis of (+)-Peganumine A.

    PubMed

    Piemontesi, Cyril; Wang, Qian; Zhu, Jieping

    2016-09-01

    A gram-scale enantioselective total synthesis of (+)-peganumine A was accomplished in 7 steps from commercially available 6-methoxytryptamine. Key steps included (a) a Liebeskind-Srogl cross-coupling; (b) a one-pot construction of the tetracyclic skeleton from an ω-isocyano-γ-oxo-aldehyde via a sequence of an unprecedented C-C bond forming lactamization and a transannular condensation; (c) a one-pot organocatalytic process merging two achiral building blocks into an octacyclic structure via a sequence of enantioselective Pictet-Spengler reaction followed by a transannular cyclization. This last reaction created two spirocycles and a 2,7-diazabicyclo[2.2.1]heptan-3-one unit with excellent control of both the absolute and relative stereochemistry of the two newly created quaternary stereocenters. PMID:27558528

  20. Enantioselective Total Synthesis of (-)-Pironetin

    PubMed Central

    Crimmins, Michael T.; Dechert, Anne-Marie R.

    2009-01-01

    The enantioselective total synthesis of pironetin has been achieved in 11 steps from known aldehyde 2. The synthesis relies on the formation of 5 out of 6 stereocenters through titanium mediated iterative aldol reactions. Key steps in this synthesis include an acetal aldol reaction to establish the stereochemistry at C8 and C9, an acetate aldol reaction, and “Evans” syn aldol reaction. PMID:19281219

  1. Catalytic Enantioselective Synthesis of Halocyclopropanes.

    PubMed

    Pons, Amandine; Ivashkin, Pavel; Poisson, Thomas; Charette, André B; Pannecoucke, Xavier; Jubault, Philippe

    2016-04-25

    A catalytic asymmetric synthesis of halocyclopropanes is described. The developed method is based on a carbenoid cyclopropanation of 2-haloalkenes with tert-butyl α-cyano-α-diazoacetate using a chiral rhodium catalyst that permits access to a broad range of highly functionalized chiral halocyclopropanes (F, Cl, Br, and I) in good yields, moderate diastereoselectivity, and excellent enantiomeric ratios. The reported methodology represents the first general catalytic enantioselective approach to halocyclopropanes. PMID:26945553

  2. Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

    PubMed Central

    2013-01-01

    Summary Enantioselective desymmetrization of meso-aziridines and meso-epoxides with various nucleophiles by organocatalysis has emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. PMID:24062828

  3. Enantioselective environmental behavior and cytotoxicity of chiral acaricide cyflumetofen.

    PubMed

    Sun, Dali; Pang, Junxiao; Zhou, Zhiqin; Jiao, Bining

    2016-10-01

    Enantioselective dissipation behavior of the new acaricide cyflumetofen (CYF) in citrus and soil, and its cytotoxicity to human liver hepatocellular carcinoma (HepG2) cells was investigated for the first time. The results of degradation experiment showed that roughly similar half-lives of (-)-CYF and (+)-CYF were achieved in citrus (16.5 and 19.8 d) and soil (6.37 and 6.99 d), respectively. EF values varied from 0.50 to 0.42 in citrus and from 0.49 to 0.48 in soil, indicating that slightly enantioselective degradation happened during experiment period. Moreover, indexes of MTT, LDH, ROS, MDA, SOD, and CAT were used to evaluate enantioselective cytotoxicity and oxidative stress of CYF enantiomers to HepG2 cells. Dose- and structure form-dependent phenomenon was observed with toxicity orders of (-)-CYF > rac-CYF > (+)-CYF. Despite the similar environmental degradation behavior, the toxicities of CYF enantiomers showed great difference, suggesting that (+)-CYF might be developed as potential substitute of rac-CYF for safety consideration. PMID:27424059

  4. Scalable enantioselective total synthesis of taxanes

    NASA Astrophysics Data System (ADS)

    Mendoza, Abraham; Ishihara, Yoshihiro; Baran, Phil S.

    2012-01-01

    Taxanes form a large family of terpenes comprising over 350 members, the most famous of which is Taxol (paclitaxel), a billion-dollar anticancer drug. Here, we describe the first practical and scalable synthetic entry to these natural products via a concise preparation of (+)-taxa-4(5),11(12)-dien-2-one, which has a suitable functional handle with which to access more oxidized members of its family. This route enables a gram-scale preparation of the ‘parent’ taxane—taxadiene—which is the largest quantity of this naturally occurring terpene ever isolated or prepared in pure form. The characteristic 6-8-6 tricyclic system of the taxane family, containing a bridgehead alkene, is forged via a vicinal difunctionalization/Diels-Alder strategy. Asymmetry is introduced by means of an enantioselective conjugate addition that forms an all-carbon quaternary centre, from which all other stereocentres are fixed through substrate control. This study lays a critical foundation for a planned access to minimally oxidized taxane analogues and a scalable laboratory preparation of Taxol itself.

  5. Enantioselective Total Synthesis of (+)-Reserpine

    PubMed Central

    Rajapaksa, Naomi S.; McGowan, Meredeth A.; Rienzo, Matthew

    2013-01-01

    A catalytic, enantioselective synthesis of (+)-reserpine is reported. The route features a highly diastereoselective, chiral catalyst-controlled formal aza-Diels–Alder reaction between a 6-methoxytryptamine-derived dihydro-β-carboline and an enantioenriched α-substituted enone to form a key tetracyclic intermediate. This approach addresses the challenge of setting the C3 stereogenic center by using catalyst control. Elaboration of the tetracycle to (+)-reserpine includes an intramolecular aldol cyclization and a highly diastereoselective hydrogenation of a sterically hindered enoate. PMID:23331099

  6. Enantioselective Functionalization of Allylic C-H Bonds Following a Strategy of Functionalization and Diversification

    PubMed Central

    Sharma, Ankit; Hartwig, John F.

    2013-01-01

    We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S or C-C bond at the allylic position in good yield with high branched-to-linear selectivity and excellent enantioselectivity (ee ≤ 97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated. PMID:24156776

  7. Enantioselective Cytotoxicity Profile of o,p’-DDT in PC 12 Cells

    PubMed Central

    Zhang, Chunlong; Wen, Yuezhong; Liu, Weiping

    2012-01-01

    Background The continued uses of dichlordiphenyltrichloroethane (DDT) for indoor vector control in some developing countries have recently fueled intensive debates toward the global ban of this persistent legacy contaminant. Current approaches for ecological and health risk assessment has ignored the chiral nature of DDT. In this study by employing an array of cytotoxicity related endpoints, we investigated the enantioselective cytotoxicity of o,p’-DDT. Principal Findings we demonstrated for the first time that R-(−)-o,p’-DDT caused more neuron cell death by inducing more severe oxidative stress, which selectively imbalanced the transcription of stress-related genes (SOD1, SOD2, HSP70) and enzyme (superoxide dismutase and lactate dehydrogenase) activities, and greater cellular apoptosis compared to its enantiomer S-(+)-o,p’-DDT at the level comparable to malaria area exposure (parts per million). We further elucidated enantioselective modes of action using microarray combined with enzyme-linked immunosorbent assay. The enantioselective apoptosis might involve three signaling pathways via caspase 3, tumor protein 53 (p53) and NFkB. Conclusions Based on DDT stereochemistry and results reported for other chiral pesticides, our results pointed to the same directional enantioselectivity of chiral DDT toward mammalian cells. We proposed that risk assessment on DDT should consider the enantiomer ratio and enantioselectivities. PMID:22937105

  8. Biomimetic Modeling of Copper Complexes: A Study of Enantioselective Catalytic Oxidation on D-(+)-Catechin and L-( − )-Epicatechin with Copper Complexes

    PubMed Central

    Mutti, Francesco G.; Pievo, Roberta; Sgobba, Maila; Gullotti, Michele; Santagostini, Laura

    2008-01-01

    The biomimetic catalytic oxidations of the dinuclear and trinuclear copper(II) complexes versus two catechols, namely, D-(+)-catechin and L-( − )-epicatechin to give the corresponding quinones are reported. The unstable quinones were trapped by the nucleophilic reagent, 3-methyl-2-benzothiazolinone hydrazone (MBTH), and have been calculated the molar absorptivities of the different quinones. The catalytic efficiency is moderate, as inferred by kinetic constants, but the complexes exhibit significant enantio-differentiating ability towards the catechols, albeit for the dinuclear complexes, this enantio-differentiating ability is lower. In all cases, the preferred enantiomeric substrate is D-(+)-catechin to respect the other catechol, because of the spatial disposition of this substrate. PMID:18825268

  9. Structurally Defined Molecular Hypervalent Iodine Catalysts for Intermolecular Enantioselective Reactions

    PubMed Central

    Haubenreisser, Stefan; Wöste, Thorsten H.; Martínez, Claudio; Ishihara, Kazuaki

    2015-01-01

    Abstract Molecular structures of the most prominent chiral non‐racemic hypervalent iodine(III) reagents to date have been elucidated for the first time. The formation of a chirally induced supramolecular scaffold based on a selective hydrogen‐bonding arrangement provides an explanation for the consistently high asymmetric induction with these reagents. As an exploratory example, their scope as chiral catalysts was extended to the enantioselective dioxygenation of alkenes. A series of terminal styrenes are converted into the corresponding vicinal diacetoxylation products under mild conditions and provide the proof of principle for a truly intermolecular asymmetric alkene oxidation under iodine(I/III) catalysis. PMID:26596513

  10. Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation

    NASA Astrophysics Data System (ADS)

    Lichtor, Phillip A.; Miller, Scott J.

    2012-12-01

    Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis has provided the only precedents. Although non-enzymatic catalysts that meet some of these challenges became known, a comprehensive solution has remained elusive. Here, we describe low molecular weight peptide-based catalysts, discovered through a combinatorial synthesis and screening protocol, that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features reminiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for the asymmetric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternative-site selectivity in comparison to oxidation catalysts previously described.

  11. Enantioselective synthesis of tetrafluorinated ribose and fructose.

    PubMed

    Linclau, Bruno; Boydell, A James; Timofte, Roxana S; Brown, Kylie J; Vinader, Victoria; Weymouth-Wilson, Alexander C

    2009-02-21

    A perfluoroalkylidene lithium mediated cyclisation approach for the enantioselective synthesis of a tetrafluorinated aldose (ribose) and of a tetrafluorinated ketose (fructose), both in the furanose and in the pyranose form, is described. PMID:19194597

  12. Enantioselective environmental toxicology of chiral pesticides.

    PubMed

    Ye, Jing; Zhao, Meirong; Niu, Lili; Liu, Weiping

    2015-03-16

    The enantioselective environmental toxic effect of chiral pesticides is becoming more important. As the industry develops, increasing numbers of chiral insecticides and herbicides will be introduced into use, potentially posing toxic effects on nontarget living beings. Chiral pesticides, including herbicides such as acylanilides, phenoxypropanoic acids, and imidazolinones, and insecticides such as synthetic pyrethroids, organophosphates, and DDT often behave enantioselectively during agricultural use. These compounds also pose unpredictable enantioselective ecological threats to nontarget living beings and/or humans, affecting the food chain and entire ecosystems. Thus, to investigate the enantioselective toxic effects of chiral insecticides and herbicides is necessary during environmental protection. The environmental toxicology of chiral pesticides, especially the findings obtained from studies conducted in our laboratory during the past 10 years, is reviewed. PMID:25643169

  13. Enantioselective Total Synthesis of (+)-Psiguadial B.

    PubMed

    Chapman, Lauren M; Beck, Jordan C; Wu, Linglin; Reisman, Sarah E

    2016-08-10

    The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features of the synthesis include (1) the enantioselective preparation of a key cyclobutane intermediate by a tandem Wolff rearrangement/asymmetric ketene addition, (2) a directed C(sp(3))-H alkenylation reaction to strategically forge the C1-C2 bond, and (3) a ring-closing metathesis to build the bridging bicyclo[4.3.1]decane terpene framework. PMID:27452034

  14. Catalytic, enantioselective, vinylogous aldol reactions.

    PubMed

    Denmark, Scott E; Heemstra, John R; Beutner, Gregory L

    2005-07-25

    In 1935, R. C. Fuson formulated the principle of vinylogy to explain how the influence of a functional group may be felt at a distant point in the molecule when this position is connected by conjugated double-bond linkages to the group. In polar reactions, this concept allows the extension of the electrophilic or nucleophilic character of a functional group through the pi system of a carbon-carbon double bond. This vinylogous extension has been applied to the aldol reaction by employing "extended" dienol ethers derived from gamma-enolizable alpha,beta-unsaturated carbonyl compounds. Since 1994, several methods for the catalytic, enantioselective, vinylogous aldol reaction have appeared, with which varying degrees of regio- (site), enantio-, and diastereoselectivity can be attained. In this Review, the current scope and limitations of this transformation, as well as its application in natural product synthesis, are discussed. PMID:15940727

  15. Enantioselective polymerization of epoxides using biaryl-linked bimetallic cobalt catalysts: a mechanistic study.

    PubMed

    Ahmed, Syud M; Poater, Albert; Childers, M Ian; Widger, Peter C B; LaPointe, Anne M; Lobkovsky, Emil B; Coates, Geoffrey W; Cavallo, Luigi

    2013-12-18

    The enantioselective polymerization of propylene oxide (PO) using biaryl-linked bimetallic salen Co catalysts was investigated experimentally and theoretically. Five key aspects of this catalytic system were examined: (1) the structural features of the catalyst, (2) the regio- and stereoselectivity of the chain-growth step, (3) the probable oxidation and electronic state of Co during the polymerization, (4) the role of the cocatalyst, and (5) the mechanism of monomer enchainment. Several important insights were revealed. First, density functional theory (DFT) calculations provided detailed structural information regarding the regio- and stereoselective chain-growth step. Specifically, the absolute stereochemistry of the binaphthol linker determines the enantiomer preference in the polymerization, and the interaction between the salen ligand and the growing polymer chain is a fundamental aspect of enantioselectivity. Second, a new bimetallic catalyst with a conformationally flexible biphenol linker was synthesized and found to enantioselectively polymerize PO, though with lower enantioselectivity than the binaphthol linked catalysts. Third, DFT calculations revealed that the active form of the catalyst has two active exo anionic ligands (chloride or carboxylate) and an endo polymer alkoxide which can ring-open an adjacent cobalt-coordinated epoxide. Fourth, calculations showed that initiation is favored by an endo chloride ligand, while propagation is favored by the presence of two exo carboxylate ligands. PMID:24199614

  16. Enantioselective Olefin Metathesis with Cyclometalated Ruthenium Complexes

    PubMed Central

    2015-01-01

    The success of enantioselective olefin metathesis relies on the design of enantioenriched alkylidene complexes capable of transferring stereochemical information from the catalyst structure to the reactants. Cyclometalation of the NHC ligand has proven to be a successful strategy to incorporate stereogenic atoms into the catalyst structure. Enantioenriched complexes incorporating this design element catalyze highly Z- and enantioselective asymmetric ring opening/cross metathesis (AROCM) of norbornenes and cyclobutenes, and the difference in ring strain between these two substrates leads to different propagating species in the catalytic cycle. Asymmetric ring closing metathesis (ARCM) of a challenging class of prochiral trienes has also been achieved. The extent of reversibility and effect of reaction setup was also explored. Finally, promising levels of enantioselectivity in an unprecedented Z-selective asymmetric cross metathesis (ACM) of a prochiral 1,4-diene was demonstrated. PMID:25137310

  17. Scalable, enantioselective taxane total synthesis

    PubMed Central

    Mendoza, Abraham; Ishihara, Yoshihiro; Baran, Phil S.

    2011-01-01

    Taxanes are a large family of terpenes comprising over 350 members, the most famous of which is Taxol (paclitaxel) — a billion-dollar anticancer drug. Here, we describe the first practical and scalable synthetic entry to these natural products via a concise preparation of (+)-taxa-4(5),11(12)-dien-2-one, which possesses a suitable functional handle to access more oxidised members of its family. This route enabled a gram-scale preparation of the ”parent” taxane, taxadiene, representing the largest quantity of this naturally occurring terpene ever isolated or prepared in pure form. The taxane family’s characteristic 6-8-6 tricyclic system containing a bridgehead alkene is forged via a vicinal difunctionalisation/Diels–Alder strategy. Asymmetry is introduced by means of an enantioselective conjugate addition that forms an all-carbon quaternary centre, from which all other stereocentres are fixed via substrate control. This study lays a critical foundation for a planned access to minimally oxidised taxane analogs and a scalable laboratory preparation of Taxol itself. PMID:22169867

  18. Enantioselective Total Synthesis of Tricyclic Myrmicarin Alkaloids

    PubMed Central

    Movassaghi, Mohammad; Ondrus, Alison E.

    2010-01-01

    An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium–catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper–catalyzed enantioselective conjugate reduction of a β-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented. PMID:16178549

  19. Enantioselective Total Synthesis of Secalonic Acid E.

    PubMed

    Ganapathy, Dhandapani; Reiner, Johannes R; Löffler, Lorenz E; Ma, Ling; Gnanaprakasam, Boopathy; Niepötter, Benedikt; Koehne, Ingo; Tietze, Lutz F

    2015-11-16

    The first enantioselective synthesis of a secalonic acid containing a dimeric tetrahydroxanthenone skeleton is described, using a Wacker-type cyclization of a methoxyphenolic compound to form a chiral chroman with a quaternary carbon stereogenic center with >99% ee. Further steps are a Sharpless dihydroxylation and a Dieckmann condensation to give a tetrahydroxanthenone. A late-stage one-pot palladium-catalyzed Suzuki-dimerization reaction leads to the 2,2'-biphenol linkage to complete the enantioselective total synthesis of secalonic acid E in 18 steps with 8% overall yield. PMID:26447631

  20. The Catalytic Enantioselective Total Synthesis of (+)-Liphagal**

    PubMed Central

    Day, Joshua J.; McFadden, Ryan M.; Virgil, Scott C.; Kolding, Helene; Alleva, Jennifer L.; Stoltz, Brian M.

    2012-01-01

    Ring a ding: The first catalytic enantioselective total synthesis of the meroterpenoid natural product (+)-liphagal is disclosed. The approach showcases a variety of technology including enantioselective enolate alkylation, a photochemical alkyne-alkene [2+2] reaction, microwave-assisted metal catalysis, and an intramolecular aryne capture cyclization reaction. Pivotal to the successful completion of the synthesis was a sequence involving ring expansion from a [6-5-4] tricycle to a [6-7] bicyclic core followed by stereoselective hydrogenation of a sterically occluded tri-substituted olefin to establish the trans homodecalin system found in the natural product. PMID:21671325

  1. A Synthesis of the Carbon Skeleton of Maoecrystal V

    PubMed Central

    Krawczuk, Paul J.; Schöne, Niklas; Baran, Phil S.

    2009-01-01

    An enantioselective synthesis of the maoecrystal V (1) carbon skeleton is described. The key transformations include arylation of a 1,3-dicarbonyl compound with a triarylbismuth(V)dichloride species, oxidative dearomatization of a phenol, and a subsequent intramolecular Diels-Alder reaction. PMID:19795876

  2. The Oxidation of Pyrrole.

    PubMed

    Howard, James K; Rihak, Kieran J; Bissember, Alex C; Smith, Jason A

    2016-01-01

    The dearomatization of heterocycles has been a powerful means for producing functional molecules in synthesis. In the case of pyrroles, reductive methods (such as the Birch reduction) have been most widely exploited, while oxidative methods are generally dismissed as too difficult or unpredictable to be useful. However, since the early twentieth century considerable research has been carried out on the controlled oxidation of pyrroles to give highly functionalized products, using a variety of oxidants. This review presents a summary of all work up until the present day in the area of pyrrole oxidation, looking at the use of peroxide, singlet oxygen, hypervalent iodine reagents, a range or organic and inorganic oxidants, and electrochemical approaches. It also offers some perspective on the potential future role of pyrrole oxidation in synthesis. PMID:26294175

  3. Enantioselective Synthesis of L-CCG-I.

    PubMed

    Chavan, Subhash P; Sharma, Pallavi; Sivappa, Rasapalli; Bhadbhade, Mohan M; Gonnade, Rajesh G; Kalkote, Uttam R

    2003-08-22

    Introduction of natural menthol as the chiral auxiliary in a gamma-Br-alpha,beta-unsaturated ester leads to enantioselective generation of three chiral centers in a single step on reaction with a glycine anion equivalent to provide L-CCG-I in 94% ee. PMID:12919057

  4. Enantioselective Transaminations by Dendrimeric Enzyme Mimics

    PubMed Central

    Wei, Sujun; Kenesky, Craig

    2007-01-01

    PAMAM dendrimers have been constructed with a pyridoxamine core, and chiral capping amino groups. Transamination to form phenylalanine and alanine from their related ketoacids produced enantioselectivities induced by the formally remote chiral caps, supporting computer models that indicate folding of the dendrimer chains back into the core region. PMID:18596840

  5. Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 2. Irritation and inflammation.

    PubMed

    Ernstgård, Lena; Iregren, Anders; Juran, Stephanie; Sjögren, Bengt; van Thriel, Christoph; Johanson, Gunnar

    2009-04-01

    Low aromatic and dearomatized white spirits (deWS) are often considered less hazardous to health than 'standard' or aromatic white sprit (stdWS, 15-20% aromatics). However, data on health effects of deWS in humans are sparse and controlled exposure studies are lacking. The aim of this study was to compare deWS and stdWS with respect to irritation and inflammation. Six female and six male healthy volunteers were exposed on five occasions in balanced order to 100 or 300 mg m(-3) deWS (0.002% aromatics) or stdWS (19% aromatics), or to clean air, for 4 h at rest. Discomfort in the eyes, nose and throat and breathing difficulty were assessed by ratings on visual analogue scales. The only significant increases in ratings (compared to clean air) were seen for eye irritation at the high stdWS exposure and for solvent smell at all but the low deWS exposure. Excluding smell, all average ratings were at the lower end of the 0-100 mm scale, and did not exceed the verbal expression 'somewhat'. Ratings during stdWS exposure tended to be higher than during deWS exposure. No exposure-related effects on pulmonary function, nasal swelling, nasal airway resistance, breathing frequency, blinking frequency, plasma inflammatory markers (C-reactive protein, interleukin-6) or biochemical variables (sodium, potassium, amylase, creatine kinase, urate) were seen. In conclusion, stdWS appears to be slightly more irritating than deWS. This could, however, not be confirmed by objective measurements. PMID:19086013

  6. Phosphine-mediated Highly Enantioselective Spirocyclization with Ketimines as Substrates.

    PubMed

    Han, Xiaoyu; Chan, Wai-Lun; Yao, Weijun; Wang, Yongjiang; Lu, Yixin

    2016-05-23

    Phosphine-catalyzed enantioselective annulation reactions involving ketimines are a daunting synthetic challenge owing to the intrinsic low reactivity of ketimine substrates. A highly enantioselective [3+2] cycloaddition reaction that makes use of isatin-derived ketimines as reaction partners was developed. Notably, both simple and γ-substituted allenoates could be utilized, and various 3,2'-pyrrolidinyl spirooxindoles with a tetrasubstituted stereocenter were obtained in excellent yields and with nearly perfect enantioselectivity (>98 % ee in all cases). PMID:27080309

  7. Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

    NASA Astrophysics Data System (ADS)

    Sato, Yukari; Natsume, Ryo; Prokop, Zbynek; Brezovsky, Jan; Chaloupkova, Radka; Damborsky, Jiri; Nagata, Yuji; Senda, Toshiya

    Enzymes are widely used for the synthesis of pharmaceuticals, agrochemicals, and food additives because they can catalyze high enantioselective transformations. In order to construct selective enzymes by protein engineering, it is important to understand the molecular basis of enzyme-substrate interactions that contribute to enantioselectivity. The haloalkane dehalogenase DbjA showed high enantioselectivity for two racemic mixtures: α-bromoesters and β-bromoalkanes. Thermodynamic analysis, protein crystallography, and computer simulations indicated that DbjA carries two bases for the enantiodiscrimination of each racemic mixture. This study helps us understand the molecular basis of the enantioselectivity and opens up new possibilities for constructing enantiospecific biocatalysts through protein engineering.

  8. Highly enantioselective reductive cyclization of acetylenic aldehydes via rhodium catalyzed asymmetric hydrogenation.

    PubMed

    Rhee, Jong Uk; Krische, Michael J

    2006-08-23

    Catalytic hydrogenation of acetylenic aldehydes 1a-12a using chirally modified cationic rhodium catalysts enables highly enantioselective reductive cyclization to afford cyclic allylic alcohols 1b-12b. Using an achiral hydrogenation catalyst, the chiral racemic acetylenic aldehydes 13a-15a engage in highly syn-diastereoselective reductive cyclizations to afford cyclic allylic alcohols 13b-15b. Ozonolysis of cyclization products 7b and 9b allows access to optically enriched alpha-hydroxy ketones 7c and 9c. Reductive cyclization of enyne 7a under a deuterium atmosphere provides the monodeuterated product deuterio-7b, consistent with a catalytic mechanism involving alkyne-carbonyl oxidative coupling followed by hydrogenolytic cleavage of the resulting oxametallacycle. These hydrogen-mediated transformations represent the first examples of the enantioselective reductive cyclization of acetylenic aldehydes. PMID:16910650

  9. Vancomycin Molecular Interactions: Antibiotic and Enantioselective Mechanisms

    NASA Astrophysics Data System (ADS)

    Ward, Timothy J.; Gilmore, Aprile; Ward, Karen; Vowell, Courtney

    Medical studies established that vancomycin and other related macrocyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide structurally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin's mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition.

  10. Enantioselective aldol reactions with masked fluoroacetates.

    PubMed

    Saadi, Jakub; Wennemers, Helma

    2016-03-01

    Despite the growing importance of organofluorines as pharmaceuticals and agrochemicals, the stereoselective introduction of fluorine into many prominent classes of natural products and chemotherapeutic agents is difficult. One long-standing unsolved challenge is the enantioselective aldol reaction of fluoroacetate to enable access to fluorinated analogues of medicinally relevant acetate-derived compounds, such as polyketides and statins. Herein we present fluoromalonic acid halfthioesters as biomimetic surrogates of fluoroacetate and demonstrate their use in highly stereoselective aldol reactions that proceed under mild organocatalytic conditions. We also show that the methodology can be extended to formal aldol reactions with fluoroacetaldehyde and consecutive aldol reactions. The synthetic utility of the fluorinated aldol products is illustrated by the synthesis of a fluorinated derivative of the top-selling drug atorvastatin. The results show the prospects of the method for the enantioselective introduction of fluoroacetate to access a wide variety of highly functionalized fluorinated compounds. PMID:26892561

  11. Enzymatic Enantioselective Decarboxylative Protonation of Heteroaryl Malonates

    PubMed Central

    Lewin, Ross; Goodall, Mark; Thompson, Mark L; Leigh, James; Breuer, Michael; Baldenius, Kai; Micklefield, Jason

    2015-01-01

    The enzyme aryl/alkenyl malonate decarboxylase (AMDase) catalyses the enantioselective decarboxylative protonation (EDP) of a range of disubstituted malonic acids to give homochiral carboxylic acids that are valuable synthetic intermediates. AMDase exhibits a number of advantages over the non-enzymatic EDP methods developed to date including higher enantioselectivity and more environmentally benign reaction conditions. In this report, AMDase and engineered variants have been used to produce a range of enantioenriched heteroaromatic α-hydroxycarboxylic acids, including pharmaceutical precursors, from readily accessible α-hydroxymalonates. The enzymatic method described here represents an improvement upon existing synthetic chemistry methods that have been used to produce similar compounds. The relationship between the structural features of these new substrates and the kinetics associated with their enzymatic decarboxylation is explored, which offers further insight into the mechanism of AMDase. PMID:25766433

  12. Enantioselective aldol reactions with masked fluoroacetates

    NASA Astrophysics Data System (ADS)

    Saadi, Jakub; Wennemers, Helma

    2016-03-01

    Despite the growing importance of organofluorines as pharmaceuticals and agrochemicals, the stereoselective introduction of fluorine into many prominent classes of natural products and chemotherapeutic agents is difficult. One long-standing unsolved challenge is the enantioselective aldol reaction of fluoroacetate to enable access to fluorinated analogues of medicinally relevant acetate-derived compounds, such as polyketides and statins. Herein we present fluoromalonic acid halfthioesters as biomimetic surrogates of fluoroacetate and demonstrate their use in highly stereoselective aldol reactions that proceed under mild organocatalytic conditions. We also show that the methodology can be extended to formal aldol reactions with fluoroacetaldehyde and consecutive aldol reactions. The synthetic utility of the fluorinated aldol products is illustrated by the synthesis of a fluorinated derivative of the top-selling drug atorvastatin. The results show the prospects of the method for the enantioselective introduction of fluoroacetate to access a wide variety of highly functionalized fluorinated compounds.

  13. Enantioselective Bromo-oxycyclization of Silanol.

    PubMed

    Xia, Zilei; Hu, Jiadong; Shen, Zhigao; Wan, Xiaolong; Yao, Qizheng; Lai, Yisheng; Gao, Jin-Ming; Xie, Weiqing

    2016-01-01

    Relying on the nucleophilicity of silanol for building up silicon-incorporated scaffold with an enantiopure tetrasubstituted carbon center remains elusive. In this report, asymmetric bromo-oxycyclization of olefinic silanol by using chiral anionic phase-transfer catalyst is described. This protocol provided a facile entry to a wide arrangement of enantiopure benzoxasilole in moderate to excellent enantioselectivities depending on the unique reactivity of bromine/N-benzyl-DABCO complex. PMID:26654658

  14. Palladium-Catalyzed, Enantioselective Heine Reaction

    PubMed Central

    2016-01-01

    Aziridines are important synthetic intermediates for the generation of nitrogen-containing molecules. N-Acylaziridines undergo rearrangement by ring expansion to produce oxazolines, a process known as the Heine reaction. The first catalytic, enantioselective Heine reaction is reported for meso-N-acylaziridines where a palladium(II)–diphosphine complex is employed. The highly enantioenriched oxazoline products are valuable organic synthons and potential ligands for transition-metal catalysis. PMID:27398262

  15. Short, Enantioselective Total Synthesis of Chatancin**

    PubMed Central

    Zhao, Yu-Ming

    2014-01-01

    An enantioselective total synthesis of the polycyclic diterpene chatancin (1), a potent PAF antagonist, is reported. Proceeding in seven steps from dihydrofarnesal, this synthetic route was designed to circumvent macrocyclization-based strategies to complex, cyclized cembranoids. The described synthesis requires only six chromatographic purifications, is high yielding, and avoids protecting group chemistry. An X-ray crystal structure of this fragile marine natural product was obtained. PMID:25470723

  16. Enantioselective Phytotoxicity of Imazamox Against Maize Seedlings.

    PubMed

    Wei, Jing; Zhang, Xiaoxiao; Li, Xuesheng; Zeng, Dongqiang; Tan, Huihua

    2016-02-01

    There is increasing concern about the enantioselective effects of chiral herbicides. To study the enantioselective toxicity of the chiral herbicide imazamox on maize, maize seedlings (Zhengda 619, Zea mays L.) were exposed to imazamox racemate and enantiomers in hydroponic experiments. The results showed that imazamox enantiomers selectively affected maize. The effective concentration of Rac-, S- and R-imazamox that caused 50 % inhibition after 5 days treatments (EC50,5d) were 0.4212, 1.2142 and 0.2460 mg L(-1), respectively, for maize root length; 0.0002, 0.1005, 0.0032 mg L(-1), respectively, for maize root fresh weight; 0.7114, 1.4056 and 0.4530 mg L(-1), respectively, for maize shoot height; 0.6220, 1.5418, 0.2286 mg L(-1), respectively, for maize shoot fresh weight; and 0.1100, 0.3306, 0.0307 mg L(-1), respectively, for the total chlorophyll content of leaves. The root morphological parameters and root activity reflected the toxicity effects in the order R-imazamox > Rac-imazamox > S-imazamox. Maize roots were more sensitive to imazamox than maize shoots. The chiral herbicide imazamox poses enantioselective phytotoxicity on maize seedlings: the order of toxicity is R-imazamox > Rac-imazamox > S-imazamox. PMID:26508428

  17. Enantioselective Transport and Biotransformation of Chiral Hydroxylated Metabolites of Polychlorinated Biphenyls in Whole Poplar Plants

    PubMed Central

    2015-01-01

    Hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) have been found to be ubiquitous in the environment due to the oxidative metabolism of their parent PCBs. With more polarity, OH-PCBs may be more toxic and mobile than their parent compounds. However, the behavior and fate of OH-PCBs have been neglected in the environment because they are not the original contaminants. Some of these hydroxylated metabolites are chiral, and chiral compounds can be used to probe biological metabolic processes. Therefore, chiral OH-PCBs were selected to study their uptake, translocation, transformation, and enantioselectivity in plants in this work. Poplars (Populus deltoides × nigra, DN34), a model plant with complete genomic sequence, were hydroponically exposed to 5-hydroxy-2,2′,3,4′,6-pentachlorobiphenyl (5-OH-PCB91) and 5-hydroxy-2,2′,3,5′,6-pentachlorobiphenyl (5-OH-PCB95) for 10 days. Chiral 5-OH-PCB91 and 5-OH-PCB95 were clearly shown to be sorbed, taken up, and translocated in whole poplars, and they were detected in various tissues of whole poplars. However, the enantioselectivity of poplar for 5-OH-PCB91 and 5-OH-PCB95 proved to be quite different. The second-eluting enantiomer of OH-PCB95, separated on a chiral column (Phenomenex Lux Cellulose-1), was enantioselectively removed in whole poplar. Enantiomeric fractions in the middle xylem, top bark, top xylem, and stem, reached 0.803 ± 0.022, 0.643 ± 0.110, 0.835 ± 0.087, and 0.830 ± 0.029, respectively. Therefore, 5-OH-PCB95 was significantly enantioselectively biotransformed inside poplar tissues, in contrast to nearly racemic mixtures of 5-OH-PCB95 remaining in hydroponic solutions. Unlike 5-OH-PCB95, 5-OH-PCB91 remained nearly racemic in most tissues of whole poplars during 10 day exposure, suggesting the enantiomers of 5-OH-PCB91 were equally transported and metabolized in whole poplars. This is the first evidence of enantioselectivity of chiral OH-PCBs and suggests that poplars can

  18. Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids.

    PubMed

    Song, Song; Zhu, Shou-Fei; Pu, Liu-Yang; Zhou, Qi-Lin

    2013-06-01

    Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF(-) =tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. PMID:23610004

  19. Organocatalytic enantioselective peroxidation of ketimines derived from isatins.

    PubMed

    Nakamura, Shuichi; Takahashi, Shun

    2015-06-01

    The first catalytic enantioselective addition of hydroperoxides to ketimines derived from isatins has been developed. Excellent yields and enantioselectivities were observed for the reaction of various ketimines with peroxides using a cinchona alkaloid sulfonamide catalyst. Both enantiomers of products could be obtained by using pseudoenantiomeric chiral catalysts. The obtained product can be converted to optically active α-amino hydroperoxide. PMID:25965522

  20. Organocatalytic Enantioselective Synthesis of Pyrazoles Bearing a Quaternary Stereocenter.

    PubMed

    Vila, Carlos; Amr, Fares Ibrahim; Blay, Gonzalo; Muñoz, M Carmen; Pedro, José R

    2016-05-20

    An efficient one-pot asymmetric synthesis of pyrazoles bearing a chiral quaternary stereocenter has been developed. Quinine-derived thiourea catalyzed the enantioselective addition of pyrazolones to isatin-derived ketimines, providing the corresponding acetylated pyrazoles after in situ treatment with Ac2 O/Et3 N. The corresponding pyrazoles were afforded in high yields and excellent enantioselectivities. PMID:27038062

  1. Bovine serum albumin-cobalt(ii) Schiff base complex hybrid: an efficient artificial metalloenzyme for enantioselective sulfoxidation using hydrogen peroxide.

    PubMed

    Tang, Jie; Huang, Fuping; Wei, Yi; Bian, Hedong; Zhang, Wei; Liang, Hong

    2016-05-10

    An artificial metalloenzyme (BSA-CoL) based on the incorporation of a cobalt(ii) Schiff base complex {CoL, H2L = 2,2'-[(1,2-ethanediyl)bis(nitrilopropylidyne)]bisphenol} with bovine serum albumin (BSA) has been synthesized and characterized. Attention is focused on the catalytic activity of this artificial metalloenzyme for enantioselective oxidation of a variety of sulfides with H2O2. The influences of parameters such as pH, temperature, and the concentration of catalyst and oxidant on thioanisole as a model are investigated. Under optimum conditions, BSA-CoL as a hybrid biocatalyst is efficient for the enantioselective oxidation of a series of sulfides, producing the corresponding sulfoxides with excellent conversion (up to 100%), chemoselectivity (up to 100%) and good enantiomeric purity (up to 87% ee) in certain cases. PMID:27075699

  2. Dephenolization, dearomatization and detoxification of olive mill wastewater with sonication combined with additives and radical scavengers.

    PubMed

    Sponza, Delia Teresa; Oztekin, Rukiye

    2014-05-01

    In this study, the effects of some additives [manganese (III) oxide (Mn3O4), Cu(+2), Fe(0) and potassium iodate (KIO3)] and some radical scavengers [sodium carbonate (Na2CO3), perfluorohexane (C6F14) and t-butyl alcohol (C4H10O)] on the sonication of olive mill effluent wastewater (OMW) were investigated since the wastewaters of this industry are removed with low efficiencies. The maximum total phenol and total aromatic amines (TAAs) removal efficiencies were 88% and 79%, respectively, at 60°C with only 150 min sonication. The maximum phenol removal was found as 98% with 19 mg L(-1) perfluorohexane and 5 mg L(-1) Fe(0) while the maximum TAAs removal was 99% with 16 mg L(-1) KIO3. Catechol, tyrosol, quercetin, caffeic acid, 4-methyl catechol, 2-phenylphenol (2-PHE) and 3-phenyl phenol (3-PHE) were detected as phenol intermediates while trimethlyaniline, aniline, o-toluidine, o-anisidine, dimethylaniline, ethylbenzene and durene were identified as TAAs in the OMW. The maximum acute toxicity removals were 96% and 99% in Vibrio fischeri and Daphnia magna, respectively. Total phenol, TAAs and the toxicity in an OMW were removed efficiently and cost-effectively through sonication. PMID:24315030

  3. Crystalline-gradient polycarbonates prepared from enantioselective terpolymerization of meso-epoxides with CO2

    NASA Astrophysics Data System (ADS)

    Liu, Ye; Ren, Wei-Min; He, Ke-Ke; Lu, Xiao-Bing

    2014-12-01

    The development of efficient processes for CO2 transformation into useful products is a long-standing goal for chemists, since CO2 is an abundant, inexpensive and non-toxic renewable C1 resource. Here we describe the enantioselective copolymerization of 3,4-epoxytetrahydrofuran with CO2 mediated by biphenol-linked dinuclear cobalt complex, affording the corresponding polycarbonate with >99% carbonate linkages and excellent enantioselectivity (up to 99% enantiomeric excess). Notably, the resultant isotactic polycarbonate is a typical semicrystalline polymer, possessing a melting point of 271 °C. Furthermore, the enantioselective terpolymerization of 3,4-epoxytetrahydrofuran, cyclopentene oxide and CO2 mediated by this dinuclear cobalt complex gives novel gradient polycarbonates, in which the decrement of one component and the increment of the other component occur sequentially from one chain end to the other end. The resultant terpolymers show perfectly isotactic structure and have unique crystalline-gradient nature, in which the crystallinity continuously varies along the main chain.

  4. Crystalline-gradient polycarbonates prepared from enantioselective terpolymerization of meso-epoxides with CO2.

    PubMed

    Liu, Ye; Ren, Wei-Min; He, Ke-Ke; Lu, Xiao-Bing

    2014-01-01

    The development of efficient processes for CO2 transformation into useful products is a long-standing goal for chemists, since CO2 is an abundant, inexpensive and non-toxic renewable C1 resource. Here we describe the enantioselective copolymerization of 3,4-epoxytetrahydrofuran with CO2 mediated by biphenol-linked dinuclear cobalt complex, affording the corresponding polycarbonate with >99% carbonate linkages and excellent enantioselectivity (up to 99% enantiomeric excess). Notably, the resultant isotactic polycarbonate is a typical semicrystalline polymer, possessing a melting point of 271 °C. Furthermore, the enantioselective terpolymerization of 3,4-epoxytetrahydrofuran, cyclopentene oxide and CO2 mediated by this dinuclear cobalt complex gives novel gradient polycarbonates, in which the decrement of one component and the increment of the other component occur sequentially from one chain end to the other end. The resultant terpolymers show perfectly isotactic structure and have unique crystalline-gradient nature, in which the crystallinity continuously varies along the main chain. PMID:25477252

  5. Stomatal behaviors reflect enantioselective phytotoxicity of chiral herbicide dichlorprop in Arabidopsis thaliana.

    PubMed

    Chen, Zunwei; Chen, Hui; Zou, Yuqin; Wen, Yuezhong

    2016-08-15

    Stomata in plants play vital roles in water transpiration and gas exchange necessary for photosynthesis, which are critical for the plants growth. Until now, however, the effect of chiral herbicides on the response of stomata was poorly understood. To unveil this puzzle, the enantioselective effect of chiral herbicide dichloroprop (DCPP) on stomata in Arabidopsis thaliana was investigated. It was found that (R)-DCPP preferentially promoted the extent of stomatal opening in Arabidopsis leaves, resulting in 59.84% enhancement at 0.3μmol·L(-1) comparing to the control, where (S)- and (Rac)-DCPP exhibited no significant differences. Enantioselectivity was also observed in the response of stomata to DCPP. To better understand the mechanism involved, the reactive oxygen species (ROS) production and antioxidant system defense were measured. Interestingly, the ROS production in Arabidopsis leaves was also enantioselective. The (R)-DCPP treatments resulted in 6.08-fold enhancement compared with the control, whereas 1.35- and 2.51-fold increases occurred in (S)-DCPP and (Rac)-DCPP treatments, respectively. The promoting of stomatal opening was positively correlated with ROS production. In addition, the antioxidant system response provided evidence of oxidative stress and damage caused by DCPP. This study confirmed that the ROS produced by DCPP promoted stomatal opening and suggested a potential sight to elucidate the phytotoxicity of chiral herbicides. PMID:27092421

  6. Catalytic Enantioselective Functionalization of Unactivated Terminal Alkenes.

    PubMed

    Coombs, John R; Morken, James P

    2016-02-18

    Terminal alkenes are readily available functional groups which appear in α-olefins produced by the chemical industry, and they appear in the products of many contemporary synthetic reactions. While the organic transformations that apply to alkenes are amongst the most studied reactions in all of chemical synthesis, the number of reactions that apply to nonactivated terminal alkenes in a catalytic enantioselective fashion is small in number. This Minireview highlights the cases where stereocontrol in catalytic reactions of 1-alkenes is high enough to be useful for asymmetric synthesis. PMID:26764019

  7. Conjugate addition-enantioselective protonation reactions.

    PubMed

    Phelan, James P; Ellman, Jonathan A

    2016-01-01

    The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals. PMID:27559372

  8. Conjugate addition–enantioselective protonation reactions

    PubMed Central

    Phelan, James P

    2016-01-01

    Summary The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals. PMID:27559372

  9. Catalytic Enantioselective Synthesis of Quaternary Carbon Stereocenters

    PubMed Central

    Quasdorf, Kyle W.; Overman, Larry E.

    2015-01-01

    Preface Quaternary carbon stereocenters–carbon atoms to which four distinct carbon substituents are attached–are common features of molecules found in nature. However, prior to recent advances in chemical catalysis, there were few methods available for constructing single stereoisomers of this important structural motif. Here we discuss the many catalytic enantioselective reactions developed during the past decade for synthesizing organic molecules containing such carbon atoms. This progress now makes it possible to selectively incorporate quaternary stereocenters in many high-value organic molecules for use in medicine, agriculture, and other areas. PMID:25503231

  10. Enantioselective cellular uptake of chiral semiconductor nanocrystals

    NASA Astrophysics Data System (ADS)

    Martynenko, I. V.; Kuznetsova, V. A.; Litvinov, I. K.; Orlova, A. O.; Maslov, V. G.; Fedorov, A. V.; Dubavik, A.; Purcell-Milton, F.; Gun'ko, Yu K.; Baranov, A. V.

    2016-02-01

    The influence of the chirality of semiconductor nanocrystals, CdSe/ZnS quantum dots (QDs) capped with L- and D-cysteine, on the efficiency of their uptake by living Ehrlich Ascite carcinoma cells is studied by spectral- and time-resolved fluorescence microspectroscopy. We report an evident enantioselective process where cellular uptake of the L-Cys QDs is almost twice as effective as that of the D-Cys QDs. This finding paves the way for the creation of novel approaches to control the biological properties and behavior of nanomaterials in living cells.

  11. Enantioselective Synthesis of Spiroindenes by Enol-Directed Rhodium(III)-Catalyzed C–H Functionalization and Spiroannulation

    PubMed Central

    Reddy Chidipudi, Suresh; Burns, David J; Khan, Imtiaz; Lam, Hon Wai

    2015-01-01

    Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp2)-H functionalization and oxidative annulation with alkynes to give spiroindenes containing all-carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O-bound rhodium enolate into the C-bound isomer, appear to be critical for high enantiomeric excesses. PMID:26404643

  12. Enantioselective Synthesis of Spiroindenes by Enol-Directed Rhodium(III)-Catalyzed C-H Functionalization and Spiroannulation.

    PubMed

    Reddy Chidipudi, Suresh; Burns, David J; Khan, Imtiaz; Lam, Hon Wai

    2015-11-16

    Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp(2))-H functionalization and oxidative annulation with alkynes to give spiroindenes containing all-carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O-bound rhodium enolate into the C-bound isomer, appear to be critical for high enantiomeric excesses. PMID:26404643

  13. Copper-Catalyzed Aerobic Enantioselective Cross-Dehydrogenative Coupling of N-Aryl Glycine Esters with Terminal Alkynes.

    PubMed

    Xie, Zhiyu; Liu, Xigong; Liu, Lei

    2016-06-17

    A copper-catalyzed enantioselective cross-coupling of a Csp3-H moiety (N-aryl glycine ester) with a Csp-H component (terminal alkyne) using molecular oxygen as the terminal oxidant is described for the first time. The sustainable method provides an efficient and environmentally friendly approach to rapidly prepare a diverse array of optically active non-natural α-amino acids. PMID:27269737

  14. Enantioselective Synthesis of Dideoxy-tetrafluorinated Hexoses.

    PubMed

    Golten, Samuel; Fontenelle, Clément Q; Timofte, Roxana S; Bailac, Laura; Light, Mark; Sebban, Muriel; Oulyadi, Hassan; Linclau, Bruno

    2016-06-01

    Carbohydrates typically have low affinities to protein binding sites, and the development of carbohydrate mimetics with improved binding is therefore of interest. Tetrafluorination of monosaccharides is one of the strategies currently under investigation for that purpose. The synthesis of the required tetrafluorinated monosaccharides is achieved by a fluorinated building block approach. The enantioselective synthesis of tetrafluorinated hexose derivatives is described here, in both pyranose and furanose forms. In particular, the optimization of the enantioselective synthesis of the previously reported 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexopyranose 3, 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexofuranose 4, and 2,3-dideoxy-2,2,3,3-tetrafluoro-d-erythro-hexopyranose 5 is described as is the synthesis of two novel sugar derivatives, 3,4-dideoxy-3,3,4,4-tetrafluoro-d-threo-hexopyranose 6 and 3,4-dideoxy-3,3,4,4-tetrafluoro-d-erythro-hexopyranose 7. The key step of all syntheses is a perfluoroalkyl lithium-mediated C-C bond formation, either intramolecular or intermolecular, which proceeds in good to excellent yields. NMR and X-ray crystallographic analyses of the tetrafluorinated methyl pyranoside derivatives confirm their (4)C1 conformation. PMID:27014960

  15. Enantioselective construction of remote quaternary stereocentres

    NASA Astrophysics Data System (ADS)

    Mei, Tian-Sheng; Patel, Harshkumar H.; Sigman, Matthew S.

    2014-04-01

    Small molecules that contain all-carbon quaternary stereocentres--carbon atoms bonded to four distinct carbon substituents--are found in many secondary metabolites and some pharmaceutical agents. The construction of such compounds in an enantioselective fashion remains a long-standing challenge to synthetic organic chemists. In particular, methods for synthesizing quaternary stereocentres that are remote from other functional groups are underdeveloped. Here we report a catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted-alkenyl alcohols with aryl boronic acids. This method provides direct access to quaternary all-carbon-substituted β-, γ-, δ-, ɛ- or ζ-aryl carbonyl compounds, because the unsaturation of the alkene is relayed to the alcohol, resulting in the formation of a carbonyl group. The scope of the process also includes incorporation of pre-existing stereocentres along the alkyl chain, which links the alkene and the alcohol, in which the stereocentre is preserved. The method described allows access to diverse molecular building blocks containing an enantiomerically enriched quaternary centre.

  16. Noncovalent Substrate-Directed Enantioselective Heck Reactions: Synthesis of S- and P-Stereogenic Heterocycles.

    PubMed

    de Azambuja, Francisco; Carmona, Rafaela C; Chorro, Tomaz H D; Heerdt, Gabriel; Correia, Carlos Roque D

    2016-08-01

    S- and P-Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-flask reaction conditions. Several five-membered aryl- sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process. PMID:27273079

  17. Enantioselective Synthesis of Spirocyclohexadienones by NHC-Catalyzed Formal [3+3] Annulation Reaction of Enals.

    PubMed

    Yetra, Santhivardhana Reddy; Mondal, Santigopal; Mukherjee, Subrata; Gonnade, Rajesh G; Biju, Akkattu T

    2016-01-01

    The enantioselective synthesis of pyrazolone-fused spirocyclohexadienones was demonstrated by the reaction of α,β-unsaturated aldehydes with α-arylidene pyrazolinones under oxidative N-heterocyclic carbene (NHC)catalysis. This atom-economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all-carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC-catalyzed generation of chiral α,β-unsaturated acyl azoliums from enals, and base-mediated tandem generation of dienolate/enolate intermediates from pyrazolinones. PMID:26487242

  18. BIOACCUMULATION AND ENANTIOSELECTIVE BIOTRANSFORMATION OF FIPRONIL AND SELECTED CONAZOLE FUNGICIDES

    EPA Science Inventory

    In this research, dietary accumulation and enantioselective biotransformation were determined for rainbow trout (Oncorhynchus mykiss) exposed separately to the phenylpyrazole insecticide fipronil and to a series of selected conazole fungicides. Bioaccumulation of each pesticide ...

  19. Turinese stereochemistry: Eligio Perucca's enantioselectivity and Primo Levi's asymmetry.

    PubMed

    Kahr, Bart; Bing, Yonghong; Kaminsky, Werner; Viterbo, Davide

    2009-01-01

    A reputation restored: Eligio Perucca (see photo) first observed the enantioselective adsorption of a racemic mixture to a chiral crystal (NaClO(3)) in Turin in 1919. However, this milestone in enantioselective chemistry and chiroptics went unnoticed. Identified previously as a coward who refused in 1941 to supervise the research of the budding stereochemist Primo Levi because of the race laws, Perucca was opposed to the fascist regime. PMID:19266531

  20. Salen Promoted Enantioselective Nazarov Cyclizations of Activated and Unactivated Dienones

    PubMed Central

    2013-01-01

    A novel class of chiral 5,5′-di(2,4,6-trialkyl)aryl salen-metal complexes have been developed and shown to catalyze highly enantioselective Nazarov cyclization reactions, giving rise to cyclopentenoids in 90:10–98:2 er. Significantly, the catalysts also promote, for the first time, highly enantioselective Nazarov reactions of “unactivated” dienones, producing hydrindenone products having in place three contiguous chiral centers. PMID:23506509

  1. Enantioselective Hydrogenation of Diarylmethanimines for Synthesis of Chiral Diarylmethylamines.

    PubMed

    Kong, Duanyang; Li, Meina; Zi, Guofu; Hou, Guohua; He, Yong

    2016-08-01

    An enantioselective hydrogenation of N-substituted diarylmethanimines under mild conditions has been first realized by using an iridium catalyst with a chiral f-spiroPhos ligand. This method provides an efficient access to the asymmetric synthesis of a variety of chiral diarylmethylamines and their derivatives with excellent enantioselectivities (up to 99.4% ee) and high turnover numbers (TON up to 4000). PMID:27410993

  2. Enantioselective Nazarov Cyclization Catalyzed by a Cinchona Alkaloid Derivative

    PubMed Central

    Huang, Yu-Wen; Frontier, Alison J.

    2015-01-01

    Nucleophilic catalysts for a 1,6 addition/Nazarov cyclization/elimination sequence were evaluated for their ability to induce enantioselectivity in the electrocyclization step. Of the tertiary amines examined, it was found that a cinchona alkaloid derivative was able to generate substituted 5-hydroxy γ-methylene cyclopentenones with excellent enantioselectivity. The study results suggest that successful cyclization depends upon the ability of the dienyl diketone substrate to readily adopt an s-cis conformation. PMID:26085696

  3. Rhodium(II)-catalyzed enantioselective synthesis of troponoids.

    PubMed

    Murarka, Sandip; Jia, Zhi-Jun; Merten, Christian; Daniliuc, Constantin-G; Antonchick, Andrey P; Waldmann, Herbert

    2015-06-22

    We report a rhodium(II)-catalyzed highly enantioselective 1,3-dipolar cycloaddition reaction between the carbonyl moiety of tropone and carbonyl ylides to afford troponoids in good to high yields with excellent enantioselectivity. We demonstrate that α-diazoketone-derived carbonyl ylides, in contrast to carbonyl ylides derived from diazodiketoesters, undergo [6+3] cycloaddition reactions with tropone to yield the corresponding bridged heterocycles with excellent stereoselectivity. PMID:25959033

  4. Enantioselective recognition at mesoporous chiral metal surfaces

    PubMed Central

    Wattanakit, Chularat; Côme, Yémima Bon Saint; Lapeyre, Veronique; Bopp, Philippe A.; Heim, Matthias; Yadnum, Sudarat; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2014-01-01

    Chirality is widespread in natural systems, and artificial reproduction of chiral recognition is a major scientific challenge, especially owing to various potential applications ranging from catalysis to sensing and separation science. In this context, molecular imprinting is a well-known approach for generating materials with enantioselective properties, and it has been successfully employed using polymers. However, it is particularly difficult to synthesize chiral metal matrices by this method. Here we report the fabrication of a chirally imprinted mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and chiral template molecules. The porous platinum retains a chiral character after removal of the template molecules. A matrix obtained in this way exhibits a large active surface area due to its mesoporosity, and also shows a significant discrimination between two enantiomers, when they are probed using such materials as electrodes. PMID:24548992

  5. Recent advances in enantioselective gold catalysis.

    PubMed

    Zi, Weiwei; Dean Toste, F

    2016-08-01

    Interest in homogeneous gold catalysis has undergone a marked increase. As strong yet air- and moisture-tolerant π-acids, cationic gold(i) complexes have been shown to catalyze diverse transformations of alkenes, alkynes and allenes, opening new opportunities for chemical synthesis. The development of efficient asymmetric variants is required in order to take full advantage of the preparative potential of these transformations. During the last few years, the chemical community has achieved tremendous success in the area. This review highlights the updated progress (2011-2015) in enantioselective gold catalysis. The discussion is classified according to the π-bonds activated by gold(i), in an order of alkynes, allenes and alkenes. Other gold activation modes, such as σ-Lewis acid catalyzed reactions and transformations of diazo compounds are also discussed. PMID:26890605

  6. Absolute enantioselective separation: optical activity ex machina.

    PubMed

    Bielski, Roman; Tencer, Michal

    2005-11-01

    The paper describes methodology of using three independent macroscopic factors affecting molecular orientation to accomplish separation of a racemic mixture without the presence of any other chiral compounds, i. e., absolute enantioselective separation (AES) which is an extension of a concept of applying these factors to absolute asymmetric synthesis. The three factors may be applied simultaneously or, if their effects can be retained, consecutively. The resulting three mutually orthogonal or near orthogonal directors constitute a true chiral influence and their scalar triple product is the measure of the chirality of the system. AES can be executed in a chromatography-like microfluidic process in the presence of an electric field. It may be carried out on a chemically modified flat surface, a monolithic polymer column made of a mesoporous material, each having imparted directional properties. Separation parameters were estimated for these media and possible implications for the natural homochirality are discussed. PMID:16342798

  7. Catalytic Enantioselective α,β,γ-Trioxygenation.

    PubMed

    Chen, Jason S; Abeykoon, Gayan A

    2015-12-18

    Applying a catalytic enantioselective aldehyde α-oxygenation condition to an enal substrate led to the discovery of the first α,β,γ-trifunctionalization cascade of enals. Under optimal conditions, a tryptophan-derived imidazolidinone catalyst in fluorinated aromatic solvents provided α,β,γ-trioxyaldehydes in up to 51% isolated yield (average of 80% yield per oxygenation step) and 85:15 er. Substitution at the δ position was tolerated, but not at the α, β, or γ positions. The reaction proceeded through initial TEMPO incorporation at the γ position, and rapid racemization of this intermediate, reversible conjugate addition of water, followed by TEMPO incorporation at the α position to set all three stereocenters with double dynamic kinetic resolution. PMID:26651079

  8. Expanding the scope of Metal-Free enantioselective allylic substitutions: Anthrones

    PubMed Central

    Ceban, Victor; Tauchman, Jiří; Meazza, Marta; Gallagher, Greg; Light, Mark E.; Gergelitsová, Ivana; Veselý, Jan; Rios, Ramon

    2015-01-01

    The highly enantioselective asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with anthrones is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and excellent enantioselectivities. PMID:26592555

  9. Enantioselective Reduction of Ketones and Imines Catalyzed by (CN-Box)Re(V)-Oxo Complexes

    PubMed Central

    Nolin, Kristine A.; Ahn, Richard W.; Kobayashi, Yusuke; Kennedy-Smith, Joshua J.

    2012-01-01

    The development and application of chiral, non-racemic Re(V)-oxo complexes to the enantioselective reduction of prochiral ketones is described. In addition to the enantioselective reduction of prochiral ketones, we report the application of these complexes to (1) a tandem Meyer-Schuster rearrangement/reduction to access enantioenriched allylic alcohols and (2) the enantioselective reduction of imines. PMID:20623567

  10. An enantioselective formal synthesis of montelukast sodium.

    PubMed

    Bollikonda, Satyanarayana; Mohanarangam, Saravanan; Jinna, Rajender Reddy; Kandirelli, Venkata Kiran Kumar; Makthala, Laxman; Sen, Saikat; Chaplin, David A; Lloyd, Richard C; Mahoney, Thomas; Dahanukar, Vilas Hareshwar; Oruganti, Srinivas; Fox, Martin E

    2015-04-17

    A formal synthesis of the antiasthma drug montelukast sodium is described, wherein the key chiral diol intermediate was accessed with greater convergence of the C-C bond-forming steps as compared to previous routes. Improved synthetic efficiency was achieved by deploying homogeneous metal-based catalysis in two pivotal steps. In the first, a tandem Mizoroki-Heck reaction and double-bond isomerization between a previously known allyl alcohol intermediate and a hindered 2-(2-halophenyl)propan-2-ol secured direct access to the 3-(2-(2-hydroxypropan-2-yl)phenyl)-1-phenylpropan-1-one moiety in the product. In the second step, asymmetric hydrogenation of the ketone functionality in the Mizoroki-Heck reaction product provided a convenient method to introduce the benzylic alcohol chiral center and obtain the desired chiral diol precursor of montelukast sodium. A detailed catalyst screening led to the identification of ((R)-Xyl-BINAP)((R,R)-DPEN)RuCl2 as a catalyst that afforded an enantioselectivity of 99% ee in the hydrogenation step on a multigram lab scale at a molar substrate:catalyst loading of 5000:1. PMID:25807000

  11. Enantioselective analysis of ketone bodies in patients with beta-ketothiolase deficiency, medium-chain acyl coenzyme A dehydrogenase deficiency and ketonemic vomiting.

    PubMed

    Heil, M; Podebrad, F; Prado, E; Beck, T; Mosand, A; Sewell, A C; Böhles, H; Lehnert, W

    2000-03-10

    Enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC-MS) is a valuable tool for the differentiation of enantiomers from complex matrices when present in trace amounts. The separation of chiral compounds provides further information on the diagnosis of diseases, and on normal and abnormal biochemical pathways. The formation of the normal urinary metabolite 3-hydroxy-2-methylbutanoic acid (HMBA), excreted in abnormally high amounts in beta-ketothiolase deficiency, is not absolutely clarified. Metabolic pathways involving this metabolite are isoleucine catabolism, as well as presumably beta-oxidation of fatty acids and ketogenesis. The latter two pathways are distinguishable in their enantioselectivity. Enantioselective analysis gives further information on interfering metabolic pathways and the selectivity of the enzyme(s) forming HMBA. Different ratios of the stereoisomers of HMBA in control urine samples and patients with beta-ketothiolase deficiency were detected. Analogous to HMBA urinary 3-hydroxybutanoic acid (HBA) was investigated in several diseases. The formation of HBA and HMBA is expected to result from the same or similar metabolic pathways. Differences in the enantiomeric ratio of HMBA may originate from the enantioselectivity of different enzyme systems. PMID:10755375

  12. A Catalytic, Enantioselective Formal Synthesis of (+)-Dichroanone and (+)-Taiwaniaquinone H

    PubMed Central

    2015-01-01

    A catalytic, enantioselective formal synthesis of (+)-dichroanone and (+)-taiwaniaquinone H is reported. The all-carbon quaternary stereocenter was constructed by asymmetric conjugate addition catalyzed by a palladium(II) (S)-tert-butylpyridinooxazoline complex. The unexpected formation of a [3.2.1] bicyclic intermediate required the identification of a new route. Analysis of the Hammett constants for para-substituted arenes enabled the rational design of a highly enantioselective conjugate addition substrate that led to the completion of the formal synthesis. PMID:25489925

  13. A Divergent Enantioselective Strategy for the Synthesis of Griseusins

    PubMed Central

    Zhang, Yinan; Ye, Qing; Wang, Xiachang; She, Qing-Bai; Thorson, Jon S.

    2015-01-01

    The first enantioselective total synthesis of griseusin A, griseusin C, 4′-deacetyl-griseusin A, and two non-native counterparts in 11–14 steps is reported. This strategy highlights a key hydroxy-directed C–H olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies. PMID:26230189

  14. Aryl bromides as inexpensive starting materials in the catalytic enantioselective arylation of aryl aldehydes: the additive TMEDA enhances the enantioselectivity.

    PubMed

    Yang, Yong-Xin; Liu, Yue; Zhang, Lei; Jia, Yan-E; Wang, Pei; Zhuo, Fang-Fang; An, Xian-Tao; Da, Chao-Shan

    2014-11-01

    We used aryl bromides as inexpensive starting materials to enantioselectively arylate aldehydes in one pot. Aryl bromides readily transfer aryls to aryllithiums with n-butyllithium, successively to triarylaluminums with aluminum chloride, and then to aryltitaniums with titanium isopropoxide. Finally aryltitaniums arylate aldehydes catalyzed by (S)-H8-BINOL-Ti(Oi-Pr)2 in excellent yields and enantioselectivities. The additive TMEDA evidently suppresses the racemic background reaction promoted by LiCl generated from salt metathesis. This procedure represents a cost-effective and operationally convenient method for enantioenriched diarylmethanols. PMID:25279967

  15. Catalytic Enantioselective Desymmetrization Reactions to All-Carbon Quaternary Stereocenters.

    PubMed

    Zeng, Xing-Ping; Cao, Zhong-Yan; Wang, Yu-Hui; Zhou, Feng; Zhou, Jian

    2016-06-22

    This Review summarizes the advances in the construction of all-carbon quaternary stereocenters via catalytic enantioselective desymmetrization of prochiral and meso-compounds, highlights the power and potential of this strategy in the total synthesis of natural products and biologically active compounds, and outlines the synthetic opportunities still available. PMID:27251100

  16. Enantioselective Claisen rearrangements with a hydrogen-bond donor catalyst.

    PubMed

    Uyeda, Christopher; Jacobsen, Eric N

    2008-07-23

    N,N'-Diphenylguanidinium ion associated with the noncoordinating BArF counterion is shown to be an effective catalyst for the [3,3]-sigmatropic rearrangement of a variety of substituted allyl vinyl ethers. Highly enantioselective catalytic Claisen rearrangements of ester-substituted allyl vinyl ethers are then documented using a new C2-symmetric guanidinium ion derivative. PMID:18576616

  17. Whole cells in enantioselective reduction of benzyl acetoacetate

    PubMed Central

    Ribeiro, Joyce Benzaquem; Ramos, Aline de Souza; Lopes, Raquel de Oliveira; da Silva, Gabriela Veloso Vieira; de Souza, Rodrigo Octavio Mendonça Alves

    2014-01-01

    The β-ketoester benzyl acetoacetate was enantioselectively reduced to benzyl (S)-3-hydroxybutanoate by seven microorganism species. The best result using free cells was obtained with the yeast Hansenula sp., which furnished 97% ee and 85% of conversion within 24 h. After immobilization in calcium alginate spheres, K.marxianus showed to be more stable after 2 cycles of reaction. PMID:25477927

  18. Catalytic, Enantioselective, Intramolecular Carbosulfenylation of Olefins. Preparative and Stereochemical Aspects

    PubMed Central

    Denmark, Scott E.; Jaunet, Alex

    2014-01-01

    The first catalytic, enantioselective, intramolecular carbosulfenylation of isolated alkenes with aromatic nucleophiles is described. The combination of N-phenylsulfenylphthalimide, a chiral selenophosphoramide derived from BINAM, and ethanesulfonic acid as a co-catalytic Brønsted acid induced an efficient and selective cyclofunctionalization of various alkenes (aliphatic and aromatic) tethered to a 3,4-methylenedioxyphenyl ring. Under these conditions, 6-phenylthio-5,6,7,8-tetrahydronaphthalenes are formed diastereospecifically in good yields (50–92%) and high enantioselectivities (71:29 – 97:3 er). E-Alkenes reacted much more rapidly and with much higher selectivity than Z-alkenes, whereas electron rich alkenes reacted more rapidly but with comparable selectivity to electron-neutral alkenes and electron deficient alkenes. The Brønsted acid played a critical role in effecting reproducible enantioselectivity. A model for the origin of enantioselectivity and the dependence of rate and selectivity on alkene structure is proposed along with a rationale for the site selectivity in reactions with mono-activated arene nucleophiles. PMID:24328051

  19. Tunable P-Chiral Bisdihydrobenzooxaphosphole Ligands for Enantioselective Hydroformylation.

    PubMed

    Tan, Renchang; Zheng, Xin; Qu, Bo; Sader, C Avery; Fandrick, Keith R; Senanayake, Chris H; Zhang, Xumu

    2016-07-15

    Air-stable and tunable chiral bisdihydrobenzooxaphosphole ligands (BIBOPs) were employed in rhodium-catalyzed asymmetric hydroformylation of various terminal olefins with excellent conversions (>99%), moderate-to-excellent enantioselectivities (up to 95:5 er), and branched to linear ratios (b:l) of up to 400. PMID:27333435

  20. Loop grafting of Bacillus subtilis lipase A: inversion of enantioselectivity.

    PubMed

    Boersma, Ykelien L; Pijning, Tjaard; Bosma, Margriet S; van der Sloot, Almer M; Godinho, Luís F; Dröge, Melloney J; Winter, Remko T; van Pouderoyen, Gertie; Dijkstra, Bauke W; Quax, Wim J

    2008-08-25

    Lipases are successfully applied in enantioselective biocatalysis. Most lipases contain a lid domain controlling access to the active site, but Bacillus subtilis Lipase A (LipA) is a notable exception: its active site is solvent exposed. To improve the enantioselectivity of LipA in the kinetic resolution of 1,2-O-isopropylidene-sn-glycerol (IPG) esters, we replaced a loop near the active-site entrance by longer loops originating from Fusarium solani cutinase and Penicillium purpurogenum acetylxylan esterase, thereby aiming to increase the interaction surface for the substrate. The resulting loop hybrids showed enantioselectivities inverted toward the desired enantiomer of IPG. The acetylxylan esterase-derived variant showed an inversion in enantiomeric excess (ee) from -12.9% to +6.0%, whereas the cutinase-derived variant was improved to an ee of +26.5%. The enantioselectivity of the cutinase-derived variant was further improved by directed evolution to an ee of +57.4%. PMID:18721749

  1. A Green Enantioselective Aldol Condensation for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Bennett, George D.

    2006-01-01

    A number of laboratory exercises for the organic chemistry curriculum that emphasize enantioselective synthesis of the aldol condensation which involves the proline-catalyzed condensation between acetone and isobutyraldehyde are explored. The experiment illustrates some of the trade-offs involved in green chemistry like the use of acetone in large…

  2. Asymmetric Total Synthesis of (-)-Englerin A through Catalytic Diastereo- and Enantioselective Carbonyl Ylide Cycloaddition.

    PubMed

    Hanari, Taiki; Shimada, Naoyuki; Kurosaki, Yasunobu; Thrimurtulu, Neetipalli; Nambu, Hisanori; Anada, Masahiro; Hashimoto, Shunichi

    2015-08-10

    An asymmetric total synthesis of the guaiane sesquiterpene (-)-englerin A, a potent and selective inhibitor of the growth of renal cancer cell lines, was accomplished. The basis of the approach is a highly diastereo- and enantioselective carbonyl ylide cycloaddition with an ethyl vinyl ether dipolarophile under catalysis by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], [Rh2 (S-TCPTTL)4 ], to construct the oxabicyclo[3.2.1]octane framework with concomitant introduction of the oxygen substituent at C9 on the exo-face. Another notable feature of the synthesis is ruthenium tetraoxide-catalyzed chemoselective oxidative conversion of C9 ethyl ether to C9 acetate. PMID:26179743

  3. Enantioselective Total Synthesis of (−)-Citrinadin A and Revision of its Stereochemical Structure

    PubMed Central

    Bian, Zhiguo; Marvin, Christopher C.; Martin, Stephen F.

    2013-01-01

    The first enantioselective total synthesis of (−)-citrinadin A has been accomplished in 20 steps from commercially available materials via an approach that minimizes refunctionalization and protection/deprotection operations. The cornerstone of this synthesis features an asymmetric vinylogous Mannich addition of a dienolate to a chiral pyridinium salt to set the initial chiral center. A sequence of substrate-controlled reactions, including a highly stereoselective epoxidation/ring opening sequence and an oxidative rearrangement of an indole to furnish a spirooxindole, are then used to establish the remaining stereocenters in the pentacyclic core of (−)-citrinadin A. The successful synthesis of citrinadin A led to a revision of the stereochemical structure of the core substructure of the citrinadins. PMID:23837457

  4. Concise Enantioselective Total Synthesis of Cardiotonic Steroids 19-Hydroxysarmentogenin and Trewianin Aglycone.

    PubMed

    Kaplan, Will; Khatri, Hem Raj; Nagorny, Pavel

    2016-06-01

    The expedient and scalable approach to cardiotonic steroids carrying oxygenation at the C11- and C19-positions has been developed and applied to the total asymmetric synthesis of steroids 19-hydroxysarmentogenin and trewianin aglycone as well as to the assembly of the panogenin core. This new approach features enantioselective organocatalytic oxidation of an aldehyde, diastereoselective Cu(OTf)2-catalyzed Michael reaction/tandem aldol cyclizations, and one-pot reduction/transposition reactions allowing a rapid (7 linear steps) assembly of a functionalized cardenolide skeleton. The ability to quickly set this steroidal core with preinstalled functional handles and diversity elements eliminates the need for difficult downstream functionalizations and substantially improves the accessibility to the entire class of cardenolides and their derivatives for biological evaluation. PMID:27232585

  5. Enantioselective total synthesis of callipeltoside A: two approaches to the macrolactone fragment

    PubMed Central

    Evans, David A.; Burch, Jason D.; Hu, Essa; Jaeschke, Georg

    2012-01-01

    The enantioselective total synthesis of callipeltoside A is described. Two syntheses of the macrolactone subunit are included: the first relies upon an Ireland–Claisen rearrangement to generate the trisubstituted olefin geometry and the second utilizes an enantioselective vinylogous aldol reaction for this purpose. Enantioselective syntheses of the sugar and chlorocyclopropane side chain fragments are also disclosed. The relative and absolute stereochemistry of this natural product was determined by fragment coupling with the two enantiomers of the side chain fragment. PMID:22859865

  6. Isolation of lipase producer and its performance in enantioselective hydrolysis of glycidyl butyrate.

    PubMed

    Jia, Shi-Ying; Xu, Jian-He; Li, Qing Shan; Yu, Jun Tang

    2003-01-01

    A racemic glycidyl butyrate resolving strain, preliminarily identified as a Rhizopus sp., had been isolated from soil. Its extracellular lipase was found to enantioselectively hydrolyze the (S)-enantiomer of the chiral ester, with optimal activities at pH 5.3 and 42 degrees C. Higher enantioselectivity of the enzyme was observed at lower temperatures, while the best enantioselectivity was obtained at pH 5.5-6.0, with an E value (enantiomeric ratio) of 57. PMID:12495206

  7. Highly Enantioselective Rhodium-Catalyzed Addition of Arylboroxines to Simple Aryl Ketones: Efficient Synthesis of Escitalopram.

    PubMed

    Huang, Linwei; Zhu, Jinbin; Jiao, Guangjun; Wang, Zheng; Yu, Xingxin; Deng, Wei-Ping; Tang, Wenjun

    2016-03-24

    Highly enantioselective additions of arylboroxines to simple aryl ketones have been achieved for the first time with a Rh/(R,R,R,R)-WingPhos catalyst, thus providing a range of chiral diaryl alkyl carbinols with excellent ee values and yields. (R,R,R,R)-WingPhos has been proven to be crucial for the high reactivity and enantioselectivity. The method has enabled a new, concise, and enantioselective synthesis of the antidepressant drug escitalopram. PMID:26933831

  8. Enantioselective induction of cytotoxicity by o,p'-DDD in PC12 cells: implications of chirality in risk assessment of POPs metabolites.

    PubMed

    Wang, Cui; Li, Zhuoyu; Zhang, Quan; Zhao, Meirong; Liu, Weiping

    2013-04-16

    The increased release of chiral persistent organic pollutants (POPs) into the environment has resulted in more attention to the role of enantioselectivity in the fate and ecotoxicological effects of these compounds. Although the enantioselectivity of chiral POPs has been considered in previous studies, little effort has been expended to discern the enantiospecific effects of chiral POPs metabolites, which may impede comprehensive risk assessments of these chemicals. In the present study, o,p'-DDD, the chiral metabolite of o,p'-DDT, was used as a model chiral metabolite. First, a preferential chiral separation at 100% ethanol was employed to obtain a pure enantiomer. The enantioselective cytotoxicity of o,p'-DDD in rat cells (PC12) was evaluated by detecting activation of the cellular apoptosis and oxidative stress systems and microarray analysis. We have documented for the first time that R-(+)-o,p'-DDD increases apoptosis by selectively disturbing the oxidative system (enzymes and molecules) and regulating the transcription of Aven, Bid, Cideb and Tp53. By comparing the data from the present study to data derived from the parent compound, we concluded that the R-enantiomer is the more detrimental stereostructure for both o,p'-DDT and o,p'-DDD. This observed stereostructural effect is in line with the structure-activity relationship formulated at other structural levels. Biological activities of the chiral metabolites are likely to occur in the same absolute configuration between chiral POPs and their metabolites provided that they have the similar stereostructures. PMID:23485034

  9. A novel enantioselective synthesis of 6H-dibenzopyran derivatives by combined palladium/norbornene and cinchona alkaloid catalysis.

    PubMed

    Xu, Di; Dai, Li; Catellani, Marta; Motti, Elena; Della Ca', Nicola; Zhou, Zhiming

    2015-02-28

    Organometallic and organo-catalysts are cooperatively at work in the enantioselective synthesis of dibenzopyran derivatives; palladium/norbornene and a cinchona alkaloid base guarantee good yields and satisfactory enantioselectivities in a one-pot reaction. PMID:25584921

  10. Enantioselective synthesis of fluorinated branched allylic compounds via Ir-catalyzed allylations of functionalized fluorinated methylene derivatives.

    PubMed

    Zhang, Hongbo; Chen, Jiteng; Zhao, Xiao-Ming

    2016-08-14

    Enantioselective introduction of the functionalized monofluorinated methylenes into the allylic fragment under Ir catalysis has been realized, which gave the fluorinated branched allyl products in good to high yields with excellent regio- and enantioselectivities. PMID:27383920

  11. Enantioselective tandem reaction over a site-isolated bifunctional catalyst.

    PubMed

    Xu, Jianyou; Cheng, Tanyu; Zhang, Kun; Wang, Ziyun; Liu, Guohua

    2016-05-21

    Construction of a site-isolated heterogeneous catalyst to realize the compatibility of bimetallic complexes for a feasible tandem reaction is a significant challenge in heterogeneous asymmetric catalysis. Herein, taking advantage of yolk-shell-structured mesoporous silica, we assemble an active site-isolated bifunctional catalyst through assembly of organopalladium-functionality into silicate channels as an outer shell and chiral organoruthenium-functionality onto silicate yolk as an inner core, realizing the one-pot enantioselective tandem reaction from Pd-catalyzed Sonogashira coupling to Ru-catalyzed asymmetric transfer hydrogenation. As presented in this study, this tandem Sonogashira coupling-asymmetric transfer hydrogenation of haloacetophenones and arylacetylenes affords various chiral conjugated alkynols with high yields and up to 99% enantioselectivity. Moreover, a catalyst can also be recovered easily and recycled repeatedly, making it an interesting feature in a practical organic transformation. PMID:27063335

  12. Enantioselective Rhodium-Catalyzed Atom-Economical Macrolactonization.

    PubMed

    Ganss, Stephanie; Breit, Bernhard

    2016-08-01

    A highly attractive route toward macrolactones, which form the cyclic scaffold of a multitude of diverse natural compounds, is described. Although many chemical approaches to this structural motif have been explored, an asymmetric variant of the cyclization is unprecedented. Herein we present an enantioselective macrolactonization through an intramolecular atom-economical rhodium-catalyzed coupling of ω-allenyl-substituted carboxylic acids. The use of a modified diop ligand, chiral DTBM-diop, led to high enantioselectivity (up to 93 % ee). The reaction tolerated a large variety of functionalities, including α,β-unsaturated carboxylic acids and depsipeptides, and provided the desired macrocycles with very high enantio- and diastereoselectivity. PMID:27383766

  13. Dynamic control of chirality in phosphine ligands for enantioselective catalysis

    PubMed Central

    Zhao, Depeng; Neubauer, Thomas M.; Feringa, Ben L.

    2015-01-01

    Chirality plays a fundamental role in biology and chemistry and the precise control of chirality in a catalytic conversion is a key to modern synthesis most prominently seen in the production of pharmaceuticals. In enantioselective metal-based catalysis, access to each product enantiomer is commonly achieved through ligand design with chiral bisphosphines being widely applied as privileged ligands. Switchable phosphine ligands, in which chirality is modulated through an external trigger signal, might offer attractive possibilities to change enantioselectivity in a catalytic process in a non-invasive manner avoiding renewed ligand synthesis. Here we demonstrate that a photoswitchable chiral bisphosphine based on a unidirectional light-driven molecular motor, can be used to invert the stereoselectivity of a palladium-catalysed asymmetric transformation. It is shown that light-induced changes in geometry and helicity of the switchable ligand enable excellent selectivity towards the racemic or individual enantiomers of the product in a Pd-catalysed desymmetrization reaction. PMID:25806856

  14. Enantioselective hydrolysis of naproxen ethyl ester catalyzed by monoclonal antibodies.

    PubMed

    Shi, Zhen-Dan; Yang, Bing-Hui; Zhao, Jing-Jing; Wu, Yu-Lin; Ji, Yong-Yong; Yeh, Ming

    2002-07-01

    This report described that a hapten of racemic phosphonate 3 designed as the mimic of the transition state of hydrolysis of naproxen ethyl ester was successfully synthesized from easily available 2-acetyl-6-methoxy-naphthalene 5. Then BALB/C mice were immunized and one of the monoclonal catalytic antibodies, N116-27, which enantioselectively accelerated the hydrolysis of the R-(-)-naproxen ethyl ester was given. The Michaelis-Menton parameter for the catalyzed reaction was K(M)=6.67 mM and k(cat)/k(uncat)=5.8 x 10(4). This enantioselective result was explained by the fact that the R-isomer of rac-hapten was more immunogenic than the S-isomer. PMID:11983513

  15. Enantioselective iron-catalysed O-H bond insertions

    NASA Astrophysics Data System (ADS)

    Zhu, Shou-Fei; Cai, Yan; Mao, Hong-Xiang; Xie, Jian-Hua; Zhou, Qi-Lin

    2010-07-01

    The ready availability, low price and environmentally benign character of iron mean that it is an ideal alternative to precious metals in catalysis. Recent growth in the number of iron-catalysed reactions reported reflects an increasing demand for sustainable chemistry. Only a limited number of chiral iron catalysts have been reported and these have, in general, proven less enantioselective than other transition-metal catalysts, thus limiting their appeal. Here, we report that iron complexes of spiro-bisoxazoline ligands are highly efficient catalysts for asymmetric O-H bond insertion reactions. These complexes catalyse insertions into the O-H bond of a wide variety of alcohols and even water, with exceptional enantioselectivities under mild reaction conditions. The selectivities surpass those obtained with other transition-metal catalysts. This study should inspire and encourage the use of iron instead of traditional precious metals in the development of greener catalysts for catalytic asymmetric synthesis.

  16. Structure Elucidation of Nigricanoside A Through Enantioselective Total Synthesis

    PubMed Central

    Chen, Jie; Koswatta, Panduka; DeBergh, J. Robb; Fu, Peng; Pan, Ende; MacMillan, John B.; Ready, Joseph M.

    2016-01-01

    Nigricanoside A was isolated from green alga, and its dimethyl ester was found to display potent cytotoxicity. Its scarcity prevented a full structure elucidation, leaving total synthesis as the only means to determine its relative and absolute stereochemistry and to explore its biological activity. Here we assign the stereochemistry of the natural product through enantioselective total synthesis and provide initial studies of its cytotoxicity. PMID:26877863

  17. Rhodium-Catalyzed Enantioselective Arylation of Aliphatic Imines.

    PubMed

    Kato, Naoya; Shirai, Tomohiko; Yamamoto, Yasunori

    2016-06-01

    Chiral rhodium(I)-catalyzed highly enantioselective arylation of aliphatic N-sulfonyl aldimines with arylboronic acids has been developed. This transformation is achieved by the use of a rhodium/bis(phosphoramidite) catalyst to give enantiomerically enriched α-branched amines (up to 99 % ee). In addition, this system enables efficient synthesis of (+)-NPS R-568 and Cinacalcet which are calcimimetic agents. PMID:27119262

  18. Cobalt-Catalyzed Enantioselective Vinylation of Activated Ketones and Imines.

    PubMed

    Huang, Yuan; Huang, Rui-Zhi; Zhao, Yu

    2016-05-25

    We present here an unprecedented cobalt-catalyzed enantioselective vinylation of α-ketoesters, isatins, and imines to deliver a range of synthetically useful allylic alcohols and amines in high enantiopurity. This method employs commercially available and easy to handle catalysts and reagents and exhibits a high degree of practicality. The efficiency, selectivity, and operational simplicity of this catalytic system coupled with the substrate generality render this method a valuable tool in organic synthesis. PMID:27139596

  19. Enantioselective hydrolyzation and photolyzation of dufulin in water

    PubMed Central

    2013-01-01

    Background Dufulin is a novel, highly effective antiviral agent that activatives systemic acquired resistance of plants. This compound is widely used in China to prevent and control viral diseases in tobacco, vegetable and rice. Dufulin can treat plants infected by the tobacco mosaic virus and the cucumber mosaic virus. However, the achiral analysis and residue determination of dufulin remain underdeveloped because of its high enantioselectivity rates and high control costs. The enantioselectivity of an antiviral compound is an important factor that should be considered when studying the effect of chiral pesticides on the environment. The enantioselective degradation of dufulin in water remains an important objective in pesticide science. Results The configuration of dufulin enantiomers was determined in this study based on its circular dichroism spectra. The S-(+)-dufulin and R-(−)-dufulin enantiomers were separated and identified using an amylose tris-(3,5-dimethylphenylcarbamate) chiral column by normal phase high-performance liquid chromatography. The degradation of the rac-dufulin racemate and its separate enantiomers complied with first-order reaction kinetics and demonstrated acceptable linearity. The enantioselective photolysis of rac-dufulin allowed for the faster degradation of R-(−)-dufulin, as compared with S-(+)-dufulin. However, S-(+)-dufulin was hydrolyzed faster than its antipode. Conclusion The photolysation and hydrolyzation of dufulin in water samples normally complied with the first-order kinetics and demonstrated acceptable linearity (R2>0.66). A preferential photolysation of the R-(−)-enantiomer was observed in water samples. Moreover, the S-(+)-enantiomer was hydrolyzed faster than its antipode. PMID:23680125

  20. Rhodium-Catalyzed Enantioselective Hydroamination of Alkynes with Indolines

    PubMed Central

    Chen, Qing-An; Chen, Zhiwei; Dong, Vy M.

    2016-01-01

    The hydroamination of internal alkynes via tandem rhodium-catalysis gives branched N-allylic indolines with high regio- and enantioselectivity. An acid-switch provides access to the linear isomer in preference to the branched isomer by an isomerization mechanism. Mechanistic studies suggest formation of an allene intermediate, which undergoes hydroamination to generate allylic amines instead of the enamine or imine products typically observed in alkyne hydroaminations. PMID:26107923

  1. Catalytic, Enantioselective Sulfenylation of Ketone-Derived Enoxysilanes

    PubMed Central

    2015-01-01

    A catalytic, enantioselective, Lewis base-catalyzed α-sulfenylation of silyl enol ethers has been developed. To avoid acidic hydrolysis of the silyl enol ether substrates, a sulfenylating agent that did not require additional Brønsted acid activation, namely N-phenylthiosaccharin, was developed. Three classes of Lewis bases—tertiary amines, sulfides, and selenophosphoramides—were identified as active catalysts for the α-sulfenylation reaction. Among a wide variety of chiral Lewis bases in all three classes, only chiral selenophosphoramides afforded α-phenylthio ketones in generally high yield and with good enantioselectivity. The selectivity of the reaction does not depend on the size of the silyl group but is highly sensitive to the double bond geometry and the bulk of the substituents on the double bond. The most selective substrates are those containing a geminal bulky substituent on the enoxysilane. Computational analysis revealed that the enantioselectivity arises from an intriguing interplay among sterically guided approach, distortion energy, and orbital interactions. PMID:25192220

  2. Cyclodextrin Derivatives as Chiral Supramolecular Receptors for Enantioselective Sensing

    PubMed Central

    Shahgaldian, Patrick; Pieles, Uwe

    2006-01-01

    In view of the chiral nature of many bio-molecules (and all bio-macromolecules), most of therapeutically active compounds which target these molecules need to be chiral and “good handed” to be effective. In addition to asymmetric synthetic and separation methodologies, enantioselective chemical sensors, able to distinguish between two enantiomers of the same molecule, are of relevance. In order to design these sensing tools, two major classes of enantioselective layers have been developed. The first is based on molecularly imprinted polymers which are produced (polymerized) in the presence of their target, thus the polymeric material keep in “memory” the size and the shape of this molecule and the system could be used for sensing (not reviewed here). The second approach makes use of sensitive layers containing chiral macrocyclic receptors able of stereoselective molecular recognition; these receptors are mainly based on cyclodextrins. In this contribution, are reviewed achievements in the use of native or chemically modified cyclodextrins for chiral sensing purposes (at interfaces). Potentialities of other chiral macrocycles based on calixarenes, calix-resorcinarenes or crown-ethers as supramolecular receptors for enantioselective sensing are discussed.

  3. Covalently immobilized lipase on aminoalkyl-, carboxy- and hydroxy-multi-wall carbon nanotubes in the enantioselective synthesis of Solketal esters.

    PubMed

    Zniszczoł, Aurelia; Herman, Artur P; Szymańska, Katarzyna; Mrowiec-Białoń, Julita; Walczak, Krzysztof Z; Jarzębski, Andrzej; Boncel, Sławomir

    2016-06-01

    Aiming at the preparation of efficient, stable on storage and recyclable nanobiocatalysts for enantioselective transesterification, alkaline lipase from Pseudomonas fluorescens was covalently immobilized (up to 8.5wt.%) on functionalized multi-wall carbon nanotubes (f-MWCNTs). f-MWCNTs were synthesized via: (a) (2+1)-cycloaddition of a nitrene to the C-sp(2) nanotube walls (3.2mmolg(-1), a novel synthetic approach) and, (b) oxidative treatments, i.e. Fenton reagent (3.5mmolg(-1)) and nitrating mixture (2.5mmolg(-1)), yielding aminoalkyl-, hydroxyl- and carboxyl-MWCNTs, respectively. Amino- and epoxy- functionalized mesoporous silica (f-SBA-15) were used as the reference supports. Transesterification of vinyl n-butyrate by racemic Solketal with a chromatographically (GC) traced kinetics was selected as the model reaction. The studies revealed that different chemical functionalization of morphologically identical nanotube supports led to various enzyme loadings, catalytic activities and enantioselectivities. MWCNT-NH2-based nanobiocatalyst was found to be the most active composite among all of the tested systems (yield 20%, t=0.5h, 1321Ug(-1)), i.e. 12 times more active than the native enzyme. In turn, lipase immobilized on MWCNT-COOH emerged as the most enantioselective system (ex aequo with SBA-NH2) (eeR=74%, t=0.5h at yield of 3-5%). The activity of the MWCNT-NH2-based nanobiocatalyst after 8 cycles of transesterification dropped to 60% of its initial value, whereas for SBA-NH2-based composite remained unchanged. Importantly, stability on storage was fully maintained for all MWCNT-based nanobiocatalysts or even 'extra-enhanced' for MWCNT-OH. PMID:27178796

  4. Redox-triggered C-C coupling of alcohols and vinyl epoxides: diastereo- and enantioselective formation of all-carbon quaternary centers via tert-(hydroxy)-prenylation.

    PubMed

    Feng, Jiajie; Garza, Victoria J; Krische, Michael J

    2014-06-25

    Iridium catalyzed primary alcohol oxidation triggers reductive C-O bond cleavage of isoprene oxide to form aldehyde-allyliridium pairs that combine to form products of tert-(hydroxy)-prenylation, a motif found in >2000 terpenoid natural products. Curtin-Hammett effects are exploited to enforce high levels of anti-diastereo- and enantioselectivity in the formation of an all-carbon quaternary center. The present redox-triggered carbonyl additions occur in the absence of stoichiometric byproducts, premetalated reagents, and discrete alcohol-to-aldehyde redox manipulations. PMID:24915473

  5. Asymmetric synthesis of trifluoromethylated amines via catalytic enantioselective isomerization of imines.

    PubMed

    Wu, Yongwei; Deng, Li

    2012-09-01

    A new approach toward the asymmetric synthesis of optically active trifluoromethylated amines was enabled by an unprecedented, highly enantioselective catalytic isomerization of trifluoromethyl imines with a new chiral organic catalyst. Not only aryl but also alkyl trifluoromethylated amines could be obtained in high enantioselectivities. PMID:22906148

  6. Enantioselective sulfoxidation reaction catalyzed by a G-quadruplex DNA metalloenzyme.

    PubMed

    Cheng, Mingpan; Li, Yinghao; Zhou, Jun; Jia, Guoqing; Lu, Sheng-Mei; Yang, Yan; Li, Can

    2016-07-26

    Enantioselective sulfoxidation reaction is achieved for the first time by a DNA metalloenzyme assembled with the human telomeric G-quadruplex DNA and Cu(ii)-4,4'-bimethyl-2,2'-bipyridine complex, and the mixed G-quadruplex architectures are responsible for the catalytic enantioselectivity and activity. PMID:27359255

  7. Quinine-thiourea catalyzed enantioselective hydrophosphonylation of trifluoromethyl 2(1H)-quinazolinones.

    PubMed

    Xie, Hexin; Song, Aiguo; Zhang, Xinshuai; Chen, Xiaobei; Li, Hao; Sheng, Chunquan; Wang, Wei

    2013-01-30

    An organocatalytic enantioselective addition reaction of cyclic ketoimines with phosphites has been developed for the first time. The process, catalyzed by Soós' quinine thiourea, affords synthetically and medicinally interesting enantioenriched trifluoromethyl dihydroquinazolinones in high yields and with high enantioselectivities. PMID:23248060

  8. Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

    PubMed Central

    Jang, Hee Seung; Kim, Yubin

    2016-01-01

    Summary Chiral binaphthyl-modified squaramide-catalyzed enantioselective addition of diphenyl phosphonate to ketimines derived from isatins has been achieved. This method affords practical and efficient access to chiral 3-amino-3-phosphonyl-substituted oxindole derivatives in high yields with excellent enantioselectivities (up to 99% ee). PMID:27559405

  9. Enantioselective carbenoid insertion into C(sp3)–H bonds

    PubMed Central

    Santiago, J V

    2016-01-01

    Summary The enantioselective carbenoid insertion into C(sp3)–H bonds is an important tool for the synthesis of complex molecules due to the high control of enantioselectivity in the formation of stereogenic centers. This paper presents a brief review of the early issues, related mechanistic studies and recent applications on this chemistry area. PMID:27340479

  10. Highly enantioselective Henry reactions of aromatic aldehydes catalyzed by an amino alcohol-copper(II) complex.

    PubMed

    Qin, Dan-Dan; Lai, Wen-Han; Hu, Di; Chen, Zheng; Wu, An-An; Ruan, Yuan-Ping; Zhou, Zhao-Hui; Chen, Hong-Bin

    2012-08-20

    Amino alcohol-Cu(II) catalyst: Highly enantioselective Henry reactions between aromatic aldehydes and nitromethane have been developed. The reactions were catalyzed by an easily available and operationally simple amino alcohol-copper(II) catalyst. In total, 38 substrates were tested and the R-configured products were obtained in good yields with excellent enantioselectivities. PMID:22791567

  11. Organocatalytic enantioselective desymmetrization of cyclic enones via phosphine promoted [3+2] annulations.

    PubMed

    Pinto, Nathalie; Retailleau, Pascal; Voituriez, Arnaud; Marinetti, Angela

    2011-01-21

    Phosphine catalyzed enantioselective [3+2] cyclizations on 4-substituted 2,6-diarylidenecyclohexanones and 2,4-diarylidene-bicyclo[3.1.0]hexan-3-ones take place with high diastereo- and enantioselectivity levels. The process affords spirocyclic compounds with excellent stereochemical control of up to five stereogenic centres. PMID:21063612

  12. Enantioselective acylation of silyl ketene acetals through fluoride anion-binding catalysis.

    PubMed

    Birrell, James A; Desrosiers, Jean-Nicolas; Jacobsen, Eric N

    2011-09-01

    A highly enantioselective acylation of silyl ketene acetals with acyl fluorides has been developed to generate useful α,α-disubstituted butyrolactone products. This transformation is promoted by a new thiourea catalyst and 4-pyrrolidinopyridine and represents the first example of enantioselective thiourea anion-binding catalysis with fluoride. PMID:21800916

  13. Enantioselective Selenocyclization via Dynamic Kinetic Resolution of Seleniranium Ions by Hydrogen-Bond Donor Catalysts

    PubMed Central

    2015-01-01

    Highly enantioselective selenocyclization reactions are promoted by the combination of a new chiral squaramide catalyst, a mineral acid, and an achiral Lewis base. Mechanistic studies reveal that the enantioselectivity originates from the dynamic kinetic resolution of seleniranium ions through anion-binding catalysis. PMID:25380129

  14. Organocatalytic Enantioselective Intramolecular Oxa-Michael Reaction of Enols: Synthesis of Chiral Isochromenes.

    PubMed

    Parhi, Biswajit; Gurjar, Jitendra; Pramanik, Suman; Midya, Abhisek; Ghorai, Prasanta

    2016-06-01

    An unprecedented enantioselective intramolecular oxa-Michael reaction of enols has been described. A squaramide-containing tertiary amine based bifunctional organocatalyst efficiently activates the o-homoformyl chalcones to provide the chiral isochromenes in moderate yields and good to excellent enantioselectivities. Further, late-stage functionalizations of the vinyl ether moiety of the chiral isochromene products have also been exemplified. PMID:27176883

  15. Amino Acid-Derived Bifunctional Phosphines for Enantioselective Transformations.

    PubMed

    Wang, Tianli; Han, Xiaoyu; Zhong, Fangrui; Yao, Weijun; Lu, Yixin

    2016-07-19

    Even though seminal reports on phosphine catalysis appeared in the 1960s, in the last few decades of the past century trivalent phosphines were viewed primarily as useful ligands for transition-metal-mediated processes. The 1990s saw revived interest in using phosphines in organic catalysis, but the key advances in asymmetric phosphine catalysis have all come within the past decade. The uniqueness of phosphine catalysis can be attributed to the high nucleophilicity of the phosphorus atom. In typical phosphine-catalyzed reactions, nucleophilic attacks of the phosphorus atom on electron-deficient multiple bonds create different reactive ylide-type intermediates. When such structurally diverse zwitterionic species react with a variety of suitable substrates, new reaction patterns are often discovered and a diverse array of reactions can be developed. In recent years, substantial progress has been made in the field of asymmetric phosphine catalysis; many new reactions have been discovered, and numerous enantioselective processes have been reported. However, we felt that powerful and versatile phosphine catalysts that can work for a wide range of asymmetric reactions are still lacking. We therefore set our goal to develop a family of easily derived phosphine catalysts that are efficient in asymmetric induction for a broad range of phosphine-mediated transformations. This Account describes our efforts in the past few years on the development of amino acid-based bifunctional phosphines and their applications to enantioselective processes. Building upon our previous success in primary-amine-mediated enamine catalysis, we first established that bifunctional phosphines could be readily prepared from amino acids. In most of our studies, we chose threonine as the key backbone for catalyst development, and threonine-based monoamino acid or dipeptide bifunctional phosphines have displayed remarkable stereochemical control. We began our investigations by demonstrating the

  16. Highly Enantioselective Formation of α-Allyl-α-Arylcyclopentanones via Pd-Catalysed Decarboxylative Asymmetric Allylic Alkylation.

    PubMed

    Akula, Ramulu; Doran, Robert; Guiry, Patrick J

    2016-07-11

    A highly enantioselective Pd-catalysed decarboxylative asymmetric allylic alkylation of cyclopentanone derived α-aryl-β-keto esters employing the (R,R)-ANDEN-phenyl Trost ligand has been developed. The product (S)-α-allyl-α-arylcyclopentanones were obtained in excellent yields and enantioselectivities (up to >99.9 % ee). This represents one of the most highly enantioselective formations of an all-carbon quaternary stereogenic center reported to date. This reaction was demonstrated on a 4.0 mmol scale without any deterioration of enantioselectivity and was exploited as the key enantioselective transformation in an asymmetric formal synthesis of the natural product (+)-tanikolide. PMID:27191198

  17. Substrate range and enantioselectivity of epoxidation reactions mediated by the ethene-oxidising Mycobacterium strain NBB4.

    PubMed

    Cheung, Samantha; McCarl, Victoria; Holmes, Andrew J; Coleman, Nicholas V; Rutledge, Peter J

    2013-02-01

    Mycobacterium strain NBB4 is an ethene-oxidising micro-organism isolated from estuarine sediments. In pursuit of new systems for biocatalytic epoxidation, we report the capacity of strain NBB4 to convert a diverse range of alkene substrates to epoxides. A colorimetric assay based on 4-(4-nitrobenzyl)pyridine) has been developed to allow the rapid characterisation and quantification of biocatalytic epoxide synthesis. Using this assay, we have demonstrated that ethene-grown NBB4 cells epoxidise a wide range of alkenes, including terminal (propene, 1-butene, 1-hexene, 1-octene and 1-decene), cyclic (cyclopentene, cyclohexene), aromatic (styrene, indene) and functionalised substrates (allyl alcohol, dihydropyran and isoprene). Apparent specific activities have been determined and range from 2.5 to 12.0 nmol min(-1) per milligram of cell protein. The enantioselectivity of epoxidation by Mycobacterium strain NBB4 has been established using styrene as a test substrate; (R)-styrene oxide is produced in enantiomeric excesses greater than 95%. Thus, the ethene monooxygenase of Mycobacterium NBB4 has a broad substrate range and promising enantioselectivity, confirming its potential as a biocatalyst for alkene epoxidation. PMID:22410742

  18. Remote Enantioselection Transmitted by an Achiral Peptide Nucleic Acid Backbone

    NASA Technical Reports Server (NTRS)

    Kozlov, Igor A.; Orgel, Leslie E.; Nielsen, Peter E.

    2000-01-01

    short homochiral segment of DNA into a PNA helix could have guaranteed that the next short segment of DNA to be incorporated would have the same handedness as the first. Once two segments of the same handedness were present, the probability that a third segment would have the same handedness would increase, and so on. Evolution could then slowly dilute out the PNA part. This scenario would ultimately allow the formation of a chiral oligonucleotide by processes that are largely resistant to enantiomeric crossinhibition. It is important to note that the ligation of homochiral dinucleotides on a nucleic acid template would probably be at least as enantiospecific as the reaction that we have studied. The disadvantage of using chiral monomers as components of a replicating system arises from the difficulty of generating a first long homochiral template from a racemic mixture of monomers, although results of experiments designed to overcome this difficulty by employing homochiral tetramers have been reported.l l The probability of obtaining a homochiral n-mer from achiral substrates is approximately 1P-I if the nontemplate-directed extension of the primer is not enantioselective. Hence, it would be very hard to get started with a homochiral 40-mer, for example. No such difficulty exists in a scenario that originates with an achiral genetic material and in which the incorporation of very few chiral monomers in this achiral background gradually progresses towards homochirality. It seems possible that some PNA sequences could act as catalysts, analogous to ribozymes, even though PNA lacks clear metal binding sites. Although such catalysts could not be enantioselective, the incorporation of as few as two chiral nucleotides could then impose chiral specificity on the system. Furthermore, such patch chimeras could help to bridge the gap in catalytic potential between PNA and RNA, while guaranteeing enantioselectivity.

  19. Enantioselective phytotoxicity and bioacitivity of the enantiomers of the herbicide napropamide.

    PubMed

    Qi, Yanli; Liu, Donghui; Zhao, Wenting; Liu, Chang; Zhou, Zhiqiang; Wang, Peng

    2015-11-01

    Enantioselectivity of chiral pesticide enantiomers should be taken into consideration in pesticide application and environmental risk assessment. The phytotoxicity of the enantiomers of napropamide to cucumber, soybean, and the bioactivity to the target weeds Poa annua and Festuca arundinacea have been studied in this work. To the nontarget crops, the influences of napropamide on the root, shoot, fresh weight, chlorophyll, superoxide dismutase (SOD) and catalase (CAT) activities and membrane lipid peroxides have been studied. (-)-Napropamide was more toxic than the racemate and (+)-napropamide to soybean and cucumber in terms of root, shoot and fresh weight. The content of chlorophyll was not affected by napropamide. The impacts on the activities of SOD, CAT and membrane lipid peroxides showed that napropamide could induce the oxidative stress and rac-napropamide caused a stronger oxidative damage to cucumber and soybean than (-)-napropamide and (+)-napropamide. For the target weeds, the influences of napropamide on root, shoot and fresh weight have been studied. (-)-Napropamid was more active to P. annua, while rac-napropamide was more active to F. arundinacea. To reduce environmental pollution and improve the effectiveness of chiral pesticide, single enantiomer should be developed and produced. This work may provide evidence for developing optical pure product. PMID:26615149

  20. Enantioselective copper-catalyzed carboetherification of unactivated alkenes.

    PubMed

    Bovino, Michael T; Liwosz, Timothy W; Kendel, Nicole E; Miller, Yan; Tyminska, Nina; Zurek, Eva; Chemler, Sherry R

    2014-06-16

    Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols which terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition-state calculations support a cis-oxycupration stereochemistry-determining step. PMID:24798697

  1. Permanent microporosity and enantioselective sorption in a chiral open framework.

    PubMed

    Bradshaw, Darren; Prior, Timothy J; Cussen, Edmund J; Claridge, John B; Rosseinsky, Matthew J

    2004-05-19

    A homochiral microporous material is presented. The phase has 47% permanently porous void volume and is shown to have >1 nm diameter pores with three-dimensional channels using probe molecule sorption. Enantioselective guest sorption is strongly dependent on guest size. The homochiral microporous phase was identified by reactive selection from a first-generation chiral but nonporous framework. Chiral permanent porosity is established by directional noncovalent interactions between framework-forming and nonframework forming components of the stable second-generation material, which become stronger upon loss of the guests from the pore system. PMID:15137776

  2. Low-Pressure Cobalt-Catalyzed Enantioselective Hydrovinylation of Vinylarenes.

    PubMed

    Movahhed, Sohajl; Westphal, Julia; Dindaroğlu, Mehmet; Falk, Anna; Schmalz, Hans-Günther

    2016-05-23

    An efficient and practical protocol for the enantioselective cobalt-catalyzed hydrovinylation of vinylarenes with ethylene at low (1.2 bar) pressure has been developed. As precatalysts, stable [L2 CoCl2 ] complexes are employed that are activated in situ with Et2 AlCl. A modular chiral TADDOL-derived phosphine-phosphite ligand was identified that allows the conversion of a broad spectrum of substrates, including heterocyclic vinylarenes and vinylferrocene, to smoothly afford the branched products with up to 99 % ee and virtually complete regioselectivity. Even polar functional groups, such as OH, NH2 , CN, and CO2 R, are tolerated. PMID:26998912

  3. Highly Enantioselective Iridium-Catalyzed Hydrogenation of Cyclic Enamides.

    PubMed

    Salomó, Ernest; Orgué, Sílvia; Riera, Antoni; Verdaguer, Xavier

    2016-07-01

    The MaxPHOX-Ir catalyst system provided the highest selectivity ever reported for the reduction of cyclic enamides derived from α- and β-tetralones. This result indicates that iridium catalysts are also proficient in reducing alkenes bearing metal-coordinating groups. In the present system, selectivity was pressure-dependent: In most cases, a decrease in the H2 pressure to 3 bar resulted in an increase in enantioselectivity. Moreover, the process can be carried out in environmentally friendly solvents, such as methanol and ethyl acetate, with no loss of selectivity. PMID:27186653

  4. Enantioselective Hydrosilylation of Imines Catalyzed by Chiral Zinc Acetate Complexes.

    PubMed

    Bezłada, Agata; Szewczyk, Marcin; Mlynarski, Jacek

    2016-01-01

    A series of zinc acetate complexes with optically pure diphenylethanediamine (DPEDA)-derived ligands have been employed as enantioselective catalyst for the hydrosilylation of various imines. High control of stereoselectivity (up to 97% ee) and excellent yields (up to 96%) were gained for a broad range of N-phosphinoylimines by using (R,R)-N,N'-dibenzyl-1,2-diphenylethane-1,2-diamine. This is the first successful application of an air-stable and environmentally friendly chiral Zn(OAc)2 complex instead of the previously used harmful diethylzinc in the asymmetric reduction of the C═N double bond. PMID:26667387

  5. Substitution of Val72 residue alters the enantioselectivity and activity of Penicillium expansum lipase.

    PubMed

    Tang, Lianghua; Su, Min; Zhu, Ling; Chi, Liying; Zhang, Junling; Zhou, Qiong

    2013-01-01

    Error-prone PCR was used to create more active or enantioselective variants of Penicillium expansum lipase (PEL). A variant with a valine to glycine substitution at residue 72 in the lid structure exhibited higher activity and enantioselectivity than those of wild-type PEL. Site-directed saturation mutagenesis was used to explore the sequence-function relationship and the substitution of Val72 of P. expansum lipase changed both catalytic activity and enantioselectivity greatly. The variant V72A, displayed a highest enantioselectivity enhanced to about twofold for the resolution of (R, S)-naproxen (E value increased from 104 to 200.7 for wild-type PEL and V72A variant, respectively). In comparison to PEL, the variant V72A showed a remarkable increase in specific activity towards p-nitrophenyl palmitate (11- and 4-fold increase at 25 and 35 °C, respectively) whereas it had a decreased thermostability. The results suggest that the enantioselective variant V72A could be used for the production of pharmaceutical drugs such as enantiomerically pure (S)-naproxen and the residue Val 72 of P. expansum lipase plays a significant role in the enantioselectivity and activity of this enantioselective lipase. PMID:22972595

  6. Infrared-thermographic screening of the activity and enantioselectivity of enzymes.

    PubMed

    Reetz, M T; Hermes, M; Becker, M H

    2001-05-01

    The infrared radiation caused by the heat of reaction of an enantioselective enzyme-catalyzed transformation can be detected by modern photovoltaic infrared (IR)-thermographic cameras equipped with focal-plane array detectors. Specifically, in the lipase-catalyzed enantioselective acylation of racemic 1-phenylethanol, the (R)- and (S)-substrates are allowed to react separately in the wells of microtiter plates, the (R)-alcohol showing hot spots in the IR-thermographic images. Thus, highly enantioselective enzymes can be identified at kinetic resolution. PMID:11414316

  7. Enantioselective and Regiodivergent Functionalization of N-Allylcarbamates by Mechanistically Divergent Multicatalysis.

    PubMed

    Richmond, Edward; Khan, Ismat Ullah; Moran, Joseph

    2016-08-22

    A pair of mechanistically divergent multicatalytic reaction sequences has been developed consisting of nickel-catalyzed isomerization of N-allylcarbamates and subsequent phosphoric-acid-catalyzed enantioselective functionalization of the resulting intermediates. By appropriate selection of reaction partners, in situ generated imines and ene-carbamates are mechanistically partitioned to yield opposing functionalized products. Formal α-functionalization to give protected α-arylamines is achieved upon enantioselective Friedel-Crafts reaction with arene nucleophiles, whereas formal β-functionalization is achieved upon reaction with diarylimine electrophiles in an enantioselective Povarov-[4+2] cycloaddition. PMID:27461524

  8. Enantioselective intermolecular cross Rauhut-Currier reactions of activated alkenes with acrolein.

    PubMed

    Zhou, Wei; Chen, Peng; Tao, Mengna; Su, Xiao; Zhao, Qingjie; Zhang, Junliang

    2016-06-18

    The enantioselective intermolecular cross Rauhut-Currier reaction of acrolein with active olefins has been a long-standing challenge because of the competitive MBH reaction and polymerization. Herein a highly enantioselective intermolecular cross Rauhut-Currier reaction of acrolein with 3-acyl acrylates and 2-ene-1,4-diones, which is enabled by newly designed Peng-Phos catalysts. This method is scalable and highly enantioselective (up to 96% ee). Several transformations of the R-C products are carried out to showcase the synthetic utility. PMID:27225510

  9. 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. PMID:22967461

  10. Enantioselective TADMAP-Catalyzed Carboxyl Migration Reactions for the Synthesis of Stereogenic Quaternary Carbon

    PubMed Central

    Shaw, Scott A.; Aleman, Pedro; Christy, Justin; Kampf, Jeff W.; Va, Porino

    2008-01-01

    The chiral, nucleophilic catalyst TADMAP (1) has been prepared from 3-lithio-4-dimethylamino-pyridine (5) and triphenylacetaldehyde (3), followed by acylation and resolution. TADMAP catalyzes the carboxyl migration of oxazolyl, furanyl, and benzofuranyl enol carbonates with good to excellent levels of enantioselection. The oxazole reactions are especially efficient, and are used to prepare chiral lactams (23) and lactones (30) containing a quaternary asymmetric carbon. TADMAP-catalyzed carboxyl migrations in the indole series are relatively slow and proceed with inconsistent enantioselectivity. Modeling studies (B3LYP/6-31G*) have been used in qualitative correlations of catalyst conformation, reactivity, and enantioselectivity. PMID:16417383

  11. Degradation of a commercial textile biocide with advanced oxidation processes and ozone.

    PubMed

    Arslan-Alaton, Idil

    2007-01-01

    The occurrence of significant amounts of biocidal finishing agents in the environment as a consequence of intensive textile finishing activities has become a subject of major public health concern and scientific interest only recently. In the present study, the treatment efficiency of selected, well-known advanced oxidation processes (Fenton, Photo-Fenton, TiO(2)/UV-A, TiO(2)/UV-A/H(2)O(2)) and ozone was compared for the degradation and detoxification of a commercial textile biocide formulation containing a 2,4,4'-trichloro-2'-hydroxydiphenyl ether as the active ingredient. The aqueous biocide solution was prepared to mimic typical effluent originating from the antimicrobial finishing operation (BOD(5,o) < or =5 mg/L; COD(o)=200 mg/L; DOC(o) (dissolved organic carbon)=58 mg/L; AOX(o) (adsorbable organic halogens)=48 mg/L; LC(50,o) (lethal concentration causing 50% death or immobilization in Daphnia magna)=8% v/v). Ozonation experiments were conducted at different ozone doses (500-900 mg/h) and initial pH (7-12) to assess the effect of ozonation on degradation (COD, DOC removal), dearomatization (UV(280) and UV(254) abatement), dechlorination (AOX removal) and detoxification (changes in LC(50)). For the Fenton experiments, the effect of varying ferrous iron catalyst concentrations and UV-A light irradiation (the Photo-Fenton process) was examined. In the heterogenous photocatalytic experiments, Degussa P25-type TiO(2) was used as the catalyst and the effect of reaction pH (3, 7 and 12) and H(2)O(2) addition on the photocatalytic treatment efficiency was examined. Although in the photochemical (i.e. Photo-Fenton, TiO(2)/UV-A and TiO(2)/UV-A/H(2)O(2)) experiments appreciably higher COD and DOC removal efficiencies were obtained, ozonation appeared to be equally effective to achieve dearomatization (UV(280) abatement) at all studied reaction pH. During ozonation of the textile biocide effluent, AOX abatement proceeded significantly faster than dearomatization and was

  12. Discovery of enantioselectivity of urea inhibitors of soluble epoxide hydrolase.

    PubMed

    Manickam, Manoj; Pillaiyar, Thanigaimalai; Boggu, PullaReddy; Venkateswararao, Eeda; Jalani, Hitesh B; Kim, Nam-Doo; Lee, Seul Ki; Jeon, Jang Su; Kim, Sang Kyum; Jung, Sang-Hun

    2016-07-19

    Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) in the metabolic pathway of arachidonic acid and has been considered as an important therapeutic target for chronic diseases such as hypertension, diabetes and inflammation. Although many urea derivatives are known as sEH inhibitors, the enantioselectivity of the inhibitors is not highlighted in spite of the stereoselective hydrolysis of EETs by sEH. In an effort to explore the importance of enantioselectivity in the urea scaffold, a series of enantiomers with the stereocenter adjacent to the urea nitrogen atom were prepared. The selectivity of enantiomers of 1-(α-alkyl-α-phenylmethyl)-3-(3-phenylpropyl)ureas showed wide range differences up to 125 fold with the low IC50 value up to 13 nM. The S-configuration with planar phenyl and small alkyl groups at α-position is crucial for the activity and selectivity. However, restriction of the free rotation of two α-groups with indan-1-yl or 1,2,3,4-tetrahydronaphthalen-1-yl moiety abolishes the selectivity between the enantiomers, despite the increase in activity up to 13 nM. The hydrophilic group like sulfonamido group at para position of 3-phenylpropyl motif of 1-(α-alkyl-α-phenylmethyl-3-(3-phenylpropyl)urea improves the activity as well as enantiomeric selectivity. All these ureas are proved to be specific inhibitor of sEH without inhibition against mEH. PMID:27092411

  13. Enantioselective degradation of metalaxyl in grape, tomato, and rice plants.

    PubMed

    Wang, Meiyun; Hua, Xiude; Zhang, Qing; Yang, Yu; Shi, Haiyan; Wang, Minghua

    2015-02-01

    Enantioselective biodegradation of chiral pesticide metalaxyl in grape, tomato, and rice plants under field conditions were studied. Metalaxyl enantiomers were completely separated with a resolution (Rs) of 5.01 by high-performance liquid chromatography (HPLC) based on a cellulose tris (3-chloro-4-methyl phenyl carbamate) chiral column (Lux Cellulose-2). Metalaxyl enantiomers from matrixes were extracted by acetonitrile and purged using Cleanert Alumina-A solid phase extraction (SPE). The linearity, recovery, precision, sensitivity, and matrix effect of the method were assessed. The result showed that significant stereoselectivity occurred in grape, tomato, and rice plants. In grape, (+)-S-metalaxyl with a half-life of 5.5 d degraded faster than (-)-R-metalaxyl with that of 6.9 d, and the enantiomer fraction (EF) value reached 0.37 at 21 d. The same enantioselectivity was observed in tomato, and the half-life was 2.2 d for the S-enantiomer and 3.0 d for the R-enantiomer. The EF values decreased from 0.49 of 0 d to 0.26 of 14 d. On the other hand, a preferential degradation of the R-form was found in rice plants, with an EF value of 0.70 at 14 d, and the corresponding half-life was 2.3 d for the R-form and 2.8 d for the S-form. PMID:25311959

  14. Enantioselective toxic effects of cyproconazole enantiomers against Chlorella pyrenoidosa.

    PubMed

    Zhang, Wenjun; Cheng, Cheng; Chen, Li; Di, Shanshan; Liu, Chunxiao; Diao, Jinling; Zhou, Zhiqiang

    2016-09-01

    Enantioselectivity in ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to Chlorella pyrenoidosa was studied. The 96h-EC50 values of rac- and the four enantiomers were 9.005, 6.616, 8.311, 4.290 and 9.410 mg/L, respectively. At the concentrations of 8 mg/L and 14 mg/L, the contents of pigments exposed in rac-, enantiomer-2 and 4 were higher than that exposed in enantiomer-1 and 3. The superoxide dismutase (SOD) and catalase (CAT) activity of algae exposed to enantiomer-1 and 3 was higher than that exposed to the rac-, enantiomer-2 and 4 at three levels. In addition, the malondialdehyde (MDA) concentrations in algae disposed with enantiomer-1 and 3 were increased remarkably at three levels. For the digestion experiment, the half-lives of four enantiomers in algae suspension were 28.06, 19.10, 21.13, 15.17 days, respectively. During the uptake experiment, the order of the concentrations of cyproconazole in algae cells was enantiomer-4, 2, 3 and 1. Based on these data, we concluded that ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to C. pyrenoidosa were enantioselective, and such enantiomeric differences must be taken into consideration when assessing the risk of cyproconazole to environment. PMID:27268794

  15. RNA-Cleaving DNA Enzymes with Altered Regio- or Enantioselectivity

    NASA Technical Reports Server (NTRS)

    Ordoukhanian, Phillip; Joyce, Gerald F.

    2002-01-01

    In vitro evolution methods were used to obtain DNA enzymes that cleave either a 2',5' - phosphodiester following a wibonucleotide or a 3',5' -phosphodiester following an L-ribonucleotide. Both enzymes can operate in an intermolecular reaction format with multiple turnover. The DNA enzyme that cleaves a 2',5' -phosphodiester exhibits a k(sub cat) of approx. 0.01/ min and catalytic efficiency, k(sub cat)/k(sub m) of approx. 10(exp 5)/ M min. The enzyme that cleaves an L-ribonudeotide is about 10-fold slower and has a catalytic efficiency of approx. 4 x 10(exp 5)/ M min. Both enzymes require a divalent metal cation for their activity and have optimal catalytic rate at pH 7-8 and 35-50 C. In a comparison of each enzyme s activity with either its corresponding substrate that contains an unnatural ribonudeotide or a substrate that instead contains a standard ribonucleotide, the 2',5' -phosphodiester-deaving DNA enzyme exhibited a regioselectivity of 6000- fold, while the L-ribonucleotide-cleaving DNA enzyme exhibited an enantioselectivity of 50-fold. These molecules demonstrate how in vitro evolution can be used to obtain regio- and enantioselective catalysts that exhibit specificities for nonnatural analogues of biological compounds.

  16. Enantioselective Total Synthesis of (−)-Acutumine

    PubMed Central

    Li, Fang; Tartakoff, Samuel S.; Castle, Steven L.

    2009-01-01

    An account of the total synthesis of the tetracyclic alkaloid (−)-acutumine is presented. A first-generation approach to the spirocyclic subunit was unsuccessful due to incorrect regioselectivity in a radical cyclization. However, this work spawned a second-generation strategy in which the spirocycle was fashioned via a radical–polar crossover reaction. This process merged an intramolecular radical conjugate addition with an enolate hydroxylation, and created two stereocenters with excellent diastereoselectivity. The reaction was promoted by irradiation with a sunlamp, and a ditin reagent was required for aryl radical formation. These facts suggest that the substrate may function as a sensitizer, thereby facilitating homolytic cleavage of the ditin reagent. The propellane motif of the target was then installed via annulation of a pyrrolidine ring onto the spirocycle. The sequence of reactions used included a phenolic oxidation, an asymmetric ketone allylation mediated by Nakamura’s chiral allylzinc reagent, an anionic oxy-Cope rearrangement, a one-pot ozonolysis–reductive amination, and a Lewis acid promoted cyclization of an amine onto an α,β-unsaturated dimethyl ketal. Further studies of the asymmetric ketone allylation demonstrated the ability of the Nakamura reagent to function well in a mismatched situation. A TiCl4-catalyzed regioselective methyl enol etherification of a 1,3-diketone completed the synthesis. PMID:19904909

  17. Enantioselective cyclization of enamide-ynes and application to the synthesis of the kopsifoline core

    PubMed Central

    Corkey, Britton K.; Heller, Stephen T.; Wang, Yi-Ming

    2013-01-01

    We report the palladium-catalyzed enantioselective cyclization of 1,6-enamidynes to form spirocyclic ring systems. We applied this methodology to the concise synthesis of the skeletal core of the kopsifoline alkaloids. PMID:23772095

  18. CAPILLARY ELECTROPHORESIS FOR ENANTIOMER SEPARATION AND MEASUREMENT OF ENANTIOSELECTIVITY OF CHIRAL POLLUTANTS IN THE ENVIRONMENT

    EPA Science Inventory

    Chiral pollutants exist as 2 species, -- enantiomers - that have identical physical and chemical properties except when they interact with enzymes or other chiral molecules; then they usually react selectively. This enantioselectivity results in different rates of microbial trans...

  19. Residue Val237 is critical for the enantioselectivity of Penicillium expansum lipase.

    PubMed

    Tang, Lianghua; Su, Min; Chi, Liying; Zhang, Junling; Zhang, Huihui; Zhu, Ling

    2014-03-01

    The shape of the hydrophobic tunnel leading to the active site of Penicillium expansum lipase (PEL) was redesigned by single-point mutations, in order to better understand enzyme enantioselectivity towards naproxen. A variant with a valine-to-glycine substitution at residue 237 exhibited almost no enantioselectivity (E = 1.1) compared with that (E = 104) of wild-type PEL. The function of the residue, Val237, in the hydrophobic tunnel was further analyzed by site-directed mutagenesis. For each of these variants a significant decrease of enantioselectivity (E < 7) was observed compared with that of wild-type enzyme. Further docking result showed that Val237 plays the most important role in stabilizing the correct orientation of (R)-naproxen. Overall, these results indicate that the residue Val237 is the key amino acid residue maintaining the enantioselectivity of the lipase. PMID:24338160

  20. MEASUREMENT OF THE ENANTIOSELECTIVE TRANSFORMATION OF CHIRAL POLLUTANTS BY CAPILLARY ELECTROPHORESIS

    EPA Science Inventory

    The enantiomers of chiral pollutants have identical physical and chemical properties but usually react selectively with enzymes or other chiral molecules. This enantioselectivity results in different rates of microbial transformation and idfferences in toxicity of the 2 (or more...

  1. USE OF CAPILLARY ELECTROPHORESIS TO MEASURE THE ENANTIOSELECTIVE TRANSFORMATIONS OF CHIRAL ENVIRONMENTAL POLLUTANTS

    EPA Science Inventory

    The enantiomers of chiral pollutants have identical physical and chemical properties but usually react selectively with enzymes or other chiral molecules. This enantioselectivity results in different rates of microbial transformation and differences in toxicity of the 2 (or more...

  2. ENANTIOSELECTIVE TRANSFORMATION OF CHIRAL PCBS AND THE INSECTICIDE FIPRONIL IN NATURAL ANOXIC SEDIMENTS

    EPA Science Inventory

    In this study, we examined the microbial transformation of two chiral PCB congeners and the insecticide fipronil in natural sediment microcosms. The specific goals of the study were to identify biotransformation pathways and determine if enantioselective microbial transformation ...

  3. Enantioselective synthesis of 4H-pyranonaphthoquinones via sequential squaramide and silver catalysis.

    PubMed

    Kaya, Uğur; Chauhan, Pankaj; Hack, Daniel; Deckers, Kristina; Puttreddy, Rakesh; Rissanen, Kari; Enders, Dieter

    2016-01-28

    An enantioselective one-pot Michael addition/hydroalkoxylation reaction between 2-hydroxy-1,4-naphthoquinones and alkyne-tethered nitroalkenes catalyzed by a cinchona-derived squaramide and a silver(I) salt has been developed. The sequential protocol provides a direct access to 4H-pyranonaphthoquinones in moderate to very good yields and good to excellent enantioselectivities at a very low catalyst loading (0.5 mol%) of the squaramide. PMID:26660230

  4. A Unified Approach for the Enantioselective Synthesis of the Brominated Chamigrene Sesquiterpenes.

    PubMed

    Burckle, Alexander J; Vasilev, Vasil H; Burns, Noah Z

    2016-09-12

    The brominated chamigrene sesquiterpenes constitute a large subclass of bromocyclohexane-containing natural products, yet no general enantioselective strategy for the synthesis of these small molecules exists. Herein we report a general strategy for accessing this family of secondary metabolites, including the enantioselective synthesis of (-)-α- and (-)-ent-β-bromochamigrene, (-)-dactylone, and (+)-aplydactone. Access to these molecules is enabled by a stereospecific bromopolyene cyclization initiated by the solvolysis of an enantiomerically enriched vicinal bromochloride. PMID:27506430

  5. Direct enantioselective conjugate addition of carboxylic acids with chiral lithium amides as traceless auxiliaries.

    PubMed

    Lu, Ping; Jackson, Jeffrey J; Eickhoff, John A; Zakarian, Armen

    2015-01-21

    Michael addition is a premier synthetic method for carbon-carbon and carbon-heteroatom bond formation. Using chiral dilithium amides as traceless auxiliaries, we report the direct enantioselective Michael addition of carboxylic acids. A free carboxyl group in the product provides versatility for further functionalization, and the chiral reagent can be readily recovered by extraction with aqueous acid. The method has been applied in the enantioselective total synthesis of the purported structure of pulveraven B. PMID:25562717

  6. Asymmetric Hydrogenation of Seven-Membered C=N-containing Heterocycles and Rationalization of the Enantioselectivity.

    PubMed

    Balakrishna, Bugga; Bauzá, Antonio; Frontera, Antonio; Vidal-Ferran, Anton

    2016-07-18

    Iridium(I) complexes with phosphine-phosphite ligands efficiently catalyze the enantioselective hydrogenation of diverse seven-membered C=N-containing heterocyclic compounds (eleven examples; up to 97 % ee). The P-OP ligand L3, which incorporates an ortho-diphenyl substituted octahydrobinol phosphite fragment, provided the highest enantioselectivities in the hydrogenation of most of the heterocyclic compounds studied. The observed stereoselection was rationalized by means of DFT calculations. PMID:27333576

  7. Highly enantioselective conjugate addition of malononitrile to 2-enoylpyridines with bifunctional organocatalyst.

    PubMed

    Molleti, Nagaraju; Rana, Nirmal K; Singh, Vinod K

    2012-09-01

    An efficient enantioselective conjugate addition of malononitrile to a range of β-substituted 2-enoylpyridines catalyzed by cinchona alkaloid-based bifunctional urea catalysts has been developed. Both enantiomers of the products could be achieved with the same level of enantioselectivity by using pseudoenantiomeric catalysts in up to 97% ee and in excellent yields. One of the enantioenriched products has been transformed to a highly functionalized piperidone derivative. PMID:22920458

  8. Enantioselective Intermolecular Cyclopropanations for the Synthesis of Chiral Pyrimidine Carbocyclic Nucleosides.

    PubMed

    Xie, Ming-Sheng; Zhou, Peng; Niu, Hong-Ying; Qu, Gui-Rong; Guo, Hai-Ming

    2016-09-01

    A direct route to chiral cyclopropylpyrimidine carbocyclic nucleoside analogues has been reported via highly enantioselective intermolecular cyclopropanation reactions of N1-vinylpyrimidines with α-diazoesters. With chiral ruthenium(II)-phenyloxazoline complex (2 mol %) as the catalyst, cyclopropyl pyrimidine nucleoside analogues could be obtained in good yields (71-96% yields) with high levels of diastereo- and enantioselectivities (10:1 to >20:1 dr and 96-99% ee) in 1 min. PMID:27526779

  9. Enantioselective isothiourea-catalysed trans-dihydropyridinone synthesis using saccharin-derived ketimines: scope and limitations.

    PubMed

    Stark, Daniel G; Young, Claire M; O'Riordan, Timothy J C; Slawin, Alexandra M Z; Smith, Andrew D

    2016-09-14

    The catalytic enantioselective synthesis of a range of trans-dihydropyridinones from aryl-, heteroaryl- and alkenylacetic acids and saccharin-derived ketimines with good to excellent stereocontrol (15 examples, up to >95 : 5 dr, up to >99 : 1 er) is reported. After extensive optimisation, HyperBTM proved the optimal isothiourea catalyst for this transformation at -78 °C, giving trans-dihydropyridones with generally excellent levels of diastereo- and enantioselectivity. PMID:27492887

  10. Quinine-catalyzed highly enantioselective cycloannulation of o-quinone methides with malononitrile.

    PubMed

    Adili, Alafate; Tao, Zhong-Lin; Chen, Dian-Feng; Han, Zhi-Yong

    2015-02-28

    2-Amino-3-cyano-4H-chromenes show great potential as novel anticancer agents. Here we report a quinine-catalyzed highly enantioselective formal 4 + 2 cycloaddition of ortho-quinone methides and malononitrile, providing a unique approach to 4-arylvinyl, 4-aryl and 4-vinyl 2-amino-3-cyano-4H-chromenes with excellent yields and enantioselectivities. Moreover, this reaction can be performed in up to 6 mmol scale without any noticeable loss of yield and stereoselectivity. PMID:25592961

  11. Enantiodivergent Combination of Natural Product Scaffolds Enabled by Catalytic Enantioselective Cycloaddition.

    PubMed

    Xu, Hao; Golz, Christopher; Strohmann, Carsten; Antonchick, Andrey P; Waldmann, Herbert

    2016-06-27

    An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst. PMID:27193834

  12. Acetylphosphonate as a Surrogate of Acetate or Acetamide in Organocatalyzed Enantioselective Aldol Reactions

    PubMed Central

    Guang, Jie; Guo, Qunsheng

    2012-01-01

    Highly enantioselective aldol reactions of acetylphosphonates and activated carbonyl compounds was realized with cinchona alkaloid derived catalysts, in which the acetylphosphonate was directly used as an enolate precursor for the first time. The aldol product obtained was converted in situ to its corresponding ester or amide through methanolysis or aminolysis. The overall process may be viewed as formal highly enantioselective acetate or acetamide aldol reactions, which are very difficult to achieve directly with organocatalytic methods. PMID:22650245

  13. Enantioselective CuH-Catalyzed Reductive Coupling of Aryl Alkenes and Activated Carboxylic Acids.

    PubMed

    Bandar, Jeffrey S; Ascic, Erhad; Buchwald, Stephen L

    2016-05-11

    A new method for the enantioselective reductive coupling of aryl alkenes with activated carboxylic acid derivatives via copper hydride catalysis is described. Dual catalytic cycles are proposed, with a relatively fast enantioselective hydroacylation cycle followed by a slower diastereoselective ketone reduction cycle. Symmetrical aryl carboxyclic anhydrides provide access to enantioenriched α-substituted ketones or alcohols with excellent stereoselectivity and functional group tolerance. PMID:27121395

  14. Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

    PubMed Central

    Liu, Yiyang; Liniger, Marc; McFadden, Ryan M; Roizen, Jenny L; Malette, Jacquie; Reeves, Corey M; Behenna, Douglas C; Seto, Masaki; Kim, Jimin; Mohr, Justin T; Virgil, Scott C

    2014-01-01

    Summary Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of “classic” natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge. PMID:25383121

  15. Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation.

    PubMed

    Liu, Yiyang; Liniger, Marc; McFadden, Ryan M; Roizen, Jenny L; Malette, Jacquie; Reeves, Corey M; Behenna, Douglas C; Seto, Masaki; Kim, Jimin; Mohr, Justin T; Virgil, Scott C; Stoltz, Brian M

    2014-01-01

    Pd-catalyzed enantioselective alkylation in conjunction with further synthetic elaboration enables the formal total syntheses of a number of "classic" natural product target molecules. This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods will impact both academic and industrial settings, where the synthesis of stereogenic quaternary carbons is a continuing challenge. PMID:25383121

  16. Engineering an enantioselective amine oxidase for the synthesis of pharmaceutical building blocks and alkaloid natural products.

    PubMed

    Ghislieri, Diego; Green, Anthony P; Pontini, Marta; Willies, Simon C; Rowles, Ian; Frank, Annika; Grogan, Gideon; Turner, Nicholas J

    2013-07-24

    The development of cost-effective and sustainable catalytic methods for the production of enantiomerically pure chiral amines is a key challenge facing the pharmaceutical and fine chemical industries. This challenge is highlighted by the estimate that 40-45% of drug candidates contain a chiral amine, fueling a demand for broadly applicable synthetic methods that deliver target structures in high yield and enantiomeric excess. Herein we describe the development and application of a "toolbox" of monoamine oxidase variants from Aspergillus niger (MAO-N) which display remarkable substrate scope and tolerance for sterically demanding motifs, including a new variant, which exhibits high activity and enantioselectivity toward substrates containing the aminodiphenylmethane (benzhydrylamine) template. By combining rational structure-guided engineering with high-throughput screening, it has been possible to expand the substrate scope of MAO-N to accommodate amine substrates containing bulky aryl substituents. These engineered MAO-N biocatalysts have been applied in deracemization reactions for the efficient asymmetric synthesis of the generic active pharmaceutical ingredients Solifenacin and Levocetirizine as well as the natural products (R)-coniine, (R)-eleagnine, and (R)-leptaflorine. We also report a novel MAO-N mediated asymmetric oxidative Pictet-Spengler approach to the synthesis of (R)-harmicine. PMID:23808566

  17. Flexible enantioselectivity of tryptophanase attributable to benzene ring in heterocyclic moiety of d-tryptophan.

    PubMed

    Shimada, Akihiko; Ozaki, Haruka

    2012-01-01

    The invariance principle of enzyme enantioselectivity must be absolute because it is absolutely essential to the homochiral biological world. Most enzymes are strictly enantioselective, and tryptophanase is one of the enzymes with extreme absolute enantioselectivity for L-tryptophan. Contrary to conventional knowledge about the principle, tryptophanase becomes flexible to catalyze D-tryptophan in the presence of diammonium hydrogenphosphate. Since D-amino acids are ordinarily inert or function as inhibitors even though they are bound to the active site, the inhibition behavior of D-tryptophan and several inhibitors involved in this process was examined in terms of kinetics to explain the reason for this flexible enantioselectivity in the presence of diammonium hydrogenphosphate. Diammonium hydrogenphosphate gave tryptophanase a small conformational change so that D-tryptophan could work as a substrate. As opposed to other D-amino acids, D-tryptophan is a very bulky amino acid with a benzene ring in its heterocyclic moiety, and so we suggest that this structural feature makes the catalysis of D-tryptophan degradation possible, consequently leading to the flexible enantioselectivity. The present results not only help to understand the mechanism of enzyme enantioselectivity, but also shed light on the origin of homochirality. PMID:25382167

  18. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

    NASA Astrophysics Data System (ADS)

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-02-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1-S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.

  19. Enantioselectivity in tebuconazole and myclobutanil non-target toxicity and degradation in soils.

    PubMed

    Li, Yuanbo; Dong, Fengshou; Liu, Xingang; Xu, Jun; Han, Yongtao; Zheng, Yongquan

    2015-03-01

    Tebuconazole and myclobutanil are two widely used triazole fungicides, both comprising two enantiomers with different fungicidal activity. However, their non-target toxicity and environmental behavior with respect to enantioselectivity have received limited attention. In the present study, tebuconazole and myclobutanil enantiomers were isolated and used to evaluate the occurrence of enantioselectivity in their acute toxicity to three non-target organisms (Scenedesmus obliquus, Daphnia magna, and Danio rerio). Significant differences were found: R-(-)-tebuconazole was about 1.4-5.9 times more toxic than S-(+)-tebuconazole; rac-myclobutanil was about 1.3-6.1 and 1.4-7.3 more toxic than (-)-myclobutanil and (+)-myclobutanil, respectively. Enantioselectivity was further investigated in terms of fungicide degradation in seven soil samples, which were selected to cover a broad range of soil properties. In aerobic or anaerobic soils, the S-(+)-tebuconazole degraded faster than R-(-)-tebuconazole, and the enantioselectivity showed a correlation with soil organic carbon content. (+)-Myclobutanil was preferentially degraded than (-)-myclobutanil in aerobic soils, whereas both enantiomers degraded at similar rates in anaerobic soils. Apparent correlations of enantioselectivity with soil pH and soil texture were observed for myclobutanil under aerobic conditions. In addition, both fungicides were configurationally stable in soils, i.e., no enantiomerization was found. Enantioselectivity may be a common phenomenon in both aquatic toxicity and biodegradation of chiral triazole fungicides, and this should be considered when assessing ecotoxicological risks of these compounds in the environment. PMID:25475972

  20. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes.

    PubMed

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-01-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1-S3) at neutral pH indicated that the "back-to-back" bisCD complex CuL(1) favoured higher catalytic efficiency and more pronounced enantioselectivity than the "face-to-face" complex CuL(2). The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL(1), which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL(1), even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics. PMID:26916830

  1. Catalytic, Enantioselective Sulfenofunctionalisation of Alkenes: Mechanistic, Crystallographic, and Computational Studies

    PubMed Central

    Denmark, Scott E.; Hartmann, Eduard; Kornfilt, David J. P.; Wang, Hao

    2015-01-01

    The stereocontrolled introduction of vicinal heteroatomic substituents into organic molecules is one of the most powerful ways of adding value and function. Whereas many methods exist for the introduction of oxygen- and nitrogen-containing substituents, the number stereocontrolled methods for the introduction of sulfur-containing substituents pales by comparison. Previous reports from these laboratories have described the sulfenofunctionalization of alkenes that construct vicinal carbon-sulfur and carbon-oxygen, carbon-nitrogen as well as carbon-carbon bonds with high levels of diastereospecificity and enantioselectivity. This process is enabled by the concept of Lewis base activation of Lewis acids that provides activation of Group 16 electrophiles. To provide a foundation for expansion of substrate scope and improved selectivities, we have undertaken a comprehensive study of the catalytically active species. Insights gleaned from kinetic, crystallographic and computational methods have led to the introduction of a new family of sulfenylating agents that provide significantly enhanced selectivities. PMID:25411883

  2. Enantioselective Synthesis of Pactamycin, a Complex Antitumor Antibiotic

    PubMed Central

    Malinowski, Justin T.; Sharpe, Robert J.; Johnson, Jeffrey S.

    2014-01-01

    Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally-intricate aminocyclopentitol antibiotic, displays potent anti-prolific properties across multiple phylogenetic domains, but is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Herein, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction/symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals fifteen steps and is immediately amenable for structural analog synthesis. PMID:23580525

  3. Highly enantioselective trapping of zwitterionic intermediates by imines

    NASA Astrophysics Data System (ADS)

    Qiu, Huang; Li, Ming; Jiang, Li-Qin; Lv, Feng-Ping; Zan, Li; Zhai, Chang-Wei; Doyle, Michael P.; Hu, Wen-Hao

    2012-09-01

    Reactions with the unstable and highly reactive zwitterionic intermediates generated in processes catalysed by transition metals are providing new opportunities for molecular constructions. Insertion reactions involve the collapse of zwitterionic intermediates, but trapping them would allow structural elaborations that are not currently available. To synthesize complex molecules in this manner, reactive electrophiles can be used to trap the zwitterionic intermediates. Here, we describe the use of imines, activated by chiral organocatalysts, and a highly efficient integrated rhodium and chiral Brønsted acid co-catalysed process to trap zwitterionic intermediates that have been proposed previously to undergo a formal C-H insertion reaction, allowing us to obtain polyfunctionalized indole and oxindole derivatives in a single step with excellent diastereoselectivity and enantioselectivity.

  4. Enantioselective synthesis of cyanohydrins catalysed by hydroxynitrile lyases - a review.

    PubMed

    Bracco, Paula; Busch, Hanna; von Langermann, Jan; Hanefeld, Ulf

    2016-07-01

    The first enantioselective synthesis was the selective addition of cyanide to benzaldehyde catalysed by a hydroxynitrile lyase (HNL). Since then these enzymes have been developed into a reliable tool in organic synthesis. HNLs to prepare either the (R)- or the (S)-enantiomer of the desired cyanohydrin are available and a wide variety of reaction conditions can be applied. As a result of this, numerous applications of these enzymes in organic synthesis have been described. Here the examples of the last decade are summarised, the enzyme catalysed step is discussed and the follow-up chemistry is shown. This proves HNLs to be part of main stream organic synthesis. Additionally the newest approaches via immobilisation and reaction engineering are introduced. PMID:27282284

  5. Photomechanical actuation of ligand geometry in enantioselective catalysis.

    PubMed

    Kean, Zachary S; Akbulatov, Sergey; Tian, Yancong; Widenhoefer, Ross A; Boulatov, Roman; Craig, Stephen L

    2014-12-22

    A catalyst that couples a photoswitch to the biaryl backbone of a chiral bis(phosphine) ligand, thus allowing photochemical manipulation of ligand geometry without perturbing the electronic structure is reported. The changes in catalyst activity and selectivity upon switching can be attributed to intramolecular mechanical forces, thus laying the foundation for a new class of catalysts whose selectivity can be varied smoothly and in situ over a useful range by controlling molecular stress experienced by the catalyst during turnover. Forces on the order of 100 pN are generated, thus leading to measurable changes in the enantioselectivities of asymmetric Heck arylations and Trost allylic alkylations. The differential coupling between applied force and competing stereochemical pathways is quantified and found to be more efficient for the Heck arylations. PMID:25359436

  6. Enantioselectivity in toxicity and degradation of dichlorprop-methyl in algal cultures.

    PubMed

    Li, Hong; Yuan, Yuli; Shen, Chensi; Wen, Yuezhong; Liu, Huijun

    2008-05-01

    Enantioselectivity in the toxicity and degradation of the herbicide dichlorprop-methyl (2,4-DCPPM) in algal cultures was studied. Enantioselectivity was clearly observed in the toxicity of racemic 2,4-DCPPM and its two enantiomers. R-2,4-DCPPM showed low toxicity to Chlorella pyrenoidosa and Chlorella vulgaris, but higher toxicity to Scenedesmus obliquus. The observed toxicity was ranked: R-2,4-DCPPM>S-2,4-DCPPM>Rac-2,4-DCPPM; the toxicity of R-2,4-DCPPM was about 8-fold higher than that of Rac-2,4-DCPPM. Additionally, 2,4-DCPPM was quickly degraded, in the initial 12 h, and different algae cultures had different enantioselectivity for the 2,4-DCPPM enantiomers. There was no significant enantioselectivity for 2,4-DCPPM in Chlorella vulgaris in the initial 7 h. However, racemic 2,4-DCPPM was degraded by Scenedesmus obliquus quickly, in the initial 4 h, much quicker, in fact, than the S- or R-enantiomers (racemate>R->S-), indicating that the herbicide 2,4-DCPPM was absorbed enantioselectively by Scenedesmus obliquus. The rapid formation of 2,4-DCPP suggested that 2,4-DCPPM adsorbed by algal cells was catalytically hydrolyzed to the free acid, a toxic metabolite. The production rates of 2,4-DCPP were as follows: Scenedesmus obliquus>Chlorella pyrenoidosa>Chlorella vulgaris, consistent with the degradability of 2,4-DCPPM. Scenedesmus obliquus had quick, but different, degradative and uptake abilities for R-, S-, and Rac-2,4-DCPPM. The R- and S- enantiomers were not hydrolyzed in the first 12 h, while both enantiomers were hydrolyzed slowly after that. These results indicate that some physical and chemical properties of compounds are of importance in determining their enantioselective toxicity and degradation. The ester and its metabolite likely played an important role in enantioselective toxicity to the three algae. PMID:18437615

  7. Evidence for the effect of sorption enantioselectivity on the availability of chiral pesticide enantiomers in soil.

    PubMed

    Gámiz, Beatriz; Facenda, Gracia; Celis, Rafael

    2016-06-01

    Although enantioselective sorption to soil particles has been proposed as a mechanism that can potentially influence the availability of individual chiral pesticide enantiomers in the environment, environmental fate studies generally overlook this possibility and assume that only biotic processes can be enantioselective, whereas abiotic processes, such as sorption, are non-enantioselective. In this work, we present direct evidence for the effect of the enantioselective sorption of a chiral pesticide in a natural soil on the availability of the single pesticide enantiomers for transport. Batch sorption experiments, with direct determination of the sorbed amounts, combined with column leaching tests confirmed previous observations that from non-racemic aqueous solutions the sorption of the chiral fungicide metalaxyl on the soil appeared to be enantioselective, and further demonstrated that the enantiomer that was sorbed to a greater extent (R-metalaxyl, Kd = 1.73 L/kg) exhibited retarded leaching compared to its optical isomer (S-metalaxyl, Kd = 1.15 L/kg). Interconversion and degradation of the pesticide enantiomers, which are potential experimental artifacts that can lead to erroneous estimates of sorption and its enantioselectivity, were discarded as possible causes of the observed enantioselective behavior. The results presented here may have very important implications for a correct assessment of the environmental fate of chiral pesticides that are incorporated into the environment as non-racemic mixtures, and also of aged chiral pesticide residues that have been transformed from racemic to non-racemic by biologically-mediated processes. PMID:27060281

  8. Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls.

    PubMed

    Liang, Tao; Zhang, Wandi; Chen, Te-Yu; Nguyen, Khoa D; Krische, Michael J

    2015-10-14

    The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo-, and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k, and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k, and 6m, respectively. Primary alcohols 2a, 2l, and 2p were converted to the siloxy-crotylation products 3a, 3l, and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l, and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes. PMID:26418572

  9. Catalytic asymmetric reductive coupling of alkynes and aldehydes: enantioselective synthesis of allylic alcohols and alpha-hydroxy ketones.

    PubMed

    Miller, Karen M; Huang, Wei-Sheng; Jamison, Timothy F

    2003-03-26

    A highly enantioselective method for catalytic reductive coupling of alkynes and aldehydes is described. Allylic alcohols are afforded with complete E/Z selectivity, generally >95:5 regioselectivity, and in up to 96% ee. In conjunction with ozonolysis, this process is complementary to existing methods of enantioselective alpha-hydroxy ketone synthesis. PMID:12643701

  10. Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Chiral O,N,O-tridentate Phenol Ligands Derived From Camphor.

    PubMed

    Lee, Dong-Sheng; Chang, Shu-Ming; Ho, Chun-Ying; Lu, Ta-Jung

    2016-01-01

    Chiral O,N,O-tridentate phenol ligands bearing a camphor backbone were found to be effective chiral catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes, resulting in high enantioselectivities (80-95% ee) at room temperature. PMID:26487505

  11. Asymmetric azidation-cycloaddition with open-chain peptide-based catalysts. A sequential enantioselective route to triazoles.

    PubMed

    Guerin, David J; Miller, Scott J

    2002-03-13

    A family of beta-substituted histidine-containing peptides has been synthesized to probe the effect of noncovalent conformational rigidification on catalyst enantioselectivity. Unambiguous enhancement of enantioselectivity in the conjugate addition of azide to alpha,beta-unsaturated carboxylate derivatives has been achieved, enabling application to a sequential asymmetric azidation/cycloaddition for the synthesis of optically enriched triazoles and triazolines. PMID:11878965

  12. Direct Enantioselective Vinylogous Mannich Reaction of Ketimines with γ-Butenolide by Using Cinchona Alkaloid Amide/Zinc(II) Catalysts.

    PubMed

    Nakamura, Shuichi; Yamaji, Ryota; Hayashi, Masashi

    2015-06-26

    A direct enantioselective vinylogous Mannich reaction of ketimines with γ-butenolide has been developed. Good yields and enantioselectivities were observed for the reaction of various ketimines by using a cinchona alkaloid amide/Zn(OTf)2 catalyst and Et3N. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. PMID:25944609

  13. Rhodium-Catalyzed Enantioselective Intermolecular Hydroalkoxylation of Allenes and Alkynes with Alcohols: Synthesis of Branched Allylic Ethers.

    PubMed

    Liu, Zi; Breit, Bernhard

    2016-07-11

    Regio- and enantioselective additions of alcohols to either terminal allenes or internal alkynes provides access to allylic ethers by using a Rh(I) /diphenyl phosphate catalytic system. This method provides an atom-economic way to obtain chiral aliphatic and aryl allylic ethers in moderate to good yield with good to excellent enantioselectivities. PMID:27244349

  14. Enantioselective [4 + 2]-Annulation of Oxadienes and Allenones Catalyzed by an Amino Acid Derived Phosphine: Synthesis of Functionalized Dihydropyrans.

    PubMed

    Ni, Huanzhen; Yao, Weijun; Waheed, Abdul; Ullah, Nisar; Lu, Yixin

    2016-05-01

    An enantioselective [4 + 2]-annulation process between cyano-activated oxadienes and allenones is developed. An l-valine-derived phosphine was efficient in catalyzing the reaction, and a wide range of highly functionalized dihydropyrans were prepared in high yields and with excellent enantioselectivities. PMID:27091405

  15. Enantioselective Transesterification Catalysis by Nanosized Serine Protease Subtilisin Carlsberg Particles in Tetrahydrofuran

    PubMed Central

    Castillo, Betzaida; Delgado, Yamixa; Barletta, Gabriel; Griebenow, Kai

    2010-01-01

    Enzyme catalysis in organic solvents is a powerful tool for stereo-selective synthesis but the enantioselectivity is still hard to predict. To overcome this obstacle, we employed a nanoparticulate formulation of subtilisin Carlsberg (SC) and designed a series of 14 structurally related racemic alcohols. They were employed in the model transesterification reaction with vinyl butyrate and the enantioselectivities were determined. In general, short alcohol side chains led to low enantioselectivties, while larger and bulky side chains caused better discrimination of the enantiomers by the enzyme. With several bulky substrates high enantioselectivities with E>100 were obtained. Computational modeling highlighted that key to high enantioselectivity is the discrimination of the R and S substrates by the sole hydrophobic binding pocket based on their size and bulkiness. While bulky S enantiomer side chains could be accommodated within the binding pocket, bulky R enantiomer side chains could not. However, when also the S enantiomer side chain becomes too large and does not fit into the binding pocket anymore, enantioselectivity accordingly drops. PMID:20661313

  16. Enantioselective degradation of chiral insecticide dinotefuran in greenhouse cucumber and soil.

    PubMed

    Chen, Xiu; Dong, Fengshou; Xu, Jun; Liu, Xingang; Wang, Yunhao; Zheng, Yongquan

    2015-02-01

    The enantioselective degradation behavior of the chiral insecticide dinotefuran in cucumber and soil was investigated under greenhouse conditions based on the method established with a normal-phase high-performance chromatography (HPLC) on a ChromegaChiral CCA column (250 × 4.6 mm, 5 µm, ES Industries). The linearity range, matrix effect, precision, and accuracy of the method were evaluated and the method was then successfully applied for the enantioselective analysis of dinotefuran in cucumber and soil. Significant enantioselectivity of degradation was observed in soil according to the results. The (+)-dinotefuran was more persistent in soil with half-life of 21.7 d, which is much longer than that of (-)-dinotefuran (16.5 d). In cucumber, the (-)-dinotefuran also tended to be preferentially degraded both in foliar and douche treatment. However, the statistical analysis indicated the enantioselectivity of degradation in cucumber was not significant. The research provides the first report concerning the enantioselective degradation of dinotefuran enantiomers and the results can be used for understanding the insect-controlling effect and food safety evaluation. PMID:25378099

  17. Characterization of Diastereo- and Enantioselectivity in Degradation of Synthetic Pyrethroids in Soils.

    PubMed

    Li, Shaotong; Li, Zhaoyang; Li, Qiaoling; Zhao, Jiahe; Li, Sen

    2016-01-01

    Permethrin (PM), cypermethrin (CP), and cyfluthrin (CF) are three important synthetic pyrethroids, which contain two, four, and four enantiomeric pairs (diastereomers) and thus have four, eight, and eight stereoisomers, respectively. In this study, the stereo- and enantioselective degradation of PM, CP, and CF in a Shijiazhuang alkaline yellow soil and a Wuhan acidic red soil were studied in detail by a combination of achiral and chiral high-performance liquid chromatography (HPLC). The results showed that PM, CP, and CF degraded faster in Shijiazhuang soil than in Wuhan soil, and the dissipation rate followed an order of PM > CF > CP in both soils. The three pyrethroids exhibited similar diastereomer selectivity, while CP and CF showed higher enantioselectivity than PM. Moreover, the trans-diastereomers degraded faster, and showed higher enantioselectivity than the corresponding cis-diastereomers. For PM, the enantiomer 1S-trans-PM degraded most rapidly in both soils. As for CP and CF, the highest enantioselectivity was observed for diastereomer trans-3, and the insecticidally active enantiomer 1R-trans-αS degraded fastest among the 8 CP or CF stereoisomers in both soils. In addition, the Wuhan acidic soil displayed higher diastereomer and enantiomer selectivity than the Shijiazhuang alkaline soil for the three pyrethroids. Further incubation of CF in an alkaline-treated Wuhan soil showed that the dissipation rate greatly increased and the diastereo- and enantioselectivity significantly decreased after the alkaline treatment process. PMID:26497288

  18. Synthesis of aliphatic sulfur pentafluorides by oxidation of SF₅-containing anisole, phenols, and anilines.

    PubMed

    Vida, Norbert; Pastýříková, Tereza; Klepetářová, Blanka; Beier, Petr

    2014-09-19

    4-(Pentafluorosulfanyl)catechol, 2-amino-4-(pentafluorosulfanyl)phenol, and 2-amino-5-(pentafluorosulfanyl)phenol undergo oxidation by lead tetraacetate at ambient temperature leading to dearomatization and the formation of SF5-substituted nitriles and esters of cis,cis-hexa-2,4-dienedioic (muconic) acid in good yields. 4-(Pentafluorosulfanyl)phenol and 4-(pentafluorosulfanyl)anisole are oxidized by 30% aqueous hydrogen peroxide in concentrated sulfuric acid to provide 2-(5-oxo-3-(pentafluorosulfanyl)-2,5-dihydrofuran-2-yl)acetic acid [3-(pentafluorosulfanyl)muconolactone] and small amounts of side products--SF5-containing maleic and succinic acids. The methods presented are the first examples of the practical synthesis of aliphatic SF5-containing compounds from readily available aromatic ones. PMID:25137015

  19. Enantioselective synthesis of helical polydiacetylene by application of linearly polarized light and magnetic field

    NASA Astrophysics Data System (ADS)

    Xu, Yangyang; Yang, Guang; Xia, Hongyan; Zou, Gang; Zhang, Qijin; Gao, Jiangang

    2014-09-01

    Magnetic optical activity, which can occur in all media and is induced by longitudinal magnetic field, causes the difference in absorption coefficients of left and right circularly polarized light and has the potential for magnetically induced enantioselectivity in chemical reactions. Compared with the well-established technique with circularly polarized light, there are few reports on the production of helical conjugated polymers in a photochemical reaction based on above magnetochiral anisotropy mechanism. Herein, we demonstrate experimentally that the enantioselective polymerization of diacetylene derivative can be achieved in the liquid crystal phase by application of linearly polarized light under a parallel or antiparallel magnetic field. The screw direction of predominant helical polydiacetylene chain can be rigorously controlled with the relative orientation of linearly polarized light and the magnetic field. Moreover, the prepared helical polydiacetylene assemblies can serve as a direct visual probe for the enantioselective recognition of D- or L-lysine.

  20. Enantioselective bioaccumulation and degradation of sediment-associated metalaxyl enantiomers in Tubifex tubifex.

    PubMed

    Di, Shanshan; Liu, Tiantian; Diao, Jinling; Zhou, Zhiqiang

    2013-05-29

    Knowledge about the enantioselective bioavailability of chiral pesticides in aquatic organisms facilitates more accurate interpretation of their environmental behaviors. In this study, the enantioselective bioaccumulation of metalaxyl enantiomers in Tubifex tubifex was detected in two uptake pathways. For the spike water treatment, a 16 day exposure experiment was employed and the enantiomer fractions (EFs) in tubifex tissue were maintained approximately at 0.47 during the experiment. For the spike sediment treatment, a 14 day bioaccumulation period indicated the concentrations of (-)-(R)-metalaxyl were higher than those of (+)-(S)-metalaxyl. Therefore, the bioaccumulation of metalaxyl in worms was enantioselective for these treatments. With the presence of tubifex, higher concentrations of metalaxyl in overlying water and lower concentrations in sediment were detected than in worm-free treatments. This means that tubifex has positive functions in metalaxyl's diffusion from the sediment to overlying water and in the degradation of the sediment-associated metalaxyl. PMID:23635317

  1. A Preparation of (−)-Nutlin-3 Using Enantioselective Organocatalysis at Decagram Scale

    PubMed Central

    Davis, Tyler A.; Vilgelm, Anna E.; Richmond, Ann; Johnston, Jeffrey N.

    2013-01-01

    Chiral nonracemic cis-4,5-bis(aryl) imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (−)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (−20 °C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (−)-Nutlin-3 in a 17 gram batch, and elimination of all but three chromatographic purifications. PMID:24127627

  2. Enantioselective Rhodium-Catalyzed Cycloisomerization of (E)-1,6-Enynes.

    PubMed

    Deng, Xu; Ni, Shao-Fei; Han, Zheng-Yu; Guan, Yu-Qing; Lv, Hui; Dang, Li; Zhang, Xu-Mu

    2016-05-17

    An enantioselective rhodium(I)-catalyzed cycloisomerization reaction of challenging (E)-1,6-enynes is reported. This novel process enables (E)-1,6-enynes with a wide range of functionalities, including nitrogen-, oxygen-, and carbon-tethered (E)-1,6-enynes, to undergo cycloisomerization with excellent enantioselectivity, in a high-yielding and operationally simple manner. Moreover, this Rh(I) -diphosphane catalytic system also exhibited superior reactivity and enantioselectivity for (Z)-1,6-enynes. A rationale for the striking reactivity difference between (E)- and (Z)-1,6-enynes using Rh(I) -BINAP and Rh(I) -TangPhos is outlined using DFT studies to provide the necessary insight for the design of new catalyst systems and the application to synthesis. PMID:27061132

  3. Enantioselective separation of chiral arylcarboxylic acids on an immobilized human serum albumin chiral stationary phase.

    PubMed

    Andrisano, V; Booth, T D; Cavrini, V; Wainer, I W

    1997-01-01

    A series of 12 chiral arylcarboxylic acids were chromatographed on an immobilized human serum albumin chiral stationary phase (HSA-CSP). The effects of solute structure on chromatographic retentions and enantioselective separations were examined by linear regression analysis and the construction of quantitative structure-enantioselective retention relationships. Competitive displacement studies were also conducted using R-ibuprofen as the displacing agent. The results indicate that the enantioselective retention of the solutes takes place at the indole-benzodiazepine site (site II) on the HSA molecule and that chiral recognition is affected by the hydrophobicity and steric volume of the solutes. The displacement studies also identified a cooperative allosteric interaction induced by the binding of R-ibuprofen to site II. PMID:9134695

  4. Evaluation of the enantioselective binding of imazalil to human serum albumin by capillary electrophoresis.

    PubMed

    Asensi-Bernardi, Lucía; Martín-Biosca, Yolanda; Escuder-Gilabert, Laura; Sagrado, Salvador; Medina-Hernández, María José

    2015-11-01

    In this work, a methodology for the evaluation of enantioselective binding of imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the separation of free and bound to HSA fractions is developed. This methodology comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the capillary electrophoresis system and the subsequent direct injection and chiral separation of IMA employing highly sulfated β-cyclodextrin as chiral selector and the complete filling technique. Two mathematical approaches were used to estimate apparent affinity constants (K1), protein binding and enantioselectivity (ES) for both enantiomers of IMA. Moderate enantioselective binding of IMA enantiomers to HSA (ES = 2.0) was shown by the 1:1 stoichiometry and log K1 values of 3.4 ± 0.4 and 3.1 ± 0.3 for the first and second eluted enantiomers, respectively. PMID:25857268

  5. Development of Chiral Bis-hydrazone Ligands for the Enantioselective Cross-Coupling Reactions of Aryldimethylsilanolates

    PubMed Central

    2015-01-01

    A palladium-catalyzed, enantioselective, aryl–aryl cross-coupling reaction using 1-naphthyldimethylsilanolates and chiral bis-hydrazone ligands has been developed. A family of glyoxal bis-hydrazone ligands containing various 2,5-diarylpyrrolidine groups was prepared to evaluate the influence of ligand structure on the rate and enantioselectivity of the cross-coupling. New synthetic routes to the 1-amino-2,5-diarylpyrrolidines were developed to enable the structure/reactivity–selectivity studies. Role reversal experiments of aryldimethylsilanolates and aryl bromides result in biaryl products with the same configuration and similar enantioselectivities implying that reductive elimination is the stereodetermining step. The origin of stereoselectivity is rationalized through computational modeling of diarylpalldium(II) complex which occurs through a conrotatory motion for the two aryl groups undergoing C–C bond formation. PMID:25494058

  6. Enantioselective Catalysis of the Aza-Cope Rearrangement by a Chiral Supramolecular Assembly

    SciTech Connect

    Brown, Casey J.; Bergman, Robert G.; Raymond, Kenneth N.

    2009-07-29

    The chiral supramolecular catalyst Ga{sub 4}L{sub 6} [L = 1,5-bis(2,3-dihydroxybenzoylamino)naphthalene] is a molecular tetrahedron that catalyzes the 3-aza-Cope rearrangement of allyl enammonium cations. This catalysis is accomplished by preorganizing the substrate in a reactive conformation within the host. This work demonstrates that through the use of enantiopure assembly, its chiral cavity is capable of catalyzing the 3-aza-Cope rearrangement enantioselectively, with yields of 21-74% and enantiomeric excesses from 6 to 64% at 50 C. At lower temperatures, the enantioselectivity improved, reaching 78% ee at 5 C. This is the highest enantioselectivity to date induced by the chiral cavity of a supramolecular assembly.

  7. Catalytic enantioselective addition of organoboron reagents to fluoroketones controlled by electrostatic interactions

    NASA Astrophysics Data System (ADS)

    Lee, Kyunga; Silverio, Daniel L.; Torker, Sebastian; Robbins, Daniel W.; Haeffner, Fredrik; van der Mei, Farid W.; Hoveyda, Amir H.

    2016-08-01

    Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium–organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities.

  8. Catalytic enantioselective addition of organoboron reagents to fluoroketones controlled by electrostatic interactions.

    PubMed

    Lee, KyungA; Silverio, Daniel L; Torker, Sebastian; Robbins, Daniel W; Haeffner, Fredrik; van der Mei, Farid W; Hoveyda, Amir H

    2016-08-01

    Organofluorine compounds are central to modern chemistry, and broadly applicable transformations that generate them efficiently and enantioselectively are in much demand. Here we introduce efficient catalytic methods for the addition of allyl and allenyl organoboron reagents to fluorine-substituted ketones. These reactions are facilitated by readily and inexpensively available catalysts and deliver versatile and otherwise difficult-to-access tertiary homoallylic alcohols in up to 98% yield and >99:1 enantiomeric ratio. Utility is highlighted by a concise enantioselective approach to the synthesis of the antiparasitic drug fluralaner (Bravecto, presently sold as the racemate). Different forms of ammonium-organofluorine interactions play a key role in the control of enantioselectivity. The greater understanding of various non-bonding interactions afforded by these studies should facilitate the future development of transformations that involve fluoroorganic entities. PMID:27442282

  9. Arthrobacter sp. lipase immobilization for improvement in stability and enantioselectivity.

    PubMed

    Chaubey, Asha; Parshad, Rajinder; Koul, Surrinder; Taneja, Subhash C; Qazi, Ghulam N

    2006-12-01

    Arthrobacter sp. lipase (ABL, MTCC no. 5125) is being recognized as an efficient enzyme for the resolution of drugs and their intermediates. The immobilization of ABL on various matrices for its enantioselectivity, stability, and reusability has been studied. Immobilization by covalent bonding on sepharose and silica afforded a maximum of 380 and 40 IU/g activity, respectively, whereas sol-gel entrapment provided a maximum of 150 IU/g activity in dry powder. The immobilized enzyme displayed excellent stability in the pH range of 4-10 and even at higher temperature, i.e., 50-60 degrees C, compared to free enzyme, which is unstable under extreme conditions. The resolution of racemic auxiliaries like 1-phenyl ethanol and an intermediate of antidepressant drug fluoxetine, i.e., ethyl 3-hydroxy-3-phenylpropanoate alkyl acylates, provided exclusively R-(+) products ( approximately 99% ee, E=646 and 473), compared to cell free extract/whole cells which gave a product with approximately 96% ee (E=106 and 150). The repeated use (ten times) of covalently immobilized and entrapped ABL resulted in no loss in activity, thus demonstrating its prospects for commercial applications. PMID:16896604

  10. Enantioselective Recognition in Solution: The Case of Countercurrent Chromatography

    NASA Astrophysics Data System (ADS)

    Rubio, Núria; Minguillón, Cristina

    Countercurrent chromatography (CCC) is a preparative separation technique that works with a liquid stationary phase. Biphasic liquid systems are needed to perform a separation. Since a chiral selector is required to perform enantiomer separations, special requirements are imposed in CCC. The chiral selector (CS) must be located in the stationary phase since partitioning with the mobile phase would cause losses of the valuable chiral selector in the mobile phase. Sulfated cyclodextrins and proteins were used as polar CS located in the polar stationary phase (reversed phase mode). Apolar CSs such as N-dodecyl-L-proline 3,5-dimethylanilide or Whelk-O selectors, quinine and quinidine derivatives, cellulose or amylose apolar derivatives were used located in the apolar stationary phase (normal phase mode). The special CCC displacement method called pH-zone refining was found useful in the increase of the loading capacity for cellulose, quinine, quinidine, and proline-derived selectors. Dual and multidual mode uses of CCC could produce an increase in peak separation thereby broadening the applicability of moderately enantioselective CSs.

  11. Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols

    NASA Astrophysics Data System (ADS)

    Shi, Shi-Liang; Wong, Zackary L.; Buchwald, Stephen L.

    2016-04-01

    The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.

  12. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

    PubMed Central

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-01-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1–S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics. PMID:26916830

  13. Robert Boyle's chiral crystal chemistry: computational re-evaluation of enantioselective adsorption on quartz.

    PubMed

    Kahr, Bart; Chittenden, Brianne; Rohl, Andrew

    2006-02-01

    While searching for early examples of interactions of organic chromophores with minerals in the context of a systematic study of the process of dyeing crystals, we came across Robert Boyle's description of an experiment that may have been evidence of the enantioselective adsorption of a natural product, carminic acid (7-beta-D-glucopyranosyl-9,10-dihydro-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxo-2-anthracenecarboxylic acid), to the chiral surfaces of alpha-quartz, three centuries before such interactions became the subject of active chemical investigations. In order to determine whether Boyle did indeed observe enantioselective adsorption--albeit unbeknownst to him--we attempted to dye quartz with carminic acid according to his recipe. Quartz adsorbs carminic acid only because on heating it develops a network of microfissures that adsorb dye. This process depends on capillarity, not on specific non-covalent interactions; there is no evidence of enantioselectivity adsorption to heated crystals or enantioselective epitaxy to unheated crystals. These failures changed the focus of our inquiry: Why have almost all attempts to demonstrate the enantioselective adsorption of additives to quartz crystal surfaces been generally confounding and equivocal? In order to answer this question, we complement our experimental historical re-investigation with contemporary computational techniques for modeling crystal surface structure and the adsorption of additives. Minimizations of the energies associated with the adsorption of carminic acid to relaxed, hydrated d- and l-quartz {10(-)0} surfaces are analyzed in light of quartz's abysmal record as an enantioselective stationary phase. PMID:16385623

  14. Diastereodivergent and Enantioselective [4+2] Annulations of γ-Butenolides with Cyclic 1-Azadienes.

    PubMed

    Li, Chao; Jiang, Kun; Chen, Ying-Chun

    2015-01-01

    An asymmetric annulation reaction of γ-butenolides and cyclic 1-azadienes containing a 1,2-benzoisothiazole-1,1-dioxide motif has been studied, proceeding in a tandem Michael addition-aza-Michael addition sequence. Endo-type cycloadducts bearing fused tetracyclic skeletons were isolated in fair yields and with high enantioselectivity (up to >99% ee) under the catalysis of modified cinchona alkaloid (DHQD)2PHAL. Besides, exo-type diastereomers could be produced using β-isocupreidine (β-ICD) as the catalyst, though with moderate enantioselectivity. PMID:26225947

  15. Enantioselective Multicomponent Condensation Reactions of Phenols, Aldehydes, and Boronates Catalyzed by Chiral Biphenols.

    PubMed

    Barbato, Keith S; Luan, Yi; Ramella, Daniele; Panek, James S; Schaus, Scott E

    2015-12-01

    Chiral diols and biphenols catalyze the multicomponent condensation reaction of phenols, aldehydes, and alkenyl or aryl boronates. The condensation products are formed in good yields and enantioselectivities. The reaction proceeds via an initial Friedel-Crafts alkylation of the aldehyde and phenol to yield an ortho-quinone methide that undergoes an enantioselective boronate addition. A cyclization pathway was discovered while exploring the scope of the reaction that provides access to chiral 2,4-diaryl chroman products, the core of which is a structural motif found in natural products. PMID:26576776

  16. Development of an Enantioselective Route towards the Lycopodium Alkaloids: Total Synthesis of Lycopodine

    PubMed Central

    Yang, Hua; Carter, Rich G.

    2010-01-01

    Synthesis of a C15-desmethyl tricycle core of lycopodine has been accomplished. Key steps in the synthetic sequence include organocatalytic, intramolecular Michael addition of a keto sulfone and a tandem 1,3-sulfonyl shift / Mannich cyclization to construct the tricyclic core ring system. Synthetic work towards this natural product family led to the development of N-(p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide – an organocatalyst which facilitiates enantioselective, intramolecular Michael additions. A detailed mechanistic discussion is provided for both the intramolecular Michael addition and the sulfone rearrangement. Finally, the application of these discoveries to the enantioselective total synthesis of alkaloid lycopodine is described. PMID:20586477

  17. Mirror symmetry breaking with limited enantioselective autocatalysis and temperature gradients: a stability survey.

    PubMed

    Blanco, Celia; Ribó, Josep M; Crusats, Joaquim; El-Hachemi, Zoubir; Moyano, Albert; Hochberg, David

    2013-02-01

    We analyze limited enantioselective (LES) autocatalysis in a temperature gradient and with internal flow/recycling of hot and cold material. Microreversibility forbids broken mirror symmetry for LES in the presence of a temperature gradient alone. This symmetry can be broken however when the auto-catalysis and limited enantioselective catalysis are each localized within the regions of low and high temperature, respectively. This scheme has been recently proposed as a plausible model for spontaneous emergence of chirality in abyssal hydrothermal vents. Regions in chemical parameter space are mapped out in which the racemic state is unstable and bifurcates to chiral solutions. PMID:23238372

  18. Influence of biochar on the enantioselective behavior of the chiral fungicide metalaxyl in soil

    NASA Astrophysics Data System (ADS)

    Gámiz, Beatriz; Pignatello, Joseph J.; Hermosín, María Carmen; Cox, Lucía; Celis, Rafael

    2015-04-01

    Chiral pesticides comprise an emerging and important class of organic pollutants currently, accounting for more than a quarter of used pesticides. Consequently, the contamination problems caused by chiral pesticides are concern matter and factors affecting enantioselective processes of chiral pesticides in soil need to be understood. For example, certain soil management practices, such as the use of organic amendments, can affect the enantioselective behavior of chiral pesticides in soils. Recently, biochar (BC), i.e. organic matter subjected to pyrolysis, has been proposed as organic amendment due to beneficial properties such as its high stability against decay in soil environments and its apparent ability to influence the availability of nutrients. BC is considered to be more biologically inert as compared to otherforms of organic carbon. However, its side-effects on the enantioselectivity of processes affecting the fate of chiral pesticides is unknown. The aim of this study was to assess the effect of biochar (BC) on the enantioselectivity of sorption, degradation, and leaching of the chiral fungicide metalaxyl in an agricultural soil. Amending the soil with BC (2% w/w) resulted in 3 times higher sorption of metalaxyl enantiomers compared to unamended soil, but no enantioselectivity in the process was observed. Moreover, both enantiomers showed some resistance to be desorbed in BC-amended soil compared to unamended soil. Dissipation studies revealed that the degradation of metalaxylwas more enantioselective in the unamended soil than in BC-amended soil. In unamended soil, R-metalaxyl(biologically active) and S- metalaxyl had half-lives (t1/2) of 3 and 34 days, respectively. BC enhanced the persistence of both enantiomers in the soil, with R-metalaxyl being degraded faster (t1/2=43 days) than S-metalaxyl (t1/2= 100 days). The leaching of both S-and R-metalaxyl was almost suppressed after amending the soil with BC; less than 10% of the fungicide applied to soil

  19. Organocatalytic Enantioselective Aza-Friedel-Crafts Reaction of Cyclic Ketimines with Pyrroles using Imidazolinephosphoric Acid Catalysts.

    PubMed

    Nakamura, Shuichi; Matsuda, Nazumi; Ohara, Mutsuyo

    2016-07-01

    Organocatalytic enantioselective aza-Friedel-Crafts reactions of cyclic ketimines with pyrroles or indoles were catalyzed by imidazoline/phosphoric acid catalysts. The reaction was applied to various 3H-indol-3-ones to afford products in excellent yields and enantioselectivities. The chiral catalysts can be recovered by a single separation step using column chromatography and are reusable without further purification. Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction. PMID:27124556

  20. Enantioselective Rh(I)-Catalyzed Addition of Arylboronic Acids to Cyclic Ketimines.

    PubMed

    Kong, Jongrock; McLaughlin, Mark; Belyk, Kevin; Mondschein, Ryan

    2015-11-20

    A method for the enantioselective synthesis of chiral α-tertiary amines via Rh-catalyzed 1,2-addition of arylboronic acids to cyclic ketimines is described. The products are efficiently accessed in good yields and excellent enantioselectivities using a commercially available chiral ligand. The reaction scope includes vinyl, aryl, and heteroarylboronic acids with yields ranging from 40% to 99% and enantiomeric excesses from 88% to 99%. Conversion of an addition product into an α,α-diaryl-substituted amino acid is also demonstrated. PMID:26542775

  1. An ESI-MS Method to Determine Yield and Enantioselectivity in a Single Assay

    NASA Astrophysics Data System (ADS)

    Smith, Maureen E.; Knolls, Steven A.; Thompson, MyLe; Masterson, Douglas S.

    2015-03-01

    A mass spectrometry assay is presented here that allows for the simultaneous determination of yield and enantioselectivity in a single analysis. The assay makes use of molecules that are structurally similar to the analytes of interest as standards. The assay predicts the yields of the reactions reasonably well and with little error. For example, in the pig liver esterase catalyzed hydrolysis of one prochiral malonate, the yield predicted by the assay was 72%, while larger scale isolated reaction yields were within 5% of this value. This assay provides a fast method to determine yield and enantioselectivity in one analysis. The strengths and limitations of this method are discussed.

  2. Enantioselective CuH-catalyzed anti-Markovnikov hydroamination of 1,1-disubstituted alkenes.

    PubMed

    Zhu, Shaolin; Buchwald, Stephen L

    2014-11-12

    Enantioselective synthesis of β-chiral amines has been achieved via copper-catalyzed hydroamination of 1,1-disubstituted alkenes with hydroxylamine esters in the presence of a hydrosilane. This mild process affords a range of structurally diverse β-chiral amines, including β-deuterated amines, in excellent yields with high enantioselectivities. Furthermore, catalyst loading as low as 0.4 mol% could be employed to deliver product in undiminished yield and selectivity, demonstrating the practicality of this method for large-scale synthesis. PMID:25339089

  3. Highly Enantioselective, Intermolecular Hydroamination of Allenyl Esters Catalyzed by Bifunctional Phosphinothioureas

    PubMed Central

    2015-01-01

    Bifunctional phosphinothiourea catalysts have been developed successfully for the highly regio- and enantioselective γ-hydroamination of allenyl and propargyl esters with N-methoxy carbamate nucleophiles to yield α,β-unsaturated γ-amino acid ester products. In the case of propargyl ester substrates, the reaction proceeds through reversible phosphinothiourea-catalyzed isomerization to the corresponding allenyl ester. The high enantioselectivity of the process is attributed to a cooperative conjugate addition of a thiourea-bound carbamate anion to a vinyl phosphonium ion resulting from covalent activation of the allenyl ester substrate. PMID:25496451

  4. Diastereo- and enantioselective three-component coupling approach to highly substituted pyrrolidines.

    PubMed

    Chaulagain, Mani Raj; Felten, Albert E; Gilbert, Kevin; Aron, Zachary D

    2013-09-20

    The enantioselective synthesis of substituted pyrrolidines through a mild Lewis-acid catalyzed three-component coupling reaction between picolinaldehyde, amino acids, and activated olefins is reported. The reaction uses low catalyst loadings of commercially available chiral diamines and copper triflate proposed to self-assemble in conjunction with the chelating aldehydes, 4-substituted-2-picolinaldehydes or 4-methylthiazole-2-carboxaldehyde, to generate a catalyst complex. A model is provided to explain how this complex directs enantioselectivity. This work represents a significant advance in the ease, scope, and cost of producing highly substituted, enantioenriched pyrrolidines. PMID:23952564

  5. Enantioselective conjugate addition of alkylboranes catalyzed by a copper-N-heterocyclic carbene complex.

    PubMed

    Yoshida, Mika; Ohmiya, Hirohisa; Sawamura, Masaya

    2012-07-25

    The first catalytic enantioselective conjugate addition of alkylboron compounds has been achieved. Reactions between alkylboranes and imidazol-2-yl α,β-unsaturated ketones proceeded with high enantioselectivity under the influence of a Cu(I) catalyst system, prepared in situ from CuCl, a new chiral imidazolium salt as a precursor for the N-heterocyclic carbene ligand, and PhOK. Alkylboranes are widely obtained via alkene hydroboration. A variety of functional groups are tolerated in alkylboranes and α,β-unsaturated ketones. PMID:22746339

  6. Catalytic enantioselective aziridoarylation of aryl cinnamyl ethers toward synthesis of trans-3-amino-4-arylchromans.

    PubMed

    Hajra, Saumen; Sinha, Debarshi

    2011-09-16

    Catalytic enantioselective one-pot aziridoarylation reaction of aryl cinnamyl ethers has been demonstrated in detail. Combination of suitable copper catalyst and chiral bis-oxazoline ligand was found to be very efficient for asymmetric aziridination followed by intramolecular arylation (Friedel-Crafts) reaction to provide a general and direct method for the synthesis of trans-3-amino-4-arylchromans with high regio-, diastereo- (dr > 99:1), and enantioselectivity (up to 95% ee) with moderate yield. trans-3-Amino-4-arylchroman is an advanced intermediate for the synthesis of chromenoisoquinoline compounds such as doxanthrine, a potent and selective full agonist for the dopamine-D(1) receptor. PMID:21797274

  7. Enantioselective C-H carbene insertions with homogeneous and immobilized copper complexes.

    PubMed

    Fraile, José M; López-Ram-de-Viu, Pilar; Mayoral, José A; Roldán, Marta; Santafé-Valero, Jorge

    2011-09-01

    The efficiency of chiral bis(oxazoline)- and azabis(oxazoline)-copper complexes in the enantioselective carbene insertion into C-H bonds of cyclic ethers in homogeneous phase strongly depends on the structure of the substrate. The immobilization on laponite clay by electrostatic interactions not only allows the recovery and reuse of the heterogeneous catalysts, but in some cases also improves enantioselectivity and overall chemoselectivity, making possible reactions that do not take place or lead to low yields in solution, even with the commonly used Rh(2)[S-DOSP](4) catalyst. PMID:21750830

  8. Enantioselective synthesis of chiral heterocycles containing both chroman and pyrazolone derivatives catalysed by a chiral squaramide.

    PubMed

    Li, Jun-Hua; Du, Da-Ming

    2015-05-28

    An efficient chiral squaramide-catalysed enantioselective Michael addition of pyrazolin-5-ones to 3-nitro-2H-chromenes for the synthesis of chiral heterocyclic systems containing both chroman and pyrazolone derivatives has been developed. This reaction afforded the desired products in high to excellent yields (up to 98%) with high enantioselectivities (up to 96%) and excellent diastereoselectivities (up to 99 : 1) under very low catalyst loading (0.2 mol%). This catalytic asymmetric reaction provides an efficient route toward the synthesis of chiral heterocyclic systems containing both chroman and pyrazolone derivatives, which possess potential pharmaceutical activities. PMID:25882378

  9. Enantioselective stable isotope analysis (ESIA) of polar Herbicides

    NASA Astrophysics Data System (ADS)

    Maier, Michael; Qiu, Shiran; Elsner, Martin

    2013-04-01

    The complexity of aquatic systems makes it challenging to assess the environmental fate of chiral micropolutants. As an example, chiral herbicides are frequently detected in the environment (Buser and Muller, 1998); however, hydrological data is needed to determine their degradability from concentration measurements. Otherwise declining concentrations cannot unequivocally be attributed to degradation, but could also be caused by dilution effects. In contrast, isotope ratios or enantiomeric ratios are elegant alternatives that are independent of dilution and can even deliver insights into reaction mechanisms. To combine the advantages of both approaches we developed an enatioselective stable isotope analysis (ESIA) method to investigate the fate of the chiral herbicides 4-CPP ((RS)-2-(4-chlorophenoxy)-propionic acid), mecoprop (2-(4-Chloro-2-methylphenoxy)-propionic acid) and dichlorprop (2-(2,4-Dichlorophenoxy)-propionic acid). After testing the applicable concentration range of the method, enantioselective isotope fractionation was investigated by microbial degradation using dichlorprop as a model compound. The method uses enantioselective gas-chromatography (GC) to separate enantiomers. Subsequently samples are combusted online to CO2 and carbon isotope ratios are determined for each enantiomer by isotope-ratio-mass-spectrometry (IRMS). Because the analytes contain a polar carboxyl-group, samples were derivatised prior to GC-IRMS analysis with methanolic BF3 solution. Precise carbon isotope analysis (2σ ≤0.5‰) was achieved with a high sensitivity of ≥ 7 ng C that is needed on column for one analysis. Microbial degradation of the model compound dichlorprop was conducted with Delftia acidovorans MC1 and pronounced enantiomer fractionation, but no isotope fractionation was detected. The absence of isotope fractionation can be explained by two scenarios: either the degrading enzyme has no isotopic preference, or another step in the reaction without an isotopic

  10. Enantioselectivity in aquatic toxicity of synthetic pyrethroid insecticide fenvalerate.

    PubMed

    Ma, Yun; Chen, Linhua; Lu, Xianting; Chu, Huadong; Xu, Chao; Liu, Weiping

    2009-10-01

    Synthetic pyrethroids (SPs) are a family of chiral insecticides with a large number of stereoisomers. Fenvalerate (FV) is one of the most potent pyrethroid insecticides, controlling a wide range of insect pests in agricultural fields, public health situations and animal houses. FV contains two chiral centers. In this study, four stereoisomers of FV were absolutely separated by high-performance liquid chromatography with a commercial chiral column, CHIRALCEL OJ-H, using n-hexane containing 1,2-dichloroethane and ethanol as mobile phase. Toxicity assays of each isomer and racemate of FV were performed using Daphnia magna (D. magna), zebrafish (Danio rerio) and zebrafish embryo-larval. In the acute toxicity of D. magna, significant differences were observed: the 24h EC(50) of alphaS-2S-FV was 51 times more toxic than the alphaR-2R-FV, and the 48 h LC(50) results showed that the alphaS-2S-FV was 99 times more toxic than alphaR-2R-FV. In the toxicity assay of D. rerio, dramatic differences were also found: the LC(50) value of alphaS-2S-FV was 17, 22, 39 and 56 times more toxic than the alphaR-2R-FV at 24, 48, 72 and 96 h, respectively. The assays of 4-day-old zebrafish embryo-larval showed that the exposure to FV enantioselectively induced crooked body, yolk sac edema and pericardial edema and that the alphaS-2S-FV was 3.8 times stronger than the other isomers in 96-h mortality. The results indicate that the enantiomeric differences should be taken into consideration in assessing the ecological effects of SPs. PMID:19647873

  11. Enantioselective Phase-Transfer-Catalyzed Synthesis of Chiral N-Substituted 3,3-Dinitroazetidines by Aza-Michael Reaction.

    PubMed

    Lee, Hyo-Jun; Cho, Chang-Woo

    2015-11-20

    An efficient and highly enantioselective phase-transfer-catalyzed aza-Michael reaction of 3,3-dinitroazetidine, as N-centered nucleophile, to α,β-unsaturated ketones has been achieved using a quinidine-based phase-transfer catalyst (0.5-1 mol %), providing chiral N-substituted 3,3-dinitroazetidines in good yields (up to 99%) and excellent enantioselectivities (90-95% ee). This is the first example of the use of azetidines as N-centered nucleophiles in catalytic enantioselective aza-Michael reactions. PMID:26503134

  12. Catalytic Enantioselective Conjugate Alkynylation of β-Aryl-β-trifluoromethyl Enones Constructing Propargylic All-Carbon Quaternary Stereogenic Centers.

    PubMed

    Sanz-Marco, Amparo; Blay, Gonzalo; Vila, Carlos; Pedro, José R

    2016-08-01

    The enantioselective conjugate alkynylation of β-aryl-β-trifluoromethyl enones has been carried out using terminal alkynes and diethylzinc in the presence of 3,3'-bis(perfluorophenyl)BINOL as the chiral ligand to give the corresponding ketones bearing a trifluoromethylated propargylic quaternary stereocenter with fair to good enantioselectivities. Enones bearing a bulky 2-naphthyl attached to the carbonyl group provided the best enantioselectivities. The synthetic applicability of the resulting products has been demonstrated with their iodocyclization to form 4H-pyrans. PMID:27417872

  13. A homochiral metal-organic porous material for enantioselective separation and catalysis

    NASA Astrophysics Data System (ADS)

    Seo, Jung Soo; Whang, Dongmok; Lee, Hyoyoung; Jun, Sung Im; Oh, Jinho; Jeon, Young Jin; Kim, Kimoon

    2000-04-01

    Inorganic zeolites are used for many practical applications that exploit the microporosity intrinsic to their crystal structures. Organic analogues, which are assembled from modular organic building blocks linked through non-covalent interactions, are of interest for similar applications. These range from catalysis, separation and sensor technology to optoelectronics, with enantioselective separation and catalysis being especially important for the chemical and pharmaceutical industries. The modular construction of these analogues allows flexible and rational design, as both the architecture and chemical functionality of the micropores can, in principle, be precisely controlled. Porous organic solids with large voids and high framework stability have been produced, and investigations into the range of accessible pore functionalities have been initiated. For example, catalytically active organic zeolite analogues are known, as are chiral metal-organic open-framework materials. However, the latter are only available as racemic mixtures, or lack the degree of framework stability or void space that is required for practical applications. Here we report the synthesis of a homochiral metal-organic porous material that allows the enantioselective inclusion of metal complexes in its pores and catalyses a transesterification reaction in an enantioselective manner. Our synthesis strategy, which uses enantiopure metal-organic clusters as secondary building blocks, should be readily applicable to chemically modified cluster components and thus provide access to a wide range of porous organic materials suitable for enantioselective separation and catalysis.

  14. Enantioselective determination of triazole fungicide epoxiconazole bioaccumulation in tubifex based on HPLC-MS/MS.

    PubMed

    Liu, Chunxiao; Wang, Bo; Xu, Peng; Liu, Tiantian; Di, Shanshan; Diao, Jinling

    2014-01-15

    In this study, the enantioselective bioaccumulation of epoxiconazole enantiomers in tubifex (Oligochaeta, Tubificida) was investigated in two uptake pathways. A sensitive and rapid chiral method was developed for the determination of epoxiconazole enantiomers in tubifex and soil based on high-performance liquid chromatography coupled with triple-quadrupole mass spectrometry (HPLC-MS/MS). In the spiked-water or spiked-soil treatments, enantioselective bioaccumulation of epoxiconazole in tubifex was obersved. For spiked-water treatment, (-)-epoxiconazole accumulated in tubifex to a greater extent than (+)-epoxiconazole, leading to enrichments with a composition (-) > (+). However, for spiked-soil treatment, the enantioselectivity in tubifex was reversed with a preferential accumulation of (+)-epoxiconazole. Calculated accumulation factors (AFs) indicated that epoxiconazole in spiked-water treatment had higher bioaccumulation potential than that in spiked-soil treatment. The results from the spiked-soil treatment also revealed that the dissipation of epoxiconazole in soil was enantioselective, and tubifex has positive effects on epoxiconazole diffusion from soil to overlying water. PMID:24364671

  15. Enantioselective bioaccumulation of soil-associated fipronil enantiomers in Tubifex tubifex.

    PubMed

    Liu, Tiantian; Wang, Peng; Lu, Yuele; Zhou, Gaoxin; Diao, Jinling; Zhou, Zhiqiang

    2012-06-15

    Enantioselective behavior of chiral pesticides in the aquatic environment has been a subject of growing interest. In this study, the enantioselective bioaccumulation of fipronil enantiomers in Tubifex tubifex (Oligochaeta, Tubificida) was detected in both spike-water and spike-soil systems, respectively. For the spike-water treatment, a 9-day exposure experiment was employed and the enantiomer fraction in tubifex tissue was maintained approximately at 0.58 during the experiment. In addition, a 14-day bioaccumulation period was chosen for the spike-soil treatment and a more significant deviation of enantiomer fraction from 0.5 in tubifex tissue was detected, with concentrations of the R-form higher than that of the S-form. Therefore, the bioaccumulation of fipronil was enantioselective in tubifex tissue for the two treatments and the magnitude of enantioselectivity may be influenced by different exposure conditions. For the spike-soil treatment, the concentrations of fipronil in verlying water and soil were also determined. With the presence of tubifex worms, higher concentrations of fipronil in overlying water and lower concentrations in soil were detected than that in the absence of tubifex treatment during the whole 14-day exposure period. This means that tubifex has positive functions in fipronil's diffusion from soil to overlying water and in the degradation of the soil-associated fipronil. PMID:22502899

  16. A Green, Enantioselective Synthesis of Warfarin for the Undergraduate Organic Laboratory

    ERIC Educational Resources Information Center

    Wong, Terence C.; Sultana, Camille M.; Vosburg, David A.

    2010-01-01

    The enantioselective synthesis of drugs is of fundamental importance in the pharmaceutical industry. In this experiment, students synthesize either enantiomer of warfarin, a widely used anticoagulant, in a single step from inexpensive starting materials. Stereoselectivity is induced by a commercial organocatalyst, ("R","R")- or…

  17. Mechanistic basis for the enantioselectivity of the anaerobic hydroxylation of alkylaromatic compounds by ethylbenzene dehydrogenase.

    PubMed

    Szaleniec, Maciej; Dudzik, Agnieszka; Kozik, Bartłomiej; Borowski, Tomasz; Heider, Johann; Witko, Małgorzata

    2014-10-01

    The enantioselectivity of reactions catalyzed by ethylbenzene dehydrogenase, a molybdenum enzyme that catalyzes the oxygen-independent hydroxylation of many alkylaromatic and alkylheterocyclic compounds to secondary alcohols, was studied by chiral chromatography and theoretical modeling. Chromatographic analyses of 22 substrates revealed that this enzyme exhibits remarkably high reaction enantioselectivity toward (S)-secondary alcohols (18 substrates converted with >99% ee). Theoretical QM:MM modeling was used to elucidate the structure of the catalytically active form of the enzyme and to study the reaction mechanism and factors determining its high degree of enantioselectivity. This analysis showed that the enzyme imposes strong stereoselectivity on the reaction by discriminating the hydrogen atom abstracted from the substrate. Activation of the pro(S) hydrogen atom was calculated to be 500 times faster than of the pro(R) hydrogen atom. The actual hydroxylation step (i.e., hydroxyl group rebound reaction to a carbocation intermediate) does not appear to be enantioselective enough to explain the experimental data (the calculated rate ratios were in the range of only 2-50 for pro(S): pro(R)-oriented OH rebound). PMID:24950385

  18. Enantioselective addition of boronates to acyl imines catalyzed by chiral biphenols.

    PubMed

    Bishop, Joshua A; Lou, Sha; Schaus, Scott E

    2009-01-01

    On the big screen: A chiral biphenol catalyst screening protocol was developed for the rapid identification of enantioselective nucleophilic boronate reactions with acyl imines (see scheme). The approach successfully identified a unique catalyst for the reaction of aryl, vinyl, and alkynyl boronates. Mechanistic studies demonstrate boronate ligand exchange with the catalyst is necessary for activation towards nucleophilic addition. PMID:19431168

  19. Biphenol-based phosphoramidite ligands for the enantioselective copper-catalyzed conjugate addition of diethylzinc.

    PubMed

    Alexakis, Alexandre; Polet, Damien; Rosset, Stéphane; March, Sébastien

    2004-08-20

    Phosphoramidite ligands, based on ortho-substituted biphenols and a chiral amine, induce high enantioselectivities (ee's up to 99%) in the copper-catalyzed conjugate addition of dialkylzinc reagents to a variety of Michael acceptors. Particularly, the best reported ee's were obtained for acyclic nitroolefins. PMID:15307737

  20. Enantioselective Photocycloaddition of 3-Hydroxyflavones: Total Syntheses and Absolute Configuration Assignment of (+)-Ponapensin and (+)-Elliptifoline

    PubMed Central

    Lajkiewicz, Neil J.; Roche, Stéphane P.; Gerard, Baudouin

    2012-01-01

    We have previously reported development of biomimetic, asymmetric [3+2] photocycloadditions between 3-hydroxyflavones and cinnamate dipolarophiles to access (−)-rocaglamide and related natural products. Herein, we describe enantioselective syntheses of aglain cycloadducts leading to the first total syntheses and absolute configuration assignments of the aglain natural products (+)-ponapensin and (+)-elliptifoline. PMID:22804454

  1. Gold-Catalyzed Enantioselective Synthesis, Crystal Structure, and Photophysical/Chiroptical Properties of Aza[10]helicenes.

    PubMed

    Tanaka, Maya; Shibata, Yu; Nakamura, Kyosuke; Teraoka, Kota; Uekusa, Hidehiro; Nakazono, Kazuko; Takata, Toshikazu; Tanaka, Ken

    2016-07-01

    The enantioselective synthesis of an aza[10]helicene, possessing two pyridone units, has been achieved by the gold-catalyzed intramolecular quadruple hydroarylation of a tetrayne. This aza[10]helicene was successfully converted into a fully aromatic aza[10]helicene, possessing two pyridine units. Structure-photophysical and chiroptical properties relationship in a series of azahelicene isomers has also been disclosed. PMID:27128222

  2. Synthetic Study of Pactamycin: Enantioselective Construction of the Pactamycin Core with Five Contiguous Stereocenters.

    PubMed

    Yamaguchi, Mami; Hayashi, Minami; Hamada, Yasumasa; Nemoto, Tetsuhiro

    2016-05-20

    A synthetic study of pactamycin is described. Enantioselective construction of the aminocyclopentitol core of pactamycin bearing five contiguous stereocenters was achieved based on an organocatalytic asymmetric aziridination of 2-cyclopentene-1-one, a regio- and diastereoselective 1,3-dipolar cycloaddition, and a rhodium-catalyzed C-H amination reaction. PMID:27171747

  3. Enantioselective 1,1-Arylborylation of Alkenes: Merging Chiral Anion Phase Transfer with Pd Catalysis

    PubMed Central

    Miró, Javier; Toste, F. Dean

    2015-01-01

    A palladium-catalyzed three-component coupling of α-olefins, aryldiazonium salts, and bis-(pinacolato)diboron affords direct access to chiral benzylic boronic esters. This process is rendered highly enantioselective using an unprecedented example of cooperative chiral anion phase transfer and transition-metal catalysis. PMID:25723255

  4. Enantioselective Carbocycle Formation through Intramolecular Pd-Catalyzed Allyl–Aryl Cross-Coupling

    PubMed Central

    2015-01-01

    Aryl electrophiles containing tethered allylboronate units undergo efficient intramolecular coupling in the presence of a chiral palladium catalyst to give enantioenriched carbocyclic products. The reaction is found to be quite general, affording 5, 6, and 7-membered carbocyclic products as single regioisomers and with moderate enantioselectivities. Examination of differential coupling partners points to rapid allyl-equilibration as a key stereodefining feature. PMID:25105510

  5. Enantioselective Synthesis of (+)-Estrone Exploiting a Hydrogen Bond-Promoted Diels−Alder Reaction

    PubMed Central

    2010-01-01

    Starting from Dane’s diene and methylcyclopentenedione, (+)-estrone is synthesized along the Quinkert−Dane route in 24% total yield. The key step is an enantioselective Diels−Alder reaction promoted by an amidinium catalyst as efficiently as by a traditional Ti-TADDOLate Lewis acid. PMID:20302330

  6. Enantioselective total synthesis of (+)-Lingzhiol via tandem semipinacol rearrangement/Friedel-Crafts type cyclization.

    PubMed

    Chen, Dong; Xu, Wen-Dan; Liu, Hao-Miao; Li, Ming-Ming; Yan, Yong-Min; Li, Xiao-Nian; Li, Yan; Cheng, Yong-Xian; Qin, Hong-Bo

    2016-06-30

    Enantioselective total synthesis of (+)-Lingzhiol has been achieved. It is the first example of in tandem semipinacol rearrangement reactions, the migrated aryl group further reacting with the carbonyl oxonium electrophile to furnish a polycyclic skeleton. Our synthesis involves 13 steps and proceeds in 6% overall yield. PMID:27321202

  7. Enantioselective synthesis of tertiary α-chloro esters by non-covalent catalysis

    PubMed Central

    Liu, Richard Y.; Wasa, Masayuki; Jacobsen, Eric N.

    2015-01-01

    We report an enantioselective approach to tertiary α-chloro esters through the reaction of silyl ketene acetals and N-chlorosuccinimide. The reaction is promoted by a chiral squaramide catalyst, which is proposed to engage both reagents exclusively through non-covalent interactions. Application of the tertiary chloride products in stereospecific substitution reactions is demonstrated. PMID:26085694

  8. The Enantioselectivity of Odor Sensation: Some Examples for Undergraduate Chemistry Courses

    ERIC Educational Resources Information Center

    Kraft, Philip; Mannschreck, Albrecht

    2010-01-01

    This article discusses seven chiral odorants that demonstrate the enantioselectivity of odor sensation: carvone, Celery Ketone, camphor, Florhydral, 3-methyl-3-sulfanylhexan-1-ol, muscone, and methyl jasmonate. After a general introduction of the odorant-receptor interaction and the combinatorial code of olfaction, the olfactory properties of the…

  9. Enantioselective kinetics of α-hexachlorocyclohexane in earthworm (Eisenia fedtia) and forest soil.

    PubMed

    Zhou, Gaoxin; Liu, Donghui; Ma, Ruixue; Li, Jindong; Sun, Mingjing; Zhou, Zhiqiang; Wang, Peng

    2012-08-01

    The enantioselective bioaccumulation and elimination behaviors of α-hexachlorocyclohexane (α-HCH) enantiomers in earthworm and soil were investigated by chiral gas chromatography. Enantiomer fraction values were calculated as indicators of the enantioselectivity. The mature earthworms were exposed to 0.10 µg g(-1)(wwt) (0.14 µg g(-1)(dwt)) spiked soil continuously for the bioaccumulation, and the elimination was conducted after an enrichment period in the soil. The results showed that both the bioaccumulation and elimination processes followed monophasic kinetics, body residues of α-HCH in earthworm increased to high level at the fifth day, and enantioselectivity was found in the bioaccumulation process with the rate constant (k) of 0.80 d(-1) for (+)-α-HCH and 0.74 d(-1) for (-)-α-HCH. The half life (t(1/2)) of the enantiomers obtained in the elimination process was within one day. The bioaccumulation factors of steady state of α-HCH enantiomers were 2.82 for (+)-α-HCH and 2.75 for (-)-α-HCH. The enantiomer fractions of earthworm and soil obviously below 0.5 during uptake and elimination processes indicate significant enantioselectivity and preferential depuration of (+)-α-HCH in earthworm. However, earthworms do not have a great capacity for getting rid of α-HCH in polluted soil shown by a contradistinctive experiment. PMID:22674802

  10. Enantioselective acyl transfer catalysis by a combination of common catalytic motifs and electrostatic interactions

    PubMed Central

    Mandai, Hiroki; Fujii, Kazuki; Yasuhara, Hiroshi; Abe, Kenko; Mitsudo, Koichi; Korenaga, Toshinobu; Suga, Seiji

    2016-01-01

    Catalysts that can promote acyl transfer processes are important to enantioselective synthesis and their development has received significant attention in recent years. Despite noteworthy advances, discovery of small-molecule catalysts that are robust, efficient, recyclable and promote reactions with high enantioselectivity can be easily and cost-effectively prepared in significant quantities (that is, >10 g) has remained elusive. Here, we demonstrate that by attaching a binaphthyl moiety, appropriately modified to establish H-bonding interactions within the key intermediates in the catalytic cycle, and a 4-aminopyridyl unit, exceptionally efficient organic molecules can be prepared that facilitate enantioselective acyl transfer reactions. As little as 0.5 mol% of a member of the new catalyst class is sufficient to generate acyl-substituted all-carbon quaternary stereogenic centres in quantitative yield and in up to 98:2 enantiomeric ratio (er) in 5 h. Kinetic resolution or desymmetrization of 1,2-diol can be performed with high efficiency and enantioselectivity as well. PMID:27079273

  11. Asymmetric synthesis of L-carbidopa based on a highly enantioselective α-amination.

    PubMed

    Pericas, Àlex; Shafir, Alexandr; Vallribera, Adelina

    2013-04-01

    A stereoselective synthesis of L-carbidopa in seven steps and 50% overall yield from commercial compounds is described. The key step involves a highly enantioselective α-amination reaction of an acyclic β-ketoester with di-tert-butyl azodicarboxylate induced by europium and (R,R)-diphenyl-pybox. PMID:23477289

  12. Enantioselective Total Synthesis of (−)-Lansai B and (+)- Nocardioazines A and B **

    PubMed Central

    Wang, Haoxuan; Reisman, Sarah E.

    2014-01-01

    The concise total syntheses of the bis(pyrroloindolines) (−)-lansai B and (+)- nocardioazines A and B are reported. The key pyrroloindoline building blocks are rapidly prepared by enantioselective formal (3 + 2) cycloaddition reactions. The macrocycle of (+)-nocardioazine A is constructed by an unusual intramolecular diketopiperazine formation. PMID:24777757

  13. Enantioselective hydrogenation of pyruvic acid oxime to alanine on Pd/Alumina

    SciTech Connect

    Borszeky, K.; Mallat, T.; Aeschiman, R.

    1996-06-01

    The chemo- and enantioselective hydrogenation of pyruvic acid oxime have been studied on Pd/alumina, the latter in the presence of the 1,2-amino alcohol type alkaloids ephedrine, cinchonidine, and cinchonine. High yields of racemic alanine (90-98%) were obtained in the absence of alkaloids in polar solvents at 0-45{degrees}C and 10 bar. Enantioselection increased with higher temperature and alkalid: oxime molar ratio. A 1:1 ephedrine: oxime molar ratio afforded the best enantiomeric excess (26%). The presence of alkaloid resulted in a decrease of reaction rate by a factor of up to 140, compared to the racemic hydrogenation. Based on X-ray crystal structure analysis of the alkaloid-pyruvic acid oxime adduct, a mechanism is proposed for the steric course of the reaction. Extended interactions by multiple H bonds between the adsorbed alkaloid-oxime salt units on the Pd surface is assumed to be at the origin of the moderate enantioselectivity and the very low enantioselective hydrogenation rate. 28 refs., 5 figs., 3 tabs.

  14. Copper-catalyzed enantioselective C-H functionalization of indoles with an axially chiral bipyridine ligand.

    PubMed

    Gao, Xiang; Wu, Bo; Yan, Zhong; Zhou, Yong-Gui

    2016-09-21

    Using copper complexes with an axially chiral bipyridine ligand C4-ACBP as the catalyst, an enantioselective functionalization of indoles with diazo compounds was developed with up to 95% ee. This protocol paves the way for further applications of these ligands. PMID:27529404

  15. Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

    PubMed Central

    Liu, Jixin; Dasgupta, Srimoyee

    2015-01-01

    Summary The development of enantioselective, copper-catalyzed alkynylations of cyclic iminium and oxocarbenium ions is reviewed. The use of chiral copper-based catalysts has enabled high yields and enantioselectivites in the formation of nitrogen- and oxygen-containing heterocycles with α-stereogenic centers. This review highlights both the accomplishments and the future work needed in this important area. PMID:26877791

  16. Organic co-solvents affect activity, stability and enantioselectivity of haloalkane dehalogenases.

    PubMed

    Stepankova, Veronika; Damborsky, Jiri; Chaloupkova, Radka

    2013-06-01

    Haloalkane dehalogenases are microbial enzymes with a wide range of biotechnological applications, including biocatalysis. The use of organic co-solvents to solubilize their hydrophobic substrates is often necessary. In order to choose the most compatible co-solvent, the effects of 14 co-solvents on activity, stability and enantioselectivity of three model enzymes, DbjA, DhaA, and LinB, were evaluated. All co-solvents caused at high concentration loss of activity and conformational changes. The highest inactivation was induced by tetrahydrofuran, while more hydrophilic co-solvents, such as ethylene glycol and dimethyl sulfoxide, were better tolerated. The effects of co-solvents at low concentration were different for each enzyme-solvent pair. An increase in DbjA activity was induced by the majority of organic co-solvents tested, while activities of DhaA and LinB decreased at comparable concentrations of the same co-solvent. Moreover, a high increase of DbjA enantioselectivity was observed. Ethylene glycol and 1,4-dioxane were shown to have the most positive impact on the enantioselectivity. The favorable influence of these co-solvents on both activity and enantioselectivity makes DbjA suitable for biocatalytic applications. This study represents the first investigation of the effects of organic co-solvents on the biocatalytic performance of haloalkane dehalogenases and will pave the way for their broader use in industrial processes. PMID:23420811

  17. Computationally efficient and accurate enantioselectivity modeling by clusters of molecular dynamics simulations.

    PubMed

    Wijma, Hein J; Marrink, Siewert J; Janssen, Dick B

    2014-07-28

    Computational approaches could decrease the need for the laborious high-throughput experimental screening that is often required to improve enzymes by mutagenesis. Here, we report that using multiple short molecular dynamics (MD) simulations makes it possible to accurately model enantioselectivity for large numbers of enzyme-substrate combinations at low computational costs. We chose four different haloalkane dehalogenases as model systems because of the availability of a large set of experimental data on the enantioselective conversion of 45 different substrates. To model the enantioselectivity, we quantified the frequency of occurrence of catalytically productive conformations (near attack conformations) for pairs of enantiomers during MD simulations. We found that the angle of nucleophilic attack that leads to carbon-halogen bond cleavage was a critical variable that limited the occurrence of productive conformations; enantiomers for which this angle reached values close to 180° were preferentially converted. A cluster of 20-40 very short (10 ps) MD simulations allowed adequate conformational sampling and resulted in much better agreement to experimental enantioselectivities than single long MD simulations (22 ns), while the computational costs were 50-100 fold lower. With single long MD simulations, the dynamics of enzyme-substrate complexes remained confined to a conformational subspace that rarely changed significantly, whereas with multiple short MD simulations a larger diversity of conformations of enzyme-substrate complexes was observed. PMID:24916632

  18. Conazole Fungicides as Chiral Environmental Contaminants: Enantiomer Analysis and Enantioselectivity in Soil Slurries

    EPA Science Inventory

    Conazoles are triazole compounds, many of which are in wide use as agricultural and medicinal fungicides. Opportunities exist for them to contaminate the environment and, since they are all chiral molecules, they are apt to be degraded enantioselectively by indigenous microbes. T...

  19. AN IN SILICO INVESTIGATION OF THE ENANTIOSELECTIVE METABOLISM RATES OF TRIAZOLE FUGICIDES

    EPA Science Inventory

    The objective of this work is to use in silico methods such as ab initio quantum and classical force-field methods to explore and develop an understanding for the enantioselective metabolism rates experimentally observed in the triazole fungicide bromuconazole. This directed stud...

  20. Catalytic enantioselective diboration, disilation and silaboration: new opportunities for asymmetric synthesis.

    PubMed

    Burks, Heather E; Morken, James P

    2007-12-01

    This article summarizes recent developments in the area of catalytic enantioselective reactions of unsaturated organic substrates with diboron, silylboron, and disilane reagents. These reactions provide new routes to the functionalization of prochiral substrates and therefore offer new strategies in asymmetric organic synthesis. PMID:18004420

  1. Organocatalytic enantioselective γ-aminoalkylation of unsaturated ester: access to pipecolic acid derivatives.

    PubMed

    Xu, Jianfeng; Jin, Zhichao; Chi, Yonggui Robin

    2013-10-01

    The direct γ-carbon functionalization of α,β-unsaturated esters via N-Heterocyclic Carbene (NHC) catalysis is disclosed. This catalytically generated nucleophilic γ-carbon undergoes highly enantioselective additions to hydrazones. The resulting δ-lactam products can be readily transformed to optically enriched pipecolic acid derivatives. PMID:24067098

  2. Bifunctional N-heterocyclic carbene-catalyzed highly enantioselective synthesis of spirocyclic oxindolo-β-lactams.

    PubMed

    Zhang, Han-Ming; Gao, Zhong-Hua; Ye, Song

    2014-06-01

    The N-heterocyclic carbene-catalyzed Staudinger reaction of ketenes with isatin-derived ketimines was investigated. The bifunctional NHCs with a free hydroxyl group were demonstrated as efficient catalysts for the reaction, giving the corresponding spirocyclic oxindolo-β-lactams in high yields with excellent diastereo- and enantioselectivities. PMID:24856000

  3. Highly Enantioselective Direct Alkylation of Arylacetic Acids with Chiral Lithium Amides as Traceless Auxiliaries

    PubMed Central

    Stivala, Craig E.; Zakarian, Armen

    2012-01-01

    A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable. PMID:21744818

  4. Combining silver- and organocatalysis: an enantioselective sequential catalytic approach towards pyrano-annulated pyrazoles.

    PubMed

    Hack, Daniel; Chauhan, Pankaj; Deckers, Kristina; Mizutani, Yusuke; Raabe, Gerhard; Enders, Dieter

    2015-02-11

    A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a silver salt, provides a new series of chiral pyrano-annulated pyrazole derivatives in excellent yields (up to 95%) and high enantioselectivities (up to 97% ee). PMID:25564304

  5. Diastereo- and enantioselective synthesis of (E)-2-Methyl-1,2-syn- and (E)-2-Methyl-1,2-anti-3-pentenediols via allenylboronate kinetic resolution with ((d)Ipc)2BH and aldehyde allylboration.

    PubMed

    Han, Jeng-Liang; Chen, Ming; Roush, William R

    2012-06-15

    Enantioselective hydroboration of racemic allenylboronate (±)-1 with 0.48 equiv of ((d)Ipc)(2)BH at -25 °C proceeds with efficient kinetic resolution and provides allylborane (R)-Z-4. When heated to 95 °C, allylborane (R)-Z-4 isomerizes to the thermodynamically more stable allylborane isomer (S)-E-7. Subsequent allylboration of aldehydes with (R)-Z-4 or (S)-E-7 at -78 °C followed by oxidative workup provides 1,2-syn- or 1,2-anti-diols, 2 or 3, respectively, in 87-94% ee. PMID:22646839

  6. Enantioselective gas chromatography/mass spectrometry of methylsulfonyl PCBs with application to arctic marine mammals.

    PubMed

    Wiberg, K; Letcher, R; Sandau, C; Duffe, J; Norstrom, R; Haglund, P; Bidleman, T

    1998-09-15

    Four different commercially available cyclodextrin (CD) capillary gas chromatography (GC) columns were tested for the enantioselective separation of nine environmentally persistent atropisomeric 3- and 4-methylsulfonyl PCBs (MeSO2-CBs). The selected columns contained cyclodextrins with various cavity diameters (beta- or gamma-CD), which were methylated and/or tert-butyldimethylsilylated (TBDMS) in the 2,3,6-O-positions. The beta-CD column with TBDMS substituents in all of the 2,3,6-O-positions was by far the most selective column for the MeSO2-CBs tested. Enantiomers of congeners with 3-MeSO2 substitution were more easily separated than those with 4-MeSO2 substitution. The separation also seemed to be enhanced for congeners with the chlorine atoms on the non-MeSO2-containing ring and clustered on one side of the same ring. The 2,3-di-O-methyl-6-O-TBDMS-beta-CD was found to give somewhat better selectivity than the corresponding gamma-CD, in comparison between the two columns, which were identical in all other respects. Enantioselective analysis of arctic ringed seal (Phoca hispida) and polar bear (Ursus maritimus) adipose tissue revealed a strong dominance of certain enantiomers. For example, the enantiomer ratio (ER) of 3-MeSO2-CB149 was 0.32 and < 0.1 in ringed seal blubber and polar bear fat, respectively. These low ER values are indicative of highly enantioselective formation, enantioselective metabolism, enantioselective transport across cell membranes, or a combination of the three in both species. Comparable results for the enantiomeric analysis of MeSO2-CBs in biotic tissue extracts were obtained using two highly selective mass spectrometric techniques, ion trap mass spectrometry/mass spectrometry and electron capture negative ion low-resolution mass spectrometry. PMID:9751025

  7. Enantioselective degradation and chiral stability of the herbicide fluazifop-butyl in soil and water.

    PubMed

    Qi, Yanli; Liu, Donghui; Luo, Mai; Jing, Xu; Wang, Peng; Zhou, Zhiqiang

    2016-03-01

    The stereoselective degradation and transformation of the enantiomers of the herbicide fluazifop-butyl in soil and water were studied to investigate the environmental behavior and chiral stability of the optical pure product. Its main chiral metabolite fluazifop was also monitored. LC/MS/MS with Chiralpak IC chiral column was used to separate the enantiomers of fluazifop-butyl and fluazifop. Validated enantioselective residue analysis methods were established with recoveries ranging from 77.1 to 115.4% and RSDs from 0.85 to 8.9% for the enantiomers. It was found the dissipation of fluazifop-butyl was rapid in the three studied soils (Beijing, Harbin and Anhui soil), and the degradation half-lives of the enantiomers ranged from 0.136 to 2.7 d. Enantioselective degradations were found in two soils. In Beijing soil, R-fluazifop-butyl was preferentially degraded leading to relative enrichment of S-enantiomer, but in Anhui soil, S-fluazifop-butyl dissipated faster. There was no conversion of the R-fluazifop-butyl into S-fluazifop-butyl or vice versa in the soils. The formation of fluazifop in the soils was rapidly accompanied with the fast degradation of fluazifop-butyl, and the enantioselectivity and the transformation of S-fluazifop to R-fluazifop were found. The degradation of fluazifop-butyl in water was also quick, with half-lives of the enantiomers ranging from 0.34 to 2.52 d, and there was no significant enantioselectivity of the degradation of fluazifop-butyl and the formation of fluazifop. The effects of pH on the degradation showed fluazifop-butyl enantiomers degraded faster in alkaline conditions. This study showed an evidence of enantioselective behavior and enantiomerization of the chiral herbicide fluazifop-butyl. PMID:26735732

  8. Enantioselective hydrogenation. III. Methyl pyruvate hydrogenation catalyzed by alkaloid-modified iridium

    SciTech Connect

    Simons, K.E.; Johnston, P.; Plum, H.; Wells, P.B.; Ibbotson, A.

    1994-12-01

    Enantioselective hydrogenation of methyl pyruvate, MeCOCOOMe to methyl lactate, MeCH(OH)COOMe, is catalyzed in solution at room temperature by supported iridium catalysts modified with cinchona alkaloids. Modification with cinchonidine or quinine yields R-lactate in excess, whereas modification with cinchonine or quinidine favors S-lactate formation. Ir/SiO{sub 2} catalysts (20%) calcined at 393 to 573 K and reduced at 523 to 593 K were highly active for racemic hydrogenation in the absence of a modifier (rates typically 1.8 mol h{sup -1} g{sub cat}{sup -1}) and were comparably active when modified with cinchonidine but gave an enantiomeric excess of about 30%. Use of higher calcination or reduction temperatures led to substantially inferior activity and selectivity. The high rates recorded for both racemic and enantioselective reactions are dependent on the catalysts being activated before use by a procedure involving exposure of the catalyst to air after the initial reduction. Use of a Cl-free precursor gave an Ir/SiO{sub 2} catalyst (20%) of superior activity but inferior enantioselectivity. Ir/CaCO{sub 3} (5%) was more active for racemic hydrogenation than for enantioselective hydrogenation, but provided the highest value of the enantiomeric excess 39%. Kinematics of reaction are reported. Exchange of H for D in 10,11-dihydrocinchonidine at room temperature over Ir/CaCO{sub 3} occurred in the quinoline moiety but not in the quinuclidine ring system, indicating that the alkaloid was adsorbed to the Ir surface via the interaction of its {pi}-electron system. For both silica-supported and calcium carbonate-supported Ir, the presence of chloride ion in the catalyst was advantageous for the achievement of enantioselectivity. 25 refs., 2 figs., 3 tabs.

  9. Exploring the Enantioselective Mechanism of Halohydrin Dehalogenase from Agrobacterium radiobacter AD1 by Iterative Saturation Mutagenesis

    PubMed Central

    Guo, Chao; Chen, Yanpu; Zheng, Yu; Zhang, Wei; Tao, Yunwen; Feng, Juan

    2015-01-01

    Halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) shows great potential in producing valuable chiral epoxides and β-substituted alcohols. The wild-type (WT) enzyme displays a high R-enantiopreference toward most aromatic substrates, whereas no S-selective HheC has been reported to date. To obtain more enantioselective enzymes, seven noncatalytic active-site residues were subjected to iterative saturation mutagenesis (ISM). After two rounds of screening aspects of both activity and enantioselectivity (E), three outstanding mutants (Thr134Val/Leu142Met, Leu142Phe/Asn176His, and Pro84Val/Phe86Pro/Thr134Ala/Asn176Ala mutants) with divergent enantioselectivity were obtained. The two double mutants displayed approximately 2-fold improvement in R-enantioselectivity toward 2-chloro-1-phenylethanol (2-CPE) without a significant loss of enzyme activity compared with the WT enzyme. Strikingly, the Pro84Val/Phe86Pro/Thr134Ala/Asn176Ala mutant showed an inverted enantioselectivity (from an ER of 65 [WT] to an ES of 101) and approximately 100-fold-enhanced catalytic efficiency toward (S)-2-CPE. Molecular dynamic simulation and docking analysis revealed that the phenyl side chain of (S)-2-CPE bound at a different location than that of its R-counterpart; those mutations generated extra connections for the binding of the favored enantiomer, while the eliminated connections reduced binding of the nonfavored enantiomer, all of which could contribute to the observed inverted enantiopreference. PMID:25681194

  10. Enantioselective toxicities of chiral ionic liquids 1-alkyl-3-methylimidazolium lactate to aquatic algae.

    PubMed

    Chen, Hui; Zou, Yuqin; Zhang, Lijuan; Wen, Yuezhong; Liu, Weiping

    2014-09-01

    With the wide application of chiral ionic liquids (CILs) as green solvents, their threats to the aquatic environment cannot be ignored. Thus, risk assessment and the prospective design of inherently safe CILs have become more urgent. However, whether enantioselectivity is a feature of the aquatic toxicity of CILs is poorly understood. Herein, we describe the first investigation into the ecotoxicities of CILs toward green algae Scenedesmus obliquus and Euglena gracilis. A series of methylimidazolium lactic ionic liquids, which cation parts with different alkyl chains and anion part is enantiomers of lactate, are used as representative CILs. The results of S. obliquus showed that the EC50 value of L-(+)-1-ethyl-3-methylimidazolium lactate (L-(+)-EMIM L) was more than 5000 μM, while the EC50 value of D-(-)-1-ethyl-3-methylimidazolium lactate (D-(-)-EMIM L) was 2255.21 μM. Such a distinct difference indicates the enantioselective toxicity of CILs to algae. This enantioselectivity initially persisted with increasing carbon chain length, but no longer exhibited when with greater carbon chain lengths, due to changes in the toxicity weightings of the cation parts. Further research showed that the enantioselective effects of CILs resulted from the differences in the production of reactive oxygen species, the damage to cell membrane integrity and cell wall after exposure to CILs. Results from this study showed that monitoring for the racemate CILs will give an inadequate or misleading environmental risk assessment. Thus, we should improve our ability to predict their effects in natural environments. In the meantime, non-selective use of CILs will do harm to aquatic organisms. Therefore, to minimize their potential for environmental impact, the enantioselective toxicities of CILs with short alkyl chains should be taken into consideration. PMID:24880783

  11. Enantioselective 1,3-dipolar cycloaddition of nitrones to methacrolein catalyzed by (eta5-C5Me5)M{(R)-prophos} containing complexes (M = Rh, Ir; (R)-prophos = 1,2-bis(diphenylphosphino)propane): on the origin of the enantioselectivity.

    PubMed

    Carmona, Daniel; Lamata, M Pilar; Viguri, Fernando; Rodríguez, Ricardo; Oro, Luis A; Lahoz, Fernando J; Balana, Ana I; Tejero, Tomás; Merino, Pedro

    2005-09-28

    The rhodium and iridium Lewis-acid cations [(eta(5)-C(5)Me(5))M{(R)-Prophos}(H(2)O)](2+) ((R)-Prophos = 1,2-bis(diphenylphosphino)propane) efficiently catalyze the enantioselective 1,3-dipolar cycloaddition of nitrones to methacrolein. Reactions occur with perfect endo selectivity and with enantiomeric excesses up to 96%. Intermediates [(eta(5)-C(5)Me(5))M{(R)-Prophos}(methacrolein)](SbF(6))(2) (M = Rh (3), Ir (4)) have been spectroscopically and crystallographically characterized. The nitrone complexes [(eta(5)-C(5)Me(5))M{(R)-Prophos}(nitrone)](SbF(6))(2) (M = Rh, nitrone = 1-pyrrolidine N-oxide (5), 2,3,4,5,-tetrahydropyridine N-oxide (6), 3,4-dihydroisoquinoline N-oxide (7); M = Ir, nitrone = 1-pyrrolidine N-oxide (8)) have been isolated and characterized including the X-ray crystal structure of compounds 6 and 8. The equilibrium between methacrolein and nitrone complexes is also studied. [Ir]-adduct complexes are detected by (31)P NMR spectroscopy. A catalytic cycle involving [M]-methacrolein, [M]-nitrone, as well as [M]-adduct species is proposed, the first complex being the true catalyst. The absolute configuration of the adduct 4-methyl-2-N,3-diphenyl-isoxazolidine-4-carbaldehyde (9) was determined through its (S)-(-)-alpha-methylbenzylamine derivative diastereomer. Structural parameters strongly suggest that the disposition of the methacrolein in 3 and 4 is fixed by CH/pi attractive interactions between the pro-S phenyl ring of the Ph(2)PCH(CH(3)) moiety of the (R)-Prophos ligand and the CHO aldehyde proton. Proton NMR data indicate that this conformation is maintained in solution. From the structural data and the results of catalysis the origin of the enantioselectivity is discussed. PMID:16173773

  12. Insight into the stereospecificity of short-chain thermus thermophilus alcohol dehydrogenase showing pro-S hydride transfer and prelog enantioselectivity.

    PubMed

    Pennacchio, Angela; Giordano, Assunta; Esposito, Luciana; Langella, Emma; Rossi, Mosè; Raia, Carlo A

    2010-04-01

    The stereochemistry of the hydride transfer in reactions catalyzed by NAD(H)-dependent alcohol dehydrogenase from Thermus thermophilus HB27 was determined by means of (1)H-NMR spectroscopy. The enzyme transfers the pro-S hydrogen of [4R-(2)H]NADH and exhibits Prelog specificity. Enzyme-substrate docking calculations provided structural details about the enantioselectivity of this thermophilic enzyme. These results give additional insights into the diverse active site architectures of the largely versatile short-chain dehydrogenase superfamily enzymes. A feasible protocol for the synthesis of [4R-(2)H]NADH with high yield was also set up by enzymatic oxidation of 2-propanol-d(8) catalyzed by Bacillus stearothermophilus alcohol dehydrogenase. PMID:19807673

  13. N-Heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals with aldimines: highly enantioselective synthesis of dihydropyridinones.

    PubMed

    Gao, Zhong-Hua; Chen, Xiang-Yu; Zhang, Han-Ming; Ye, Song

    2015-08-01

    The N-heterocyclic carbene-catalyzed [3+3] cyclocondensation of bromoenals and aldimines was developed to give the corresponding dihydropyridinones in good yields with excellent enantioselectivities. PMID:26121224

  14. Catalytic Enantioselective Peroxidation of α, β-Unsaturated Aldehydes for the Asymmetric Synthesis of Biologically Important Chiral Endoperoxides

    PubMed Central

    Hu, Lin; Lu, Xiaojie; Deng, Li

    2015-01-01

    We have developed an unprecedented highly enantioselective catalytic peroxidation of enals. Critical to this development is the discovery that varying the structure of the hydroperoxides has a significant impact on the enantioselectivity of the organocatalytic asymmetric peroxidation. This novel transformation enabled the development of the enantioselective route toward the core structure shared by all members of the stolonoxides family of anticancer natural products, a connected trans-3,6-disubstituted-1,2-dioxane and trans-2,5-disubstituted-tetrahydrofuran ring system. Our route also features an unprecedented cyclization cascade of a chiral bis(epoxy)hydroperoxide. The new methodology and synthetic strategy established from the current studies should be applicable to the enantioselective synthesis of a broad range of chiral 1,2-dioxolanes and 1, 2-dioxanes, thereby facilitating the biological and medicinal chemistry studies of peroxy natural products. PMID:26101971

  15. Enantioselective assembly of amphipathic chiral polymer and racemic chiral small molecules during preparation of micro-scale polymer vesicles.

    PubMed

    Wang, Yingjue; Zhuang, Yiwei; Gao, Jiangang; Zou, Gang; Zhang, Qijin

    2016-03-14

    Enantioselective assembly is observed during preparation of vesicles from a solution mixture of an amphipathic block copolymer bearing pendent chiral l- or d-phenylalanine groups in hydrophobic segments and racemic chiral small molecules. Primary experimental results reveal that racemic chiral small molecules have been enantioselectively encapsulated into the hydrophobic shells of assembled vesicles with homochiral bilayer membrane structure, showing reverse CD signals compared with the original vesicles. A further study shows that the enantiomeric excess obtained through the enantioselective assembly is directly dependent on the molecular weight of the hydrophobic chiral chain segments, implying both the hydrophobic interaction and chirality are key points during the assembly of vesicles. Other factors, such as hydrogen-bonding interactions and π-π stacking interaction, are also found to be responsible for the enantioselective assembly phenomenon during the formation of the vesicles. PMID:26853976

  16. Unusual Allylpalladium Carboxylate Complexes: Identification of the Resting State of Catalytic Enantioselective Decarboxylative Ketone Allylic Alkylation Reactions**

    PubMed Central

    Sherden, Nathaniel H.; Behenna, Douglas C.; Virgil, Scott C.

    2010-01-01

    Palladium poprocks: Hold on to your CO2! Enantioselective Pd-catalyzed decarboxylative alkylation of ketone enolates proceeds via η1-σ-allyl Pd-carboxylate complexes by slow loss of CO2. PMID:19672907

  17. Dynamic Kinetic Resolution of Biaryl Lactones via a Chiral Bifunctional Amine Thiourea-Catalyzed Highly Atropo-enantioselective Transesterification.

    PubMed

    Yu, Chenguang; Huang, He; Li, Xiangmin; Zhang, Yueteng; Wang, Wei

    2016-06-01

    A solution to the unmet synthetic challenge of achieving highly atropo-enantioselective transesterification of Bringmann's lactones has been realized, employing a chiral bifunctional amine thiourea as promoter. The synergistic activation of the lactones and alcohols/phenols by the respective thiourea and amine groups is crucial for achieving the highly enantioselective, high-yielding dynamic kinetic resolution process. This protocol gives highly optically pure, axially chiral biaryl compounds with a broad substrate scope under mild reaction conditions. PMID:27218264

  18. Enantioselective Steglich Rearrangement of Oxindole Derivatives by Easily Accessible Chiral N,N-4-(Dimethylamino)pyridine Derivatives.

    PubMed

    Mandai, Hiroki; Fujiwara, Takuma; Noda, Katsuaki; Fujii, Kazuki; Mitsudo, Koichi; Korenaga, Toshinobu; Suga, Seiji

    2015-09-18

    Chiral N,N-4-(dimethylamino)pyridine (DMAP) derivatives, which can be readily prepared by the Ugi multicomponent reaction in a one-pot manner, have been efficiently applied to the enantioselective Steglich rearrangement of oxindole derivatives to give the desired products bearing a quaternary carbon center in high yield (>98% yield) and with high enantioselectivity (up to 99:1 er). PMID:26356582

  19. Hydroxymethylation beyond Carbonylation: Enantioselective Iridium-Catalyzed Reductive Coupling of Formaldehyde with Allylic Acetates via Enantiotopic π-Facial Discrimination.

    PubMed

    Garza, Victoria J; Krische, Michael J

    2016-03-23

    Chiral iridium complexes modified by SEGPHOS catalyze the 2-propanol-mediated reductive coupling of branched allylic acetates 1a-1o with formaldehyde to form primary homoallylic alcohols 2a-2o with excellent control of regio- and enantioselectivity. These processes, which rely on enantiotopic π-facial discrimination of σ-allyliridium intermediates, represent the first examples of enantioselective formaldehyde C-C coupling beyond aldol addition. PMID:26958737

  20. Enantioselective construction of a 2,2'-bisindolylmethane scaffold via catalytic asymmetric reactions of 2-indolylmethanols with 3-alkylindoles.

    PubMed

    Gong, Yu-Xin; Wu, Qiong; Zhang, Hong-Hao; Zhu, Qiu-Ning; Shi, Feng

    2015-08-01

    A chiral phosphoric acid-catalyzed asymmetric reaction of 2-indolylmethanols with 3-alkylindoles has been established, which constructed a biologically important 2,2'-bisindolylmethane scaffold in high yields and good enantioselectivities (up to 98% yield, 94:6 er). This protocol not only provides an efficient method for constructing a 2,2'-bisindolylmethane framework in an enantioselective form, but also promotes the development of 2-indolylmethanol-involved catalytic asymmetric transformations. PMID:26111901

  1. Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols.

    PubMed

    Yu, Feng; Zhou, Ji-Ning; Zhang, Xi-Chang; Sui, Yao-Zong; Wu, Fei-Fei; Xie, Lin-Jie; Chan, Albert S C; Wu, Jing

    2011-12-01

    In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2)·H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting β-, γ- or δ-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched β-halo alcohols into the corresponding styrene oxide, β-amino alcohol, and β-azido alcohol, respectively. PMID:22065457

  2. Enantioselective synthesis of chiral isotopomers of 1-alkanols by a ZACA-Cu-catalyzed cross-coupling protocol.

    PubMed

    Xu, Shiqing; Oda, Akimichi; Negishi, Ei-ichi

    2014-12-01

    Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non-measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1-alkanols, with ≥99 % enantiomeric excess (ee), by the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu-catalyzed cross-coupling reactions. ZACA-in situ iodinolysis of allyl alcohol and ZACA-in situ oxidation of TBS-protected ω-alkene-1-ols protocols were applied to the synthesis of both (R)- and (S)-difunctional intermediates with 80-90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase-catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1-alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium-labeled groups by Cu-catalyzed cross-coupling reactions without epimerization. PMID:25351794

  3. Organocatalytic asymmetric addition of naphthols and electron-rich phenols to isatin-derived ketimines: highly enantioselective construction of tetrasubstituted stereocenters.

    PubMed

    Montesinos-Magraner, Marc; Vila, Carlos; Cantón, Rubén; Blay, Gonzalo; Fernández, Isabel; Muñoz, M Carmen; Pedro, José R

    2015-05-18

    A quinine-derived thiourea organocatalyst promoted the highly enantioselective addition of naphthols and activated phenols to ketimines derived from isatins. The reaction afforded chiral 3-amino-2-oxindoles with a quaternary stereocenter in high yields (up to 99%) with excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this transformation is the first highly enantioselective addition of naphthols to ketimines. PMID:25845341

  4. γ-Carbon Activation through N-Heterocyclic Carbene/Brønsted Acids Cooperative Catalysis: A Highly Enantioselective Route to δ-Lactams.

    PubMed

    Xiao, Yonglong; Wang, Jinxin; Xia, Wenjing; Shu, Shuangjie; Jiao, Shenchao; Zhou, Yu; Liu, Hong

    2015-08-01

    A γ-carbon activation method that operates through N-heterocyclic carbene/Brønsted acid cooperative catalysis for highly enantioselective synthesis of δ-lactams is reported. The protocol allows the challenging remote γ-carbon control of regioselectivity and enantioselectivity through introduction of an appropriate γ-leaving group in the enals. The reaction offers good yields and excellent enantioselectivities, and the resulting cyclic products can be easily converted into high-value drug-like derivatives. PMID:26213807

  5. Facile Synthesis of Naphthoquinone Spiroketals by Diastereoselective Oxidative [3 + 2] Cycloaddition

    PubMed Central

    Wu, Kun-Liang; Wilkinson, Stephanie; Reich, Norbert O.; Pettus, Thomas R. R.

    2008-01-01

    A highly selective oxidative [3 + 2] cycloaddition of chiral enol ethers and hydroxynaphthoquinone is described. This convergent strategy is amenable to an enantioselective synthesis of β-rubromycin and related naphthoquinone spiroketals. Several compounds were found to inhibit DNA-polymerase and telomerase in a manner resembling α-rubromycin and β-rubromycin. PMID:18044909

  6. A Powerful Chiral Phosphoric Acid Catalyst for Enantioselective Mukaiyama-Mannich Reactions.

    PubMed

    Zhou, Fengtao; Yamamoto, Hisashi

    2016-07-25

    A new BINOL-derived chiral phosphoric acid bearing 2,4,6-trimethyl-3,5-dinitrophenyl substituents at the 3,3'-positions was developed. The utility of this chiral phosphoric acid is demonstrated by a highly enantioselective (ee up to >99 %) and diastereoselective (syn/anti up to >99:1) asymmetric Mukaiyama-Mannich reaction of imines with a wide range of ketene silyl acetals. Moreover, this method was successfully applied to the construction of vicinal tertiary and quaternary stereogenic centers with excellent diastereo- and enantioselectivity. Significantly, BINOL-derived N-triflyl phosphoramide constitutes a complementary catalyst system that allows the title reaction to be applied to more challenging imines without an N-(2-hydroxyphenyl) moiety. PMID:27265881

  7. Light controlled reversible inversion of nanophosphor-stabilized Pickering emulsions for biphasic enantioselective biocatalysis.

    PubMed

    Chen, Zhaowei; Zhou, Li; Bing, Wei; Zhang, Zhijun; Li, Zhenhua; Ren, Jinsong; Qu, Xiaogang

    2014-05-21

    In this work, by utilizing photochromic spiropyrans conjugated upconversion nanophosphors, we have successfully prepared NIR/visible light tuned interfacially active nanoparticles for the formulation of Pickering emulsions with reversible inversion properties. By loading a model enantioselective biocatalytic active bacteria Alcaligenes faecalis ATCC 8750 in the aqueous phase, we demonstrated for the first time that the multifunctional Pickering emulsion not only highly enhanced its catalytic performance but also relieved the substrate inhibition effect. In addition, product recovery, and biocatalysts and colloid emulsifiers recycling could be easily realized based on the inversion ability of the Pickering emulsion. Most importantly, the utilization of NIR/visible light to perform the reversible inversion without any chemical auxiliaries or temperature variation showed little damage toward the biocatalysts, which was highlighted by the high catalytic efficiency and high enantioselectivity even after 10 cycles. The NIR/visible light controlled Pickering emulsion showed promising potential as a powerful technique for biocatalysis in biphasic systems. PMID:24784766

  8. Enantioselective Intramolecular Hydroarylation of Alkenes via Directed C-H Bond Activation

    SciTech Connect

    Harada, Hitoshi; Thalji, Reema; Bergman, Robert; Ellman, Jonathan

    2008-05-22

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe){sub 2}]{sub 2} and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.

  9. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

    NASA Astrophysics Data System (ADS)

    Behenna, Douglas C.; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E.; Virgil, Scott C.; Stoltz, Brian M.

    2012-02-01

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.

  10. Catalytic, Enantioselective, Intramolecular Carbosulfenylation of Olefins. Mechanistic Aspects: A Remarkable Case of Negative Catalysis

    PubMed Central

    2015-01-01

    In the course of developing an enantioselective, Lewis base/Brønsted acid co-catalyzed carbosulfenylation of alkenes, a seemingly impossible conundrum arose: How could a catalyst inhibit a stoichiometric reaction? Despite the observation of very good enantioselectivities, the rate of the uncatalyzed reaction (i.e., no Lewis base) was found to be comparable to or slightly faster than that of the catalyzed process. A combination of detailed kinetic and spectroscopic studies revealed that the answer is not the direct involvement of the Lewis base catalyst, but rather the secondary consequences of its conversion to the catalytically active sulfenylating agent. Generation of the chiral sulfenylating species is accompanied by the formation of equimolar amounts of sulfonate ion and phthalimide which serve to buffer the remaining Brønsted acid and thus inhibit the racemic background reaction. Thus, the actual background reaction operative under catalytic conditions is not well mimicked by simply removing the catalyst. PMID:24548006

  11. Catalytic, enantioselective, intramolecular carbosulfenylation of olefins. Mechanistic aspects: a remarkable case of negative catalysis.

    PubMed

    Denmark, Scott E; Chi, Hyung Min

    2014-03-01

    In the course of developing an enantioselective, Lewis base/Brønsted acid co-catalyzed carbosulfenylation of alkenes, a seemingly impossible conundrum arose: How could a catalyst inhibit a stoichiometric reaction? Despite the observation of very good enantioselectivities, the rate of the uncatalyzed reaction (i.e., no Lewis base) was found to be comparable to or slightly faster than that of the catalyzed process. A combination of detailed kinetic and spectroscopic studies revealed that the answer is not the direct involvement of the Lewis base catalyst, but rather the secondary consequences of its conversion to the catalytically active sulfenylating agent. Generation of the chiral sulfenylating species is accompanied by the formation of equimolar amounts of sulfonate ion and phthalimide which serve to buffer the remaining Brønsted acid and thus inhibit the racemic background reaction. Thus, the actual background reaction operative under catalytic conditions is not well mimicked by simply removing the catalyst. PMID:24548006

  12. A broadly applicable and practical oligomeric (salen) Co catalyst for enantioselective epoxide ring-opening reactions

    PubMed Central

    White, David E.; Tadross, Pamela M.; Lu, Zhe

    2014-01-01

    The (salen) Co catalyst (4a) can be prepared as a mixture of cyclic oligomers in a short, chromatography-free synthesis from inexpensive, commercially available precursors. This catalyst displays remarkable enhancements in reactivity and enantioselectivity relative to monomeric and other multimeric (salen) Co catalysts in a wide variety of enantioselective epoxide ring-opening reactions. The application of catalyst 4a is illustrated in the kinetic resolution of terminal epoxides by nucleophilic ring-opening with water, phenols, and primary alcohols; the desymmetrization of meso epoxides by addition of water and carbamates; and the desymmetrization of oxetanes by intramolecular ring opening with alcohols and phenols. The favorable solubility properties of complex 4a under the catalytic conditions facilitated mechanistic studies, allowing elucidation of the basis for the beneficial effect of oligomerization. Finally, a catalyst selection guide is provided to delineate the specific advantages of oligomeric catalyst 4a relative to (salen) Co monomer 1 for each reaction class. PMID:25045188

  13. Enantioselective desymmetrization of prochiral cyclohexanones by organocatalytic intramolecular Michael additions to α,β-unsaturated esters.

    PubMed

    Gammack Yamagata, Adam D; Datta, Swarup; Jackson, Kelvin E; Stegbauer, Linus; Paton, Robert S; Dixon, Darren J

    2015-04-13

    A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99% ee) and in good yields (60-90%). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst. PMID:25727215

  14. A Rhodium Catalyst Superior to Iridium Congeners for Enantioselective Radical Amination Activated by Visible Light.

    PubMed

    Shen, Xiaodong; Harms, Klaus; Marsch, Michael; Meggers, Eric

    2016-06-27

    A bis-cyclometalated rhodium(III) complex catalyzes a visible-light-activated enantioselective α-amination of 2-acyl imidazoles with up to 99 % yield and 98 % ee. The rhodium catalyst is ascribed a dual function as a chiral Lewis acid and, simultaneously, as a light-activated smart initiator of a radical-chain process through intermediate aminyl radicals. Notably, related iridium-based photoredox catalysts reported before were unsuccessful in this enantioselective radical C-N bond formation. The surprising preference for rhodium over iridium is attributed to much faster ligand-exchange kinetics of the rhodium complexes involved in the catalytic cycle, which is crucial to keep pace with the highly reactive and thus short-lived nitrogen-centered radical intermediate. PMID:27145893

  15. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines

    PubMed Central

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  16. Enantioselective kinetic resolution of phenylalkyl carboxylic acids using metagenome‐derived esterases

    PubMed Central

    Fernández‐Álvaro, Elena; Kourist, Robert; Winter, Julia; Böttcher, Dominique; Liebeton, Klaus; Naumer, Christian; Eck, Jürgen; Leggewie, Christian; Jaeger, Karl‐Erich; Streit, Wolfgang; Bornscheuer, Uwe T.

    2010-01-01

    Summary Enantiomerically pure β‐arylalkyl carboxylic acids are important synthetic intermediates for the preparation of a wide range of compounds with biological and pharmacological activities. A library of 83 enzymes isolated from the metagenome was searched for activity in the hydrolysis of ethyl esters of three racemic phenylalkyl carboxylic acids by a microtiter plate‐based screening using a pH‐indicator assay. Out of these, 20 enzymes were found to be active and were subjected to analytical scale biocatalysis in order to determine their enantioselectivity. The most enantioselective and also enantiocomplementary biocatalysts were then used for preparative scale reactions. Thus, both enantiomers of each of the three phenylalkyl carboxylic acids studied could be obtained in excellent optical purity and high yields. PMID:21255306

  17. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    PubMed Central

    Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

    2012-01-01

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

  18. Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines.

    PubMed

    Xu, Kun; Gilles, Thomas; Breit, Bernhard

    2015-01-01

    The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue. PMID:26137886

  19. Enantioselective [4 + 1] Annulation Reactions of α-Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles.

    PubMed

    Zheng, Peng-Fei; Ouyang, Qin; Niu, Sheng-Li; Shuai, Li; Yuan, Yi; Jiang, Kun; Liu, Tian-Yu; Chen, Ying-Chun

    2015-07-29

    Ammonium ylides have a long history in organic synthesis, but their application in asymmetric catalysis is still underdeveloped in regard to both substrate scope and reaction pathways compared with phosphorus and sulfur ylides. Here a previously unreported asymmetric [4 + 1] annulation reaction of 3-bromooxindoles and electron-deficient 1-azadienes has been developed through ammonium ylide catalysis of a newly designed 2'-methyl α-isocupreine (α-MeIC), efficiently delivering spirocyclic oxindole compounds incorporating a dihydropyrrole motif in excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this work represents the first example of asymmetric catalysis of ammonium ylides bearing α-substitutions, and the catalytic [4 + 1] annulation pathway of ammonium ylides is also unprecedented. Moreover, (1)H NMR, mass spectroscopy, and computational calculation studies were conducted, and the catalytic cycle and a tentative explanation of the enantioselective mechanism have been successfully elucidated. PMID:26151623

  20. Synergistic Ion-Binding Catalysis Demonstrated via an Enantioselective, Catalytic [2,3]-Wittig Rearrangement

    PubMed Central

    2016-01-01

    Sigmatropic rearrangements number among the most powerful complexity-building transformations in organic synthesis but have remained largely insensitive to enantioselective catalysis due to the diffuse nature of their transition structures. Here, we describe a synergistic ion-binding strategy for asymmetric catalysis of anionic sigmatropic rearrangements. This approach is demonstrated with the enantioselective [2,3]-Wittig rearrangement of α-allyloxy carbonyl compounds to afford highly enantioenriched homoallylic alcohol products. Chiral thiourea catalysts are shown to engage reactive anions and their countercations through a cooperative set of attractive, noncovalent interactions. Catalyst structure–reactivity–selectivity relationship studies and computational analyses provide insight into catalyst–substrate interactions responsible for enantioinduction and allude to the potential generality of this catalytic strategy. PMID:27413786

  1. Enantioselective Enzyme-Catalyzed Aziridination Enabled by Active-Site Evolution of a Cytochrome P450

    PubMed Central

    2015-01-01

    One of the greatest challenges in protein design is creating new enzymes, something evolution does all the time, starting from existing ones. Borrowing from nature’s evolutionary strategy, we have engineered a bacterial cytochrome P450 to catalyze highly enantioselective intermolecular aziridination, a synthetically useful reaction that has no natural biological counterpart. The new enzyme is fully genetically encoded, functions in vitro or in whole cells, and can be optimized rapidly to exhibit high enantioselectivity (up to 99% ee) and productivity (up to 1,000 catalytic turnovers) for intermolecular aziridination, demonstrated here with tosyl azide and substituted styrenes. This new aziridination activity highlights the remarkable ability of a natural enzyme to adapt and take on new functions. Once discovered in an evolvable enzyme, this non-natural activity was improved and its selectivity tuned through an evolutionary process of accumulating beneficial mutations. PMID:26405689

  2. Enantioselective decarboxylative alkylation reactions: catalyst development, substrate scope, and mechanistic studies.

    PubMed

    Behenna, Douglas C; Mohr, Justin T; Sherden, Nathaniel H; Marinescu, Smaranda C; Harned, Andrew M; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R; McFadden, Ryan M; Roizen, Jennifer L; Enquist, John A; White, David E; Levine, Samantha R; Petrova, Krastina V; Iwashita, Akihiko; Virgil, Scott C; Stoltz, Brian M

    2011-12-01

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

  3. Enantioselective Liquid-Solid Extraction (ELSE)--An Unexplored, Fast, and Precise Analytical Method.

    PubMed

    Ulatowski, Filip; Hamankiewicz, Paulina; Jurczak, Janusz

    2015-09-14

    A novel method of evaluating the enantioselectivity of chiral receptors is investigated. It involves extraction of an ionic guest in racemic form from an ion-exchange resin to the organic solvent, where it is bound by a chiral receptor. The enantioselectivity of the examined receptor is determined simply by measuring the enantiomeric excess of the extracted guest. We show that the concept is viable for neutral receptors binding chiral organic anions extracted into acetonitile. This method was determined to be more accurate and far less time-consuming than the classical titrations. Multiple racemic guests can be applied to a resin in a single experiment, giving the method a very high throughput. PMID:26263300

  4. Removal of polycyclic musks by anaerobic membrane bioreactor: biodegradation, biosorption, and enantioselectivity.

    PubMed

    Wang, Lili; Wijekoon, Kaushalya C; Nghiem, Long D; Khan, Stuart J

    2014-12-01

    This study aims to investigate the performance of anaerobic membrane bioreactor (AnMBR) for removing five polycyclic musks (PCMs), which are common active ingredients of personal care and household cleaning products. A laboratory scale AnMBR system was used in this investigation. Concentrations of the PCMs in both the liquid and biosolids phase were measured to conduct a mass balance analysis and elucidate their fate during AnMBR treatment. The AnMBR was effective for removing PCMs from the aqueous phase by a combination of biotransformation and sorption onto the biosolids. However, biotransformation was observed to be the dominant removal mechanism for all five PCMs. Enantioselective analysis of the PCMs in influent, effluent and biomass samples indicated that there was negligible enantioselectivity in the removal of these PCMs. Accordingly, all enantiomers of these PCMs can be expected to be removed by AnMBR with similar efficiency. PMID:25461940

  5. Enantioselective apoptosis induced by individual isomers of bifenthrin in Hep G2 cells.

    PubMed

    Liu, Huigang; Li, Juan

    2015-03-01

    Bifenthrin (BF) has been used in racemate for agricultural purposes against soil insects, leading to increased inputs into soil environments. However, most of the studies about the toxicology research on BF were performed in its racemic form. The aim of the present study was to evaluate the enantiomer-specific cis-BF-induced apoptosis and intracellular reactive oxygen species (ROS) generation on human hepatocarcinoma cells (Hep G2). The results of cell viability assay and cytoflow assay indicated an obvious enantioselective hepatocyte toxicity of 1S-cis-BF in Hep G2 cells. 1S-cis-BF also induced ROS production, up-regulated Bax protein expression and down-regulated Bcl-2 expression levels. The present study suggested that enantioselective toxicity should be evaluated on currently used chiral pesticides, such as synthetic pyrethroids. PMID:25748094

  6. Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams.

    PubMed

    Behenna, Douglas C; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E; Virgil, Scott C; Stoltz, Brian M

    2012-02-01

    The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures. PMID:22270628

  7. Catalytic enantioselective OFF ↔ ON activation processes initiated by hydrogen transfer: concepts and challenges.

    PubMed

    Quintard, Adrien; Rodriguez, Jean

    2016-08-18

    Hydrogen transfer initiated processes are eco-compatible transformations allowing the reversible OFF ↔ ON activation of otherwise unreactive substrates. The minimization of stoichiometric waste as well as the unique activation modes provided by these transformations make them key players for a greener future for organic synthesis. Long limited to catalytic reactions that form racemic products, considerable progress on the development of strategies for controlling diastereo- and enantioselectivity has been made in the last decade. The aim of this review is to present the different strategies that enable enantioselective transformations of this type and to highlight how they can be used to construct key synthetic building blocks in fewer operations with less waste generation. PMID:27381644

  8. Enantioselective addition of boronates to o-quinone methides catalyzed by chiral biphenols.

    PubMed

    Luan, Yi; Schaus, Scott E

    2012-12-12

    Chiral biphenols were found to catalyze the enantioselective asymmetric addition of aryl- or alkenylboronates to o-quinone methides. Substituted 2-styryl phenols were obtained in good yields (up to 95%) with high enantiomeric ratios (up to 98:2) in the presence of 10 mol % 3,3'-Br(2)-BINOL. A two-step synthesis of (S)-4-methoxydalbergione in good yield and selectivity was achieved. PMID:23206197

  9. Enantioselective Addition of Boronates to Ortho-Quinone Methides Catalyzed by Chiral Biphenols

    PubMed Central

    Luan, Yi; Schaus, Scott E.

    2014-01-01

    Chiral biphenols were found to catalyze the enantioselective asymmetric addition of aryl- or alkenyl-boronates to ortho-quinone methides. Substituted 2-styryl phenols were obtained in good yields (up to 95%) and high enantiomeric ratios (up to 98:2) in presence of 10 mol % of 3,3′-Br2-BINOL. A two step synthesis of (S)-4-Methoxy-dalbergione is achieved in good yield and selectivity. PMID:23206197

  10. Origin of enantioselectivity in benzotetramisole-catalyzed dynamic kinetic resolution of azlactones.

    PubMed

    Liu, Peng; Yang, Xing; Birman, Vladimir B; Houk, K N

    2012-07-01

    Density functional theory (DFT) calculations were performed to investigate the origins of enantioselectivity in benzotetramisole (BTM)-catalyzed dynamic kinetic resolution of azlactones. The transition states of the fast-reacting enantiomer are stabilized by electrostatic interactions between the amide carbonyl group and the acetate anion bound to the nucleophile. The chiral BTM catalyst confines the conformation of the α-carbon and the facial selectivity of the nucleophilic attack to promote such electrostatic attractions. PMID:22686505

  11. A new synthesis of pyrrolidines by way of an enantioselective Mannich/diastereoselective hydroamination reaction sequence.

    PubMed

    Vu, Jenny M Baxter; Leighton, James L

    2011-08-01

    A new two-step synthesis of highly substituted pyrrolidines has been developed. Chiral silane Lewis acid promoted enantioselective Mannich reactions of silyl ketene imines with acylhydrazones may be used to access bishomoallylic benzoic hydrazides that in turn may be cyclized to pyrrolidines by way of the thermal hydroamination reaction reported recently by Beauchemin. Importantly, excellent diastereoselectivity may be realized in the hydroamination reactions. PMID:21749067

  12. Highly diastereoselective and enantioselective formal [4 + 3] cycloaddition of donor-acceptor cyclobutanes with nitrones.

    PubMed

    Hu, Jiang-Lin; Wang, Lijia; Xu, Hao; Xie, Zuowei; Tang, Yong

    2015-06-01

    The first highly diastereoselective and enantioselective catalytic formal [4 + 3] cycloaddition of 1,1-cyclobutane diester with nitrone has been developed. Sterically hindered chiral SaBOX/Cu(II) complex promotes the reaction efficiently with a broad substrate scope, producing a range of multifunctionalized optically active 1,2-oxazepanes with excellent stereocontrol (up to >99/1 dr and 97% ee). PMID:25974724

  13. Copper-Catalyzed Borylative Aromatization of p-Quinone Methides: Enantioselective Synthesis of Dibenzylic Boronates

    PubMed Central

    2015-01-01

    In this report, we establish that DM-Segphos copper(I) complexes are efficient catalysts for the enantioselective borylation of para-quinone methides. This method provides straightforward access to chiral monobenzylic and dibenzylic boronic esters, with enantiomeric ratios up to 96:4, using a commercially available chiral phosphine. Standard manipulations of the C–B bond afford a variety of chiral diaryl derivatives. PMID:27088045

  14. Chiral phosphoric acid catalyzed enantioselective synthesis of β-amino-α,α-difluoro carbonyl compounds.

    PubMed

    Kashikura, Wataru; Mori, Keiji; Akiyama, Takahiko

    2011-04-01

    A biphenol-based chiral phosphoric acid bearing a 9-anthryl group at each of the 3,3'-positions catalyzed the asymmetric Mannich-type reaction of N-Boc imine with difluoroenol silyl ethers in the presence of MS3A in THF to afford β-amino-α,α-difluoroketones in good yields and with excellent enantioselectivities. Optically pure 3,3-difluoroazetidin-2-one was readily synthesized from the Mannich-adduct. PMID:21391557

  15. Lipase-catalyzed highly enantioselective kinetic resolution of boron-containing chiral alcohols.

    PubMed

    Andrade, Leandro H; Barcellos, Thiago

    2009-07-16

    The first application of enzymes as catalysts to obtain optically pure boron compounds is described. The kinetic resolution of boron-containing chiral alcohols via enantioselective transesterification catalyzed by lipases was studied. Aromatic, allylic, and aliphatic secondary alcohols containing a boronate ester or boronic acid group were resolved by lipase from Candida antartica (CALB), and excellent E values (E > 200) and high enantiomeric excesses (up to >99%) of both remaining substrates and acetylated product were obtained. PMID:19552446

  16. Chiral Phosphoric Acid-Catalyzed Enantioselective Formal [3+2] Cycloaddition of Azomethine Imines with Enecarbamates.

    PubMed

    Wang, Yang; Wang, Qian; Zhu, Jieping

    2016-06-01

    The first catalytic asymmetric inverse electron demand 1,3-dipolar cycloaddition of azomethine imines with enecarbamates has been developed. Isoquinoline-fused pyrazolidines containing two or three contiguous stereogenic centers were obtained in high yields with excellent regio-, diastereo-, and enantioselectivities. The pyrazolidine ring can be opened to install an aminal, α-amino nitrile, or homoallylamine function with an excellent control of the newly generated stereogenic center. Access to aminobenzo[a]quinolizidine is also documented. PMID:27135440

  17. Enantioselective Synthesis of Isoquinolines: Merging Chiral-Phosphine and Gold Catalysis.

    PubMed

    Gao, Yu-Ning; Shi, Feng-Chen; Xu, Qin; Shi, Min

    2016-05-10

    The highly enantioselective synthesis of dihydroisoquinoline derivatives from aromatic sulfonated imines tethered with an alkyne moiety, through a one-pot asymmetric relay catalysis of chiral-phosphine and gold catalysts, is reported. Enantiomerically enriched dihydroisoquinoline derivatives were afforded in good yields and good-to-excellent ee values under mild conditions, based on the asymmetric aza-Morita-Baylis-Hillman reaction. Dihydroisoquinoline derivatives containing two chiral centers were also synthesized through further transformations. PMID:26990120

  18. Iridium-Catalyzed Enantioselective Hydroalkynylation of Enamides for the Synthesis of Homopropargyl Amides.

    PubMed

    Bai, Xiao-Yan; Wang, Zi-Xuan; Li, Bi-Jie

    2016-07-25

    Reported is an iridium-catalyzed asymmetric hydroalkynylation of enamides with terminal alkynes. The reaction occurs regioselectively at the β-position of an enamide to produce homopropargyl amides. Good to high enantioselectivity was observed with an iridium complex ligated by a chiral bis(phosphine) ligand. This method provides a straightforward route to synthesize chiral homopropargyl amides with a stereocenter β to the amide. PMID:27111577

  19. L-Proline Derived Bifunctional Organocatalysts: Enantioselective Michael Addition of Dithiomalonates to trans-β-Nitroolefins.

    PubMed

    Jin, Hui; Kim, Seung Tae; Hwang, Geum-Sook; Ryu, Do Hyun

    2016-04-15

    A series of novel L-proline derived tertiary amine bifunctional organocatalysts 9 are reported, which were applied to the asymmetric Michael addition of dithiomalonates 2 to trans-β-nitroolefins 1. The reaction proceeded in high yields (up to 99%) with high enantioselectivities (up to 97% ee). The synthetic utility of this methodology was demonstrated in the short synthesis of (R)-phenibut in high yield. PMID:26989804

  20. Asymmetric Roadmap to Diverse Polycyclic Benzopyrans via Phosphine-Catalyzed Enantioselective [4 + 2]-Annulation Reaction.

    PubMed

    Danda, Adithi; Kesava-Reddy, Naredla; Golz, Christopher; Strohmann, Carsten; Kumar, Kamal

    2016-06-01

    The catalytic addition of the amino acid derived bifunctional N-acylaminophosphine to an α-substituted allene ester generated a zwitterionic dipole that engaged the vinylogous ester function of 3-cyano-chromones in a [4 + 2] annulation reaction to deliver tetrahydroxanthones embodying three consecutive chiral centers in high yields and with excellent enantioselectivities. The established asymmetric synthesis further paves the way to two different classes of complex, sp(3)-rich tetracyclic benzopyrans via efficient cascade reactions. PMID:27187586

  1. Conformational Control of Chiral Amido-Thiourea Catalysts Enables Improved Activity and Enantioselectivity.

    PubMed

    Lehnherr, Dan; Ford, David D; Bendelsmith, Andrew J; Kennedy, C Rose; Jacobsen, Eric N

    2016-07-01

    While aryl pyrrolidinoamido-thioureas derived from α-amino acids are effective catalysts in a number of asymmetric transformations, they exist as mixtures of slowly interconverting amide rotamers. Herein, the compromising role of amide bond isomerism is analyzed experimentally and computationally. A modified catalyst structure that exists almost exclusively as a single amide rotamer is introduced. This modification is shown to result in improved reactivity and enantioselectivity by minimizing competing reaction pathways. PMID:27294369

  2. Enantioselective modular synthesis of cyclohexenones: total syntheses of (+)-crypto- and (+)-infectocaryone.

    PubMed

    Franck, Géraldine; Brödner, Kerstin; Helmchen, Günter

    2010-09-01

    A modular synthesis of cyclohexenones is described and applied to the first enantioselective total syntheses of (+)-crypto- and (+)-infectocaryone. Key steps in the synthesis of cyclohexenones are an iridium-catalyzed allylic alkylation, nucleophilic allylation, and ring-closing metathesis. On the way to (+)-cryptocaryone, a catch and release strategy involving an iodolactonization/elimination and a regioselective C-acylation were used. PMID:20677804

  3. Enantioselective accumulation of chiral polychlorinated biphenyls in lotus plant (Nelumbonucifera spp.).

    PubMed

    Dai, Shouhui; Wong, Charles S; Qiu, Jing; Wang, Min; Chai, Tingting; Fan, Li; Yang, Shuming

    2014-09-15

    Enantioselective accumulation of chiral polychlorinated biphenyls (PCBs) 91, 95, 136, 149, 176 and 183 was investigated in lotus plants (Nelumbonucifera spp.) exposed to these chemicals via spiked sediment, to determine uptake and possible biotransformation for aquatic phytoremediation purposes. The concentrations of most PCBs were greatest in roots at 60 d (19.6 ± 1.51-70.6 ± 6.14 μg kg(-1)), but were greatest in stems and leaves at 120 d (25.3 ± 6.14-95.5 ± 19.4 μg kg(-1) and 17.4 ± 4.41-70.4 ± 10.4 μg kg(-1), respectively). Total amounts were greatest at 120 d and significantly higher in roots than those in stems and in leaves (1,457 ± 220-5,852 ± 735 ng, 237 ± 47.1-902 ± 184 ng and 202 ± 60.3-802 ± 90.2 ng, respectively), but represented less than 0.51% of the total mass of PCBs added to sediments, indicating that lotus plants were unlikely to remove appreciable amounts of PCBs from contaminated sediments. Racemic PCB residues in sediment indicate no enantioselective biodegradation by sedimentary microbial consortia over the entire experiment. Preferential accumulation of the (-)-enantiomers of PCBs 91, 95 and 136 were observed in roots, stems and leaves, but non-enantioselective accumulation was observed for PCBs 149, 176 and 183. These results indicate that aquatic plants can accumulate PCBs enantioselectively via root uptake, possibly by biotransformation within plant tissues as observed for terrestrial plants. This is also the first report to identify optical rotation of the atropisomers of PCBs 91 and 95. PMID:25218260

  4. Enantioselective microbial transformation of the phenylpyrazole insecticide fipronil in anoxic sediments.

    PubMed

    Jones, W Jack; Mazur, Christopher S; Kenneke, John F; Garrison, A Wayne

    2007-12-15

    Fipronil, a chiral insecticide, was biotransformed initially to fipronil sulfide in anoxic sediment slurries following a short lag period. Sulfidogenic or methanogenic sediments transformed fipronil with half-lives of approximately 35 and 40 days, respectively. In all microbially active sediment slurries tested, the transformation of fipronil to fipronil sulfide was enantioselective. In the sulfidogenic sediment slurry, the enantiomeric fraction (EF) of fipronil decreased from an initial racemic EF value of 0.46 to a value of 0.22 during the incubation period of active fipronil transformation, indicating preferential transformation of the S-(+)-enantiomer. A previously unidentified product, 5-amino1-[2,6-dichloro-4-(trifluoromethyl)-phenyl]-4-(trifluoromethylthio)-1-H-pyrazole-3-carboxyamide, or fipronil sulfide-amide, was detected in the sulfidogenic slurries and coincided with the loss of fipronil sulfide. Biota from methanogenic freshwater sediment slurries also transformed fipronil enantioselectively but with a preference for the R-(-)-enantiomer. In all microbially inhibited (autoclaved) sediment slurries tested, no changes in the enantiomeric fractions of fipronil were observed and only low levels (< 5% of the added fipronil) of the fipronil sulfide metabolite were detected. In defined (model) chemical experiments, solutions of pyrite (FeS2) and iron sulfide (FeS) non-enantioselectively transformed fipronil primarily to either 2,6-dichloro-4-(trifluoromethyl)-aniline or to fipronil sulfide and fipronil amide, respectively. This report provides the first experimental evidence of enantioselective microbial transformation of fipronil in a natural environment (soil, water, and sediment) as well as identification of a novel fipronil biotransformation product. PMID:18200855

  5. Enantioselective autocatalysis. II. Racemization studies on a 1,4-benzodiazepinooxazole derivative

    NASA Astrophysics Data System (ADS)

    Bonner, William A.

    1995-08-01

    Since the bromofluoro-1,4-benzodiazepinooxazole derivativeI may undergo spontaneous resolution on crystallization from methanol solution, it provides an ideal substrate on which to study the phenomenon of enantioselective autocatalysis involving spontaneous resolution under racemizing conditions (srurc). in order to augment the understanding of factors which might be important in such a process we have now undertaken to study the racemization ofI in more detail by observing its rate under a wide variety of experimental conditions.

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

    PubMed

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

    2015-06-15

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

  7. Enantioselective enzymatic hydrolysis of racemic drugs by encapsulation in sol-gel magnetic sporopollenin.

    PubMed

    Yilmaz, Elif

    2012-05-01

    Candida rugosa lipase was encapsulated within a sol-gel procedure and improved considerably by fluoride-catalyzed hydrolysis of mixtures of octyltriethoxysilane and tetraethoxysilane in the presence of magnetic sporopollenin. The catalytic properties of the immobilized lipases were evaluated into model reactions, i.e., the hydrolysis of p-nitrophenylpalmitate (p-NPP), and the enantioselective hydrolysis of racemic naproxen methyl ester, mandelic acid methyl ester or 2-phenoxypropionic acid methyl ester that were studied in aqueous buffer solution/isooctane reaction system. The encapsulated magnetic sporopollenin (Spo-M-E) was found to give 319 U/g of support with 342% activity yield. It has been observed that the percent activity yields and enantioselectivity of the magnetic sporopollenin encapsulated lipase were higher than that of the encapsulated lipase without support. The substrate specificity of the encapsulated lipase revealed more efficient hydrolysis of the racemic naproxen methyl ester and 2-phenoxypropionic acid methyl ester than racemic mandelic acid methyl ester. It was observed that excellent enantioselectivity (E > 400) was obtained for encapsulated lipase with magnetic sporopollenin with an ee value of S-Naproxen and R-2 phenoxypropionic acid about 98%. PMID:21932062

  8. L-ATP is recognized by some cellular and viral enzymes: does chance drive enzymic enantioselectivity?

    PubMed Central

    Verri, A; Montecucco, A; Gosselin, G; Boudou, V; Imbach, J L; Spadari, S; Focher, F

    1999-01-01

    We demonstrate that l-ATP is recognized by some enzymes that are involved in the synthesis of nucleotides and nucleic acids. l-ATP, as well as its natural d-enantiomer, acts as a phosphate donor in the reaction catalysed by human deoxycytidine kinase, whereas it is not recognized by either enantioselective human thymidine kinase or non-enantioselective herpes virus thymidine kinase. l-ATP strongly inhibits (Ki 80 microM) the synthesis of RNA primers catalysed by DNA primase associated with human DNA polymerase alpha, whereas RNA synthesis catalysed by Escherichia coli RNA polymerase is completely unaffected. Moreover, l-ATP competitively inhibits ATP-dependent T4 DNA ligase (Ki 25 microM), suggesting that it interacts with the ATP-binding site of the enzyme. Kinetic studies demonstrated that l-ATP cannot be used as a cofactor in the ligase-catalysed joining reaction. On the other hand, l-AMP is used by T4 DNA ligase to catalyse the reverse reaction, even though a high level of intermediate circular nicked DNA molecules accumulates. Our results suggest that a lack of enantioselectivity of enzymes is more common than was believed a few years ago, and, given the absence of selective constraints against l-nucleosides in Nature, this may depend on chance more than on evolutionary strategy. PMID:9895305

  9. Relaxed enantioselectivity of human mitochondrial thymidine kinase and chemotherapeutic uses of L-nucleoside analogues.

    PubMed Central

    Verri, A; Priori, G; Spadari, S; Tondelli, L; Focher, F

    1997-01-01

    Our discovery that Herpes virus thymidine kinase (TK) and cellular deoxycytidine kinase lack enantioselectivity, being able to phosphorylate both D- and L-enantiomers of the substrate, suggested the use of unnatural L-nucleoside analogues as antiviral drugs (Herpes, hepatitis and immunodeficiency viruses). Several L-nucleoside analogues have displayed a short-term cytotoxicity much lower than their corresponding D-counterpart. Since the delayed cytotoxicity of a drug often depends on its effects on mitochondrial metabolism, we have investigated the degree of enantioselectivity of human mitochondrial thymidine kinase (mt-TK). We demonstrate that mt-TK does not show an absolute enantioselectivity, being able to recognize, although with lower efficiency, the L-enantiomers of thymidine, deoxycytidine and modified deoxyuridines, such as (E)-5-(2-bromovinyl)-2'-deoxyuridine and 5-iodo-2'-deoxyuridine. Interestingly, the reported negative co-operativity of mt-TK phosphorylating beta-D-2'-deoxythymidine (D-Thd), disappears when the deoxyribose moiety has the inverted configuration, resulting in the preferential phosphorylation of d-Thd even in the presence of high concentrations of the L-enantiomer. This, coupled with the higher Km for beta-L-2'-deoxythymidine (L-Thd), makes mt-TK resistant to high concentrations of L-Thd and L-Thd analogues, minimizing the mitochondria-dependent delayed cytotoxicity that might be caused by the administration of L-nucleoside analogues as antivirals. PMID:9359870

  10. Modelling substrate specificity and enantioselectivity for lipases and esterases by substrate-imprinted docking

    PubMed Central

    Juhl, P Benjamin; Trodler, Peter; Tyagi, Sadhna; Pleiss, Jürgen

    2009-01-01

    Background Previously, ways to adapt docking programs that were developed for modelling inhibitor-receptor interaction have been explored. Two main issues were discussed. First, when trying to model catalysis a reaction intermediate of the substrate is expected to provide more valid information than the ground state of the substrate. Second, the incorporation of protein flexibility is essential for reliable predictions. Results Here we present a predictive and robust method to model substrate specificity and enantioselectivity of lipases and esterases that uses reaction intermediates and incorporates protein flexibility. Substrate-imprinted docking starts with covalent docking of reaction intermediates, followed by geometry optimisation of the resulting enzyme-substrate complex. After a second round of docking the same substrate into the geometry-optimised structures, productive poses are identified by geometric filter criteria and ranked by their docking scores. Substrate-imprinted docking was applied in order to model (i) enantioselectivity of Candida antarctica lipase B and a W104A mutant, (ii) enantioselectivity and substrate specificity of Candida rugosa lipase and Burkholderia cepacia lipase, and (iii) substrate specificity of an acetyl- and a butyrylcholine esterase toward the substrates acetyl- and butyrylcholine. Conclusion The experimentally observed differences in selectivity and specificity of the enzymes were reproduced with an accuracy of 81%. The method was robust toward small differences in initial structures (different crystallisation conditions or a co-crystallised ligand), although large displacements of catalytic residues often resulted in substrate poses that did not pass the geometric filter criteria. PMID:19493341

  11. Advances in enantioselective analysis of chiral brominated flame retardants. Current status, limitations and future perspectives.

    PubMed

    Badea, Silviu-Laurentiu; Niculescu, Violeta Carolina; Ionete, Roxana-Elena; Eljarrat, Ethel

    2016-10-01

    Enantioselective analysis is a powerful tool for the discrimination of biotic and abiotic transformation processes of chiral environmental contaminants because their environmental biodegradation is mostly stereospecific. However, it is challenging when applied to new contaminants since enantioselective analysis methods are currently available only for a limited number of compounds. The enantioselective analysis of chiral novel brominated flame retardants (NBFRs) either using gas chromatography (GC) or liquid chromatography (LC) with various chiral stationary phases (CSP) coupled with various mass spectrometric techniques was extensively discussed. The elution order of hexabromocyclododecane (HBCD) enantiomers in chiral LC was reviewed using the experimental LC data combined also with predictions from a multi-mode Hamiltonian dynamics simulation model based on interaction energies of HBCD enantiomers with β-permethylated cyclodextrin. The further development of analytical methodologies for new chiral BFRs using advanced hyphenated analytical techniques, but also the next generation mass spectrometer analyzers (i.e. GC-Qrbitrap MS-MS, LC-Qrbitrap MS-MS), will contribute to a better characterization of the transformation pathways of chiral BFRs. PMID:27265736

  12. A novel aminoalcohol modifier for the enantioselective hydrogenation of ethyl pyruvate on Pt/alumina

    SciTech Connect

    Minder, B.; Mallat, T.; Baiker, A.

    1995-07-01

    A novel chiral modifier, (R)-2-(1-pyrrolidinyl)-1-(1-naphthyl) ethanol (PNE), has been synthesised and tested in the enantioselective hydrogenation of ethyl pyruvate over Pt/alumina. An enantiomeric excess in (R)-ethyl lactate of up to 75% was achieved. The influence of solvent, pressure, temperature, and concentrations of the components (reactant, modifier, catalyst) on the reaction rate and enantiodifferentiation was investigated. Among various polar and nonpolar solvents, acetic acid was found to be most suitable for reaching good enantioselectivity. Favorable reaction conditions are 1-10 bar hydrogen pressure, 0-25{degrees}C, and a catalyst loading {ge}15 g liter{sup -1}. The efficiency of PNE is demonstrated by the very low modifier:reactant molar ratio (1:30,000) which is required to obtain maximum enantioselectivity. The performance and stability of the aminoalcohol-type modifer are compared to those of cinchona alkaloids. At low hydrogen pressure, the enantiodifferentiation of PNE is comparable to that of 10,11-dihydrocinchonidine. 39 refs., 10 figs., 1 tab.

  13. Well-defined binuclear chiral spiro copper catalysts for enantioselective N-H insertion.

    PubMed

    Zhu, Shou-Fei; Xu, Bin; Wang, Guo-Peng; Zhou, Qi-Lin

    2012-01-11

    An asymmetric N-H insertion of α-diazoesters with anilines catalyzed by well-defined copper complexes of chiral spiro bisoxazoline ligands was studied in detail. The copper-catalyzed asymmetric N-H insertion of a wide range of α-alkyl-α-diazoacetates with anilines was accomplished with excellent enantioselectivity (up to 98% ee) and provided an efficient method for the preparation of optically active α-amino acid derivatives. A correlation study of the electronic properties of the substrates with the enantioselectivity of the N-H insertion reaction supports a stepwise insertion mechanism, and the significant first-order kinetic isotope effect proves that the proton transfer is most likely the rate-limiting step. A binuclear chiral spiro copper catalyst having 14-electron copper centers, a trans coordination model, a perfect C(2)-symmetric chiral pocket, and significant Cu-Cu interaction was isolated and extensively studied. The novel structure of the binuclear chiral spiro copper catalyst leads to unique reactivity as well as enantioselectivity in the N-H insertion reaction. PMID:22066865

  14. Etoxazole is Metabolized Enantioselectively in Liver Microsomes of Rat and Human in Vitro.

    PubMed

    Yao, Zhoulin; Qian, Mingrong; Zhang, Hu; Nie, Jing; Ye, Jingqing; Li, Zuguang

    2016-09-01

    Acaricide etoxazole belongs to the ovicides/miticides diphenyloxazole class, affecting adults to lay sterile eggs by inhibiting chitin biosynthesis possibly. The reverse-phase HPLC-MS/MS method was used to determine the etoxazole enantiomers. The enantioselective degradation behavior of rac-etoxazole in liver microsomes of rat and human in vitro with NADPH was dramatically different. The t1/2 of (R)-etoxazole was 15.23 min in rat liver microsomes and 30.54 min in human liver microsomes, while 21.73 and 23.50 min were obtained for (S)-etoxazole, respectively. The Vmax of (R)-etoxazole was almost 5-fold of (S)-etoxazole in liver microsomes of rat in vitro. However, the Vmax of (S)-etoxazole was almost 2-fold of (R)-etoxazole in liver microsomes of human in vitro. The CLint of etoxazole was also shown the enantioselectivity on the contrary in liver microsomes of rat and human. These results indicated that the metabolism of two etoxazole enantiomers was selective in liver microsomes of rat and human in vitro, and enantioselectivity in the two kinds of liver microsomes was in the difference in degradation performance. The reason might be related to the composition and content involved in the enzyme system. PMID:27479246

  15. Enantioselective Characteristics and Montmorillonite-Mediated Removal Effects of α-Hexachlorocyclohexane in Laying Hens.

    PubMed

    Liu, Xueke; Shen, Zhigang; Wang, Peng; Liu, Chang; Yao, Guojun; Zhou, Zhiqiang; Liu, Donghui

    2016-06-01

    α-Hexachlorocyclohexane (α-HCH) is a chiral organochlorine pesticide that is often ubiquitously detected in various environmental matrices and may be absorbed by the human body via food consumption, with serious detriments to human health. In this study, enantioselective degradation kinetics and residues of α-HCH in laying hens were investigated after a single dose of exposure to the pesticide, whereas enantioselectivity and residues of α-HCH in eggs, droppings, and various tissues were investigated after long-term exposure. Meanwhile, montmorillonite (MMT), a feed additive with high capacity of adsorption, was investigated for its ability to remove α-HCH from laying hens. Most non-brain tissues enantioselectively accumulated (-)-α-HCH, while (+)-α-HCH was preferentially accumulated in the brain. The enantiomer fractions (EFs) in most tissues gradually decreased, implying continuous depletion of (+)-α-HCH in laying hens. After 30 days of exposure and 31 days of elimination, the concentration of α-HCH in eggs and tissues of laying hens with MMT-containing feed was lower than that with MMT-free feed, indicating the removal effects of MMT for α-HCH in laying hens. The findings presented herein suggest that modified MMT may potentially be useful in reducing the enrichment of α-HCH in laying hens and eggs, thus lowering the risk of human intake of α-HCH. PMID:27163366

  16. Enantioselective separation and zebrafish embryo toxicity of insecticide beta-cypermethrin.

    PubMed

    Xu, Chao; Tu, Wenqing; Lou, Chun; Hong, Yingying; Zhao, Meirong

    2010-01-01

    Enantioselectivity of chiral pollutants is receiving growing concern due to the difference in toxicology and environment fate between enantiomers. In this study, enantiomers of insecticide beta-cypermethrin (beta-CP) were separated on selected chiral column by HPLC, and the toxicity of enantiomers was evaluated using the zebrafish embryo-larval assays. The enantiomers of beta-CP were baseline separated on Chiralcel OD and Chiralpak AD columns and detected by circular dichroism (CD) at 236 nm. Better separation could be achieved at lower temperature (e.g., 20 degrees C) and with lower levels of polar modifiers. Pure enantiomers were obtained on Chiralcel OD. The CD spectra of enantiomers were recorded. By comparing the elution order with a previous similar study, the absolute configuration of beta-CP enantiomers was determined. The individual enantiomers were used in zebrafish embryo test, and the results showed that beta-CP enantioselectively induced yolk sac edema, pericardial edema and crooked body. The IR-cis-alphaS and 1R-trans-alphaS enantiomers showed strong developmental toxicities at concentration of 0.1 mg/L, while the 1S-cis-alphaR and 1S-trans-alphaR induced no malformations at higher concentration (e.g., 0.3 mg/L). The results suggest that the enantioselective toxicological effects of beta-CP should be considered when evaluating its ecotoxicological effects. PMID:20608511

  17. Investigation of Enantioselective Membrane Permeability of α-Lipoic Acid in Caco-2 and MDCKII Cell.

    PubMed

    Uchida, Ryota; Okamoto, Hinako; Ikuta, Naoko; Terao, Keiji; Hirota, Takashi

    2016-01-01

    α-Lipoic acid (LA) contains a chiral carbon and exists as two enantiomers (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA)). We previously demonstrated that oral bioavailability of RLA is better than that of SLA. This difference arose from the fraction absorbed multiplied by gastrointestinal availability (F(a) × F(g)) and hepatic availability (F(h)) in the absorption phase. However, it remains unclear whether F(a) and/or F(g) are involved in enantioselectivity. In this study, Caco-2 cells and Madin-Darby canine kidney strain II cells were used to assess the enantioselectivity of membrane permeability. LA was actively transported from the apical side to basal side, regardless of the differences in its steric structure. Permeability rates were proportionally increased in the range of 10-250 µg LA/mL, and the permeability coefficient did not differ significantly between enantiomers. Hence, we conclude that enantioselective pharmacokinetics arose from the metabolism (F(h) or F(g) × F(h)), and definitely not from the membrane permeation (F(a)) in the absorption phase. PMID:26821014

  18. Nickel-catalyzed oxidations: from hydrocarbons to DNA.

    PubMed

    Burrows, C J; Muller, J G; Poulter, G T; Rokita, S E

    1996-04-01

    Nickel(II) complexes of tetradentate ligands such as cyclam and salen are catalysts for olefin epoxidation using PhIO and NaOCl, respectively. In order to understand the lack of enantioselectivity observed with chiral cyclam and salen complexes, studies of DNA and RNA oxidation were carried out in which evidence for diffusible oxidants might be found. A variety of square-planar, tetradentate nickel(II) complexes were observed to mediate guanine-specific modification in the presence of KHSO5 or magnesium monoperphthalate. In particular, the cationic complex, [(2,12-dimethyl-3,7,11,17-tetraazabicyclo [11.3.1]heptadeca-1(17),2,11,13,15-pentaenato)nickel]2+, [NiCR]2+, has been studied as a probe of nucleic acid folding. The extent of guanine reaction depends upon the exposure of N7, a good transition metal binding site, thus implicating nickel-guanine binding during DNA oxidation. If this is the case, related systems should be able to confer enantioselectivity during the use of chiral nickel complexes and achiral substrates for oxidation. Mechanistic studies, including radical quenching and DNA enantioselectivity, are described and their mechanistic implications discussed. PMID:8639377

  19. Catalytic Enantioselective 1,3-Dipolar Cycloadditions of Azomethine Ylides for Biology-Oriented Synthesis

    PubMed Central

    2014-01-01

    Conspectus Cycloaddition reactions are among the most powerful methods for the synthesis of complex compounds. In particular, the development and application of the 1,3-dipolar cycloaddition, an important member of this reaction class, has grown immensely due to its powerful ability to efficiently build various five-membered heterocycles. Azomethine ylides are commonly used as dipoles for the synthesis of the pyrrolidine scaffold, which is an important motif in natural products, pharmaceuticals, and biological probes. The reaction between azomethine ylides and cyclic dipolarophiles allows access to polycyclic products with considerable complexity. The extensive application of the 1,3-dipolar cycloaddition is based on the fact that the desired products can be obtained with high yield in a regio- and stereocontrolled manner. The most attractive feature of the 1,3-dipolar cycloaddition of azomethine ylides is the possibility to generate pyrrolidines with multiple stereocenters in a single step. The development of enantioselective cycloadditions became a subject of intensive and impressive studies in recent years. Among many modes of stereoinduction, the application of chiral metal–ligand complexes has emerged as the most viable option for control of enantioselectivity. In chemical biology research based on the principle of biology-oriented synthesis (BIOS), compound collections are prepared inspired by natural product scaffolds. In BIOS, biological relevance is employed as the key criterion to generate hypotheses for the design and synthesis of focused compound libraries. In particular, the underlying scaffolds of natural product classes provide inspiration for BIOS because they define the areas of chemical space explored by nature, and therefore, they can be regarded as “privileged”. The scaffolds of natural products are frequently complex and rich in stereocenters, which necessitates the development of efficient enantioselective methodologies. This Account

  20. Catalytic enantioselective 1,3-dipolar cycloadditions of azomethine ylides for biology-oriented synthesis.

    PubMed

    Narayan, Rishikesh; Potowski, Marco; Jia, Zhi-Jun; Antonchick, Andrey P; Waldmann, Herbert

    2014-04-15

    Cycloaddition reactions are among the most powerful methods for the synthesis of complex compounds. In particular, the development and application of the 1,3-dipolar cycloaddition, an important member of this reaction class, has grown immensely due to its powerful ability to efficiently build various five-membered heterocycles. Azomethine ylides are commonly used as dipoles for the synthesis of the pyrrolidine scaffold, which is an important motif in natural products, pharmaceuticals, and biological probes. The reaction between azomethine ylides and cyclic dipolarophiles allows access to polycyclic products with considerable complexity. The extensive application of the 1,3-dipolar cycloaddition is based on the fact that the desired products can be obtained with high yield in a regio- and stereocontrolled manner. The most attractive feature of the 1,3-dipolar cycloaddition of azomethine ylides is the possibility to generate pyrrolidines with multiple stereocenters in a single step. The development of enantioselective cycloadditions became a subject of intensive and impressive studies in recent years. Among many modes of stereoinduction, the application of chiral metal-ligand complexes has emerged as the most viable option for control of enantioselectivity. In chemical biology research based on the principle of biology-oriented synthesis (BIOS), compound collections are prepared inspired by natural product scaffolds. In BIOS, biological relevance is employed as the key criterion to generate hypotheses for the design and synthesis of focused compound libraries. In particular, the underlying scaffolds of natural product classes provide inspiration for BIOS because they define the areas of chemical space explored by nature, and therefore, they can be regarded as "privileged". The scaffolds of natural products are frequently complex and rich in stereocenters, which necessitates the development of efficient enantioselective methodologies. This Account highlights examples

  1. Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

    PubMed Central

    Ni, Huanzhen; Yao, Weijun

    2016-01-01

    Summary The first enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines is described. In the presence of a dipeptide phosphine catalyst, a wide range of highly functionalized cyclopentenes bearing an all-carbon quaternary center were obtained in moderate to good yields and with good to excellent enantioselectivities. PMID:26977194

  2. Bicyclic Guanidine Catalyzed Asymmetric Tandem Isomerization Intramolecular-Diels-Alder Reaction: The First Catalytic Enantioselective Total Synthesis of (+)-alpha-Yohimbine.

    PubMed

    Feng, Wei; Jiang, Danfeng; Kee, Choon-Wee; Liu, Hongjun; Tan, Choon-Hong

    2016-02-01

    Hydroisoquinoline derivatives were prepared in moderate to good enantioselectivities via a bicyclic guanidine-catalyzed tandem isomerization intramolecular-Diels-Alder (IMDA) reaction of alkynes. With this synthetic method, the first enantioselective synthesis of (+)-alpha-yohimbine was completed in 9 steps from the IMDA products. PMID:25932622

  3. Enantioselective synthesis of 1,2,4-triazolines by chiral iron(II)-complex catalyzed cyclization of α-isocyano esters and azodicarboxylates.

    PubMed

    Wang, Min; Liu, Xiaohua; He, Peng; Lin, Lili; Feng, Xiaoming

    2013-03-28

    Enantioselective cyclization of α-isocyano esters with azodicarboxylates catalyzed by Fe(II)-N,N'-dioxide complexes has been developed. Under mild conditions, a variety of 1,2,4-triazoline derivatives was obtained in high yields and enantioselectivities. PMID:23423581

  4. Cinchona alkaloid squaramide catalyzed enantioselective hydrazination/cyclization cascade reaction of α-isocyanoacetates and azodicarboxylates: synthesis of optically active 1,2,4-triazolines.

    PubMed

    Zhao, Mei-Xin; Bi, Hong-Lei; Zhou, Hao; Yang, Hui; Shi, Min

    2013-09-20

    An efficient enantioselective hydrazination/cyclization cascade reaction of α-substituted isocyanoacetates to azodicarboxylates catalyzed by Cinchona alkaloid derived squaramide catalysts has been investigated, affording the optically active 1,2,4-triazolines in excellent yields (up to 99%) and good to excellent enantioselectivities (up to 97% ee) under mild conditions. PMID:23984761

  5. N-Heterocyclic Carbene-Catalyzed [3 + 4] Annulation of Enals and Alkenyl Thiazolones: Enantioselective Synthesis of Thiazole-Fused ε-Lactones.

    PubMed

    Liang, Zhi-Qin; Yi, Liang; Chen, Kun-Quan; Ye, Song

    2016-06-01

    The bifunctional N-heterocyclic carbene catalyzed [3 + 4] annulation of enals and 5-alkenyl thiazolones was developed, giving the corresponding thiazole-fused ε-lactones in high yields with excellent diastereoselectivties and enantioselectivities. The thiazole-fused ε-lactone could be isomerized to the spirocyclic thiazolone-cyclopentanone without erosion of enantioselectivity. PMID:27159734

  6. Organocatalytic enantioselective decarboxylative reaction of malonic acid half thioesters with cyclic N-sulfonyl ketimines by using N-heteroarenesulfonyl cinchona alkaloid amides.

    PubMed

    Nakamura, Shuichi; Sano, Masahide; Toda, Ayaka; Nakane, Daisuke; Masuda, Hideki

    2015-03-01

    The organocatalytic enantioselective decarboxylative Mannich reaction of malonic acid half thioesters (MAHTs) with cyclic N-sulfonyl ketimines by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. The reaction proceeds through a nucleophilic addition of the MAHTs to the ketimines prior to decarboxylation. PMID:25614368

  7. An asymmetric assembly of spirooxindole dihydropyranones through a direct enantioselective organocatalytic vinylogous aldol-cyclization cascade reaction of 3-alkylidene oxindoles with isatins.

    PubMed

    Han, Jeng-Liang; Chang, Chia-Hao

    2016-02-01

    A highly enantioselective organocatalytic vinylogous aldol-cyclization cascade reaction of 3-alkylidene oxindoles to isatins has been achieved by using bifunctional organocatalysts. The unexpected intramolecular lactonization which follows the initial aldol reaction, leading to the cleavage of the oxindole ring and generation of enantioenriched spirooxindole dihydropyranones in good to excellent yields with high enantioselectivities. PMID:26728396

  8. A direct approach to amines with remote stereocenters by enantioselective CuH-catalysed reductive relay hydroamination

    PubMed Central

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L.

    2015-01-01

    Amines with remote stereocenters (stereocenters that are three or more bonds away from the C–N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here we report a copper hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters, and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original C–C double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process. PMID:26791897

  9. Enantioselective Benzylic Hydroxylation Catalysed by P450 Monooxygenases: Characterisation of a P450cam Mutant Library and Molecular Modelling.

    PubMed

    Eichler, Anja; Gricman, Łukasz; Herter, Susanne; Kelly, Paul P; Turner, Nicholas J; Pleiss, Jürgen; Flitsch, Sabine L

    2016-03-01

    Cytochrome P450 monooxygenases can catalyse the stereoselective C-H activation of a very broad range of substrates. Prediction and control of enantioselectivity of this enzyme class is of great interest for the synthesis of high-value chiral molecules. Here we have used a combination of molecular dynamics simulations and experimental screening to study the enantioselectivity of a library of active-site mutants of chimeric P450cam-RhFRed towards the benzylic hydroxylation of structurally related regioisomers of ethylmethylbenzene. Small variations either in substrate structure or in enzyme active site architecture were shown to lead to dramatic changes in enantioselectivity; this was broadly in agreement with computational predictions. In addition to validating computational approaches, these studies have provided us with a deeper understanding of effects that might control stereoselectivity in these biooxidation reactions. PMID:26698167

  10. A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination.

    PubMed

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L

    2016-02-01

    Amines with remote stereocentres (stereocentres that are three or more bonds away from the C-N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original carbon-carbon double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process. PMID:26791897

  11. Enantioselective Synthesis of α-Quaternary Mannich Adducts by Palladium-Catalyzed Allylic Alkylation: Total Synthesis of (+)-Sibirinine

    PubMed Central

    2016-01-01

    A catalytic enantioselective method for the synthesis of α-quaternary Mannich-type products is reported. The two-step sequence of (1) Mannich reaction followed by (2) decarboxylative enantioselective allylic alkylation serves as a novel strategy to in effect access asymmetric Mannich-type products of “thermodynamic” enolates of substrates possessing additional enolizable positions and acidic protons. Palladium-catalyzed decarboxylative allylic alkylation enables the enantioselective synthesis of five-, six-, and seven-membered ketone, lactam, and other heterocyclic systems. The mild reaction conditions are notable given the acidic free N–H groups and high functional group tolerance in each of the substrates. The utility of this method is highlighted in the first total synthesis of (+)-sibirinine. PMID:25578104

  12. A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination

    NASA Astrophysics Data System (ADS)

    Zhu, Shaolin; Niljianskul, Nootaree; Buchwald, Stephen L.

    2016-02-01

    Amines with remote stereocentres (stereocentres that are three or more bonds away from the C-N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original carbon-carbon double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process.

  13. Transition State Charge Stabilization Through Multiple Non-Covalent Interactions in the Guanidinium-Catalyzed Enantioselective Claisen Rearrangement

    PubMed Central

    Uyeda, Christopher; Jacobsen, Eric N.

    2011-01-01

    The mechanism by which chiral arylpyrrole-substituted guanidinium ions promote the Claisen rearrangement of O-allyl α-ketoesters and induce enantioselectivity was investigated by experimental and computational methods. In addition to stabilization of the developing negative charge on the oxallyl fragment of the rearrangement transition state by hydrogen-bond donation, evidence was obtained for a secondary attractive interaction between the π-system of a catalyst aromatic substituent and the cationic allyl fragment. Across a series of substituted arylpyrrole derivatives, enantioselectivity was observed to vary predictably according to this proposal. This mechanistic analysis led to the development of a new p-dimethylaminophenyl-substituted catalyst, which afforded improvements in enantioselectivity relative to the parent phenyl catalyst for a representative set of substrates. PMID:21391614

  14. Amine-Catalyzed Asymmetric (3 + 3) Annulations of β'-Acetoxy Allenoates: Enantioselective Synthesis of 4H-Pyrans.

    PubMed

    Ni, Chunjie; Tong, Xiaofeng

    2016-06-29

    The asymmetric (3 + 3) annulations of β'-acetoxy allenoates with either 3-oxo-nitriles or pyrazolones have been realized by using 6'-deoxy-6'-[(l)-N,N-(2,2'-oxidiethyl)-valine amido]quinine (6h) as the catalyst. The three functions of catalyst 6h, including Lewis base (quinuclidine N), H-bond donor (amide NH), and Brønsted base (morpholine N), cooperatively take crucial roles on the chemo- and enantioselectivity, allowing for the construction of 4H-pyran and 4H-pyrano[2,3-c]pyrazole in high yields and enantioselectivity. PMID:27310820

  15. Copper-Catalyzed Intramolecular Desymmetric Aryl C-O Coupling for the Enantioselective Construction of Chiral Dihydrobenzofurans and Dihydrobenzopyrans.

    PubMed

    Yang, Wenqiang; Liu, Yangyuan; Zhang, Shasha; Cai, Qian

    2015-07-20

    O-Heterocyclic structures such as 2,3-dihydrobenzofurans are key motifs in many natural compounds and pharmaceuticals. Enantioselective formation of chiral dihydrobenzofurans and analogues was achieved through a copper-catalyzed desymmetrization strategy with a chiral cyclic 1,2-diamine. A broad range of substrates are compatible with this Cu(I)-diamine catalytic system and afford the desired coupling products with chiral tertiary or quaternary carbon centers in high yields and good to excellent enantioselectivities under mild conditions. PMID:26060986

  16. Enantioselective Alkynylation of 2-Trifluoroacetyl Imidazoles Catalyzed by Bis-Cyclometalated Rhodium(III) Complexes Containing Pinene-Derived Ligands.

    PubMed

    Zheng, Yu; Harms, Klaus; Zhang, Lilu; Meggers, Eric

    2016-08-16

    Chiral rhodium(III) complexes containing two cyclometalating 2-phenyl-5,6-(S,S)-pinenopyridine ligands and two additional acetonitriles are introduced as excellent catalysts for the highly enantioselective alkynylation of 2-trifluoroacetyl imidazoles. Whereas the ligand-based chirality permits the straightforward synthesis of the complexes in a diastereomerically and enantiomerically pure fashion, the metal-centered chirality is responsible for the asymmetric induction over the course of the catalysis. For comparison, the analogous iridium congeners provide only low enantioselectivity, and previously reported benzoxazole- and benzothiazole-based catalysts do not show any catalytic activity for this reaction under standard reaction conditions. PMID:27312941

  17. Regioconvergent and Enantioselective Rhodium-Catalyzed Hydroamination of Internal and Terminal Alkynes: A Highly Flexible Access to Chiral Pyrazoles.

    PubMed

    Haydl, Alexander M; Hilpert, Lukas J; Breit, Bernhard

    2016-05-01

    The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with internal and terminal alkynes features an utmost chemo-, regio-, and enantioselective access to enantiopure allylic pyrazoles, readily available for incorporation in small-molecule pharmaceuticals. This methodology is distinguished by a broad substrate scope, resulting in a remarkable compatability with a variety of different functional groups. It furthermore exhibits an intriguing case of regio-, position-, and enantioselectivity in just one step, underscoring the sole synthesis of just one out of up to six possible products in a highly flexible approach to allylated pyrazoles by emanating from various internal and terminal alkynes. PMID:26990445

  18. A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

    PubMed Central

    Wu, Jeffrey; Wang, Yi-Ming; Drljevic, Amela; Rauniyar, Vivek; Phipps, Robert J.; Toste, F. Dean

    2013-01-01

    We report a catalytic enantioselective electrophilic fluorination of alkenes to form tertiary and quaternary C(sp3)-F bonds and generate β-amino- and β-aryl-allylic fluorides. The reaction takes advantage of the ability of chiral phosphate anions to serve as solid–liquid phase transfer catalysts and hydrogen bond with directing groups on the substrate. A variety of heterocyclic, carbocyclic, and acyclic alkenes react with good to excellent yields and high enantioselectivities. Further, we demonstrate a one-pot, tandem dihalogenation–cyclization reaction, using the same catalytic system twice in series, with an analogous electrophilic brominating reagent in the second step. PMID:23922394

  19. Copper(I)-catalyzed enantioselective nucleophilic borylation of aldehydes: an efficient route to enantiomerically enriched α-alkoxyorganoboronate esters.

    PubMed

    Kubota, Koji; Yamamoto, Eiji; Ito, Hajime

    2015-01-14

    The first catalytic enantioselective nucleophilic borylation of a C═O double bond has been achieved. A series of aldehydes reacted with a diboron reagent in the presence of a copper(I)/DTBM-SEGPHOS complex catalyst using MeOH as a proton source to give the corresponding optically active α-alkoxyorganoboronate esters with excellent enantioselectivities. Furthermore, the products could be readily converted to the corresponding functionalized chiral alcohol derivatives through stereospecific C-C bond forming reactions involving the stereogenic C-B bond. PMID:25494834

  20. Copper(I)-catalyzed enantioselective incorporation of ketones to cyclic hemiaminals for the synthesis of versatile alkaloid precursors.

    PubMed

    Shi, Shi-Liang; Wei, Xiao-Feng; Shimizu, Yohei; Kanai, Motomu

    2012-10-17

    A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Brønsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids. PMID:23039221

  1. Zn-Catalyzed Diastereo- and Enantioselective Cascade Reaction of 3-Isothiocyanato Oxindoles and 3-Nitroindoles: Stereocontrolled Syntheses of Polycyclic Spirooxindoles.

    PubMed

    Zhao, Jian-Qiang; Wu, Zhi-Jun; Zhou, Ming-Qiang; Xu, Xiao-Ying; Zhang, Xiao-Mei; Yuan, Wei-Cheng

    2015-10-16

    A catalytic asymmetric Michael/cyclization cascade reaction of 3-isothiocyanato oxindoles and 3-nitroindoles has been disclosed with a chiral Zn(OTf)2/diphenylamine-linked bis(oxazoline) complex as the catalyst. A range of enantioenriched polycyclic spirooxindole derivatives containing three contiguous stereocenters were efficiently constructed in quantitative yields with excellent diastereo- and enantioselectivities. Importantly, the metal catalytic strategy in this work is significantly superior to the previous organocatalytic method in the diastereo- and enantioselectivities for almost all of the examined cases. PMID:26412346

  2. Enantioselective Synthesis of Quaternary Carbon Stereocenters: Addition of 3-Substituted Oxindoles to Vinyl Sulfone Catalyzed by Pentanidiums.

    PubMed

    Zong, Lili; Du, Shubo; Chin, Kek Foo; Wang, Chao; Tan, Choon-Hong

    2015-08-01

    A pentanidium-catalyzed highly enantioselective conjugate addition of 3-alkyloxindoles to phenyl vinyl sulfone has been demonstrated. This approach allows the construction of 3,3-dialkyl-substituted oxindole frameworks with high yield and excellent enantioselectivity (up to 99%) under simple phase-transfer conditions. A variety of oxindoles bearing all-carbon quaternary stereogenic centers were obtained in the presence of 0.25 mol% pentanidium. Meanwhile, practicality was illustrated by a gram-scale asymmetric synthesis of two 3,3-dialkyl-substituted oxindoles. The resulting adduct can be smoothly transformed to the natural product analogue in a short synthetic route. PMID:26179829

  3. Enantioselective Rh-Catalyzed Carboacylation of C═N Bonds via C-C Activation of Benzocyclobutenones.

    PubMed

    Deng, Lin; Xu, Tao; Li, Hongbo; Dong, Guangbin

    2016-01-13

    Herein we describe the first enantioselective Rh-catalyzed carboacylation of oximes (imines) via C-C activation. In this transformation, the benzocyclobutenone C1-C2 bond is selectively activated by a low valent rhodium catalyst and subsequently the resulting two Rh-C bonds add across a C═N bond, which provides a unique approach to access chiral lactams. A range of polycyclic nitrogen-containing scaffolds were obtained in good yields with excellent enantioselectivity. Further derivatization of the lactam products led to a rapid entry to various novel fused heterocycles. PMID:26674855

  4. Enantioselective Palladium-Catalyzed Oxidative β,β-Fluoroarylation of α,β-Unsaturated Carbonyl Derivatives.

    PubMed

    Miró, Javier; Del Pozo, Carlos; Toste, F Dean; Fustero, Santos

    2016-07-25

    The site-selective palladium-catalyzed three-component coupling of deactivated alkenes, arylboronic acids, and N-fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step-economical approach to the stereoselective β-fluorination of α,β-unsaturated systems. PMID:27272390

  5. Crystal structure of the hexachlorocyclohexane dehydrochlorinase (LinA-type2): mutational analysis, thermostability and enantioselectivity.

    PubMed

    Macwan, Ankit S; Kukshal, Vandna; Srivastava, Nidhi; Javed, Saleem; Kumar, Ashwani; Ramachandran, Ravishankar

    2012-01-01

    Hexachlorocyclohexane dehydrochlorinase (LinA) mediates dehydrochlorination of γ-HCH to 1, 3, 4, 6-tetrachloro-1,4-cyclohexadiene that constitutes first step of the aerobic degradation pathway. We report the 3.5 Å crystal structure of a thermostable LinA-type2 protein, obtained from a soil metagenome, in the hexagonal space group P6(3)22 with unit cell parameters a = b = 162.5, c = 186.3 Å, respectively. The structure was solved by molecular replacement using the co-ordinates of LinA-type1 that exhibits mesophile-like properties. Structural comparison of LinA-type2 and -type1 proteins suggests that thermostability of LinA-type2 might partly arise due to presence of higher number of ionic interactions, along with 4% increase in the intersubunit buried surface area. Mutational analysis involving the differing residues between the -type1 and -type2 proteins, circular dichroism experiments and functional assays suggest that Q20 and G23 are determinants of stability for LinA-type2. It was earlier reported that LinA-type1 exhibits enantioselectivity for the (-) enantiomer of α-HCH. Contrastingly, we identified that -type2 protein prefers the (+) enantiomer of α-HCH. Structural analysis and molecular docking experiments suggest that changed residues K20Q, L96C and A131G, vicinal to the active site are probably responsible for the altered enantioselectivity of LinA-type2. Overall the study has identified features responsible for the thermostability and enantioselectivity of LinA-type2 that can be exploited for the design of variants for specific biotechnological applications. PMID:23209726

  6. Iridium-catalyzed enantioselective hydrogenation of imines in supercritical carbon dioxide

    SciTech Connect

    Kainz, S.; Brinkmann, A.; Leitner, W.; Pfaltz, A.

    1999-07-14

    Supercritical carbon dioxide (scCO{sub 2}) was shown to be a reaction medium with unique properties for highly efficient iridium-catalyzed enantioselective hydrogenation of prochiral imines. Cationic iridium(I) complexes with chiral phosphinodihydrooxazoles, modified with perfluoroalkyl groups in the ligand or in the anion, were synthesized and tested in the hydrogenation of N-(1-phenylethylidene)aniline. Both the side chains and the lipophilic anions increased the solubility, but the choice of the anion also had a dramatic effect on the enantioselectivity with tetrakis-3,5-bis(trifluoromethyl)phenylborate (BARF) leading to the highest asymmetric induction. (R)-N-phenyl-1-phenylethylamine was formed quantitatively within 1 h in scCO{sub 2}[d(CO{sub 2}) = 0.75 g mL{sup {minus}1}] at 40 C and a H{sub 2} pressure of 30 bar with enantiomeric excesses of up to 81% using 0.078 mol % catalyst. The use of scCO{sub 2} instead of conventional solvents such as CH{sub 2}Cl{sub 2} allowed the catalyst loading to be lowered significantly owing to a change in the rate profile of the reaction. the homogeneous nature of the catalytically active species under the reaction conditions was demonstrated and was found to depend strongly on the composition of the reaction mixture and especially on the presence of the substrate. Utilizing the selective extractive properties of scCO{sub 2}, the product could be readily separated from the catalyst, which could be recycled several times without significant loss of activity and enantioselectivity. High-pressure FT-IR and NMR investigations revealed that the reactivity of the products to form the corresponding carbamic acids plays an important role for the application of this new methodology.

  7. 3D chiral nanoplasmonics: fabrication, chiroptic engineering, mechanism, and application in enantioselection (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Huang, Zhifeng

    2015-09-01

    Chirality does naturally exist, and the building blocks of life (e.g. DNA, proteins, peptides and sugars) are usually chiral. Chirality inherently imposes chemical/biological selectivity on functional molecules; hence the discrimination in molecular chirality from an enantiomer to the other mirror image (i.e. enantioselection) has fundamental and application significance. Enantiomers interact with left and right handed circularly polarized light in a different manner with respect to optical extinction; hence, electronic circular dichroism (ECD) has been widely used for enantioselection. However, enantiomers usually have remarkably low ECD intensity, mainly owing to the small electric transition dipole moment induced by molecular sizes compared to the ECD-active wavelength in the UV-visible-near IR region. To enhance ECD magnitude, recently it has being developed 3D chiral nanoplasmonic structures having a helical path, and the dimensions are comparable to the ECD wavelength. However, it is still ambiguous the origin of 3D chiroplasmonics, and there is a lack of studying the interaction of 3D chiroplasmoncs with enantiomers for the application of enantioselection. Herein, we will present a one-step fabrication of 3D silver nanospirals (AgNSs) via low-substrate-temperature glancing angle deposition. AgNSs can be deposited on a wide range of substrates (including transparent and flexible substrates), in an area on the order of cm2. A set of spiral dimensions (such as spiral pitches, number of turns and handedness) have been easily engineered to tune the chiroptic properties, leading to studying the chiroplasmonic principles together with finite element simulation and the LC model. At the end, it will be demonstrated that 3D chiroplasmonics can differentiate molecular chirality of enantiomers with dramatic enhancement in the anisotropy g factor. This study opens a door to sensitively discriminate enantiomer chirality.

  8. Enantioselective developmental toxicity and immunotoxicity of pyraclofos toward zebrafish (Danio rerio).

    PubMed

    Zhuang, Shulin; Zhang, Zhisheng; Zhang, Wenjing; Bao, Lingling; Xu, Chao; Zhang, Hu

    2015-02-01

    Pyraclofos, a relatively new organophosphorus pesticide, has shown potential ecotoxicities, however, its aquatic toxicity, especially enantioselective aquatic toxicity, remains largely unknown. Using zebrafish (Danio rerio) as a preeminent vertebrate aquatic model, the enantioselective differences in the developmental toxicity and immunotoxicity of pyraclofos were evaluated. Following 96-h exposure, pyraclofos enantiomers exhibited acute toxicity and showed lethal concentration 50 of 2.23 and 3.99 mg/L for (R)-Pyraclofos and (S)-Pyraclofos, respectively. Exposure to pyraclofos caused time- and concentration-dependent malformations such as pericardial edema, yolk sac edema, crooked bodies and hatching during the embryonic development, with markedly higher percentages of malformation at higher concentrations. The concentration-dependent immunotoxicity to zebrafish embryo exposed to low level pyraclofos was induced with significant up-regulation of mRNA levels of immune-related interleukin-1β (IL-1β) gene. (R)-Pyraclofos was consistently more toxic than (S)-Pyraclofos for the acute toxicity, developmental toxicity and immunotoxicity to zebrafish. Molecular dynamics simulations revealed that at the atomic level, (R)-Pyraclofos binds more potently to IL-1β protein than (S)-Pyraclofos. This enantioselective binding is mainly contributed by the distinct binding mode of pyraclofos enantiomers and their electrostatic interactions with IL-1β, which potentially affects IL-1β-dependent proinflammatory signal transduction. Our in vitro and in silico studies provided a better insight into the molecular basis for aquatic toxicity and thus improved the risk assessment for pyraclofos and other chiral organophosphorus pesticides. PMID:25540855

  9. An enantioselective NADP(+)-dependent alcohol dehydrogenase responsible for cooxidative production of (3S)-5-hydroxy-3-methyl-pentanoic acid.

    PubMed

    Takeda, Minoru; Matsumura, Aline Tiemi; Kurosaki, Kaishi; Chhetri, Rajan Thapa; Motomatsu, Shigekazu; Suzuki, Ichiro; Sahabi, Danladi Mahuta

    2016-06-01

    A soil bacterium, Mycobacterium sp. B-009, is able to grow on racemic 1,2-propanediol (PD). The strain was revealed to oxidize 3-methyl-1,5-pentanediol (MPD) to 5-hydroxy-3-methyl-pentanoic acid (HMPA) during growth on PD. MPD was converted into an almost equimolar amount of the S-form of HMPA (S-HMPA) at 72%ee, suggesting the presence of an enantioselective MPD dehydrogenase (MPD-DH). As expected, an NADP(+)-dependent alcohol dehydrogenase, which catalyzes the initial step of MPD oxidation, was detected and purified from the cell-free extract. This enzyme was suggested to be a homodimeric medium-chain alcohol dehydrogenase/reductase (MDR). The catalytic and kinetic parameters indicated that MPD is the most suitable substrate for the enzyme. The enzyme was encoded by a 1047-bp gene (mpd1) and several mycobacterial strains were found to have putative MDR genes similar to mpd1. In a phylogenetic tree, MPD-DH formed an independent clade together with the putative MDR of Mycobacterium neoaurum, which produces opportunistic infections. PMID:26923741

  10. Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

    PubMed Central

    He, Qing; Zhan, Gu; Du, Wei

    2016-01-01

    Summary 7-Azaisatin and 7-azaoxindole skeletons are valuable building blocks in diverse biologically active substances. Here 7-azaisatins turned out to be more efficient electrophiles than the analogous isatins in the enantioselective Morita–Baylis–Hillman (MBH) reactions with maleimides using a bifunctional tertiary amine, β-isocupreidine (β-ICD), as the catalyst. This route allows a convenient approach to access multifunctional 3-hydroxy-7-aza-2-oxindoles with high enantiopurity (up to 94% ee). Other types of activated alkenes, such as acrylates and acrolein, could also be efficiently utilized. PMID:26977190

  11. Ni-Catalyzed Enantioselective C-Acylation of α-Substituted Lactams.

    PubMed

    Hayashi, Masaki; Bachman, Shoshana; Hashimoto, Satoshi; Eichman, Chad C; Stoltz, Brian M

    2016-07-27

    A new strategy for catalytic enantioselective C-acylation to generate α-quaternary-substituted lactams is reported. Ni-catalyzed three-component coupling of lactam enolates, benzonitriles, and aryl halides produces β-imino lactams that then afford β-keto lactams by acid hydrolysis. Use of a readily available Mandyphos-type ligand and addition of LiBr enable the construction of quaternary stereocenters on α-substituted lactams to form β-keto lactams in up to 94% ee. PMID:27373124

  12. 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

  13. Palladium-Catalyzed Diastereo- and Enantioselective Formal [3+2]-Cycloadditions of Substituted Vinylcyclopropanes

    PubMed Central

    Trost, Barry M.; Morris, Patrick J.; Sprague, Simon J.

    2012-01-01

    We describe a palladium-catalyzed diastereo- and enantioselective formal [3+2]-cycloaddition between substituted vinyl-cyclopropanes and electron deficient olefins in the form of azlactone- and Meldrum’s acid alkylidenes to give highly-substituted cyclo-pentane products. By modulation of the electronic properties of the vinylcyclopropane and the electron-deficient olefin, high levels of stereoselectivity were obtained. The remote stereoinduction afforded by the catalyst, distal from the chiral pocket generated by the ligand, is proposed to be the result of a new mechanism invoking the Curtin-Hammett principle. PMID:23030714

  14. Rhodium-Catalyzed Enantioselective Cycloisomerization to Cyclohexenes Bearing Quaternary Carbon Centers.

    PubMed

    Park, Jung-Woo; Chen, Zhiwei; Dong, Vy M

    2016-03-16

    We report a Rh-catalyzed enantioselective cycloisomerization of α,ω-heptadienes to afford cyclohexenes bearing quaternary carbon centers. Rhodium(I) and a new SDP ligand promote chemoselective formation of a cyclohex-3-enecarbaldehyde motif that is inaccessible by the Diels-Alder cycloaddition. Various α,α-bisallylaldehydes rearrange to generate six-membered rings by a mechanism triggered by aldehyde C-H bond activation. Mechanistic studies suggest a pathway involving regioselective carbometalation and endocyclic β-hydride elimination. PMID:26953640

  15. General Stereodivergent Enantioselective Total Synthetic Approach toward Macrosphelides A-G and M.

    PubMed

    Häcker, Christine; Plietker, Bernd

    2015-08-21

    A straightforward enantioselective total synthesis algorithm for the preparation of 8 out of 13 macrosphelides within 9-11 steps starting from tert-butyl sorbate is presented. The use of a cyclic sulfate as both protecting and reactivity directing group is the key element within this algorithm. A high-pressure transesterification allows for the selective ring-enlargement of the 15-membered macrosphelides into the 16-membered counterparts. The absolute configurations of the natural products were unambiguously assigned both by the chemical synthesis and by X-ray structure analysis. PMID:26203878

  16. Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

    PubMed Central

    Bonsignore, Martina; Raimondi, Laura; Orlandi, Manuel; Celentano, Giuseppe

    2013-01-01

    Summary The behavior of readily synthesized and even commercially available (S)-proline derivatives, was studied in the trichlorosilane-mediated reduction of ketoimines. A small library of structurally and electronically modified chiral Lewis bases was considered; such compounds were shown to promote the enantioselective reduction of different substrates in good chemical yields. In the HSiCl3 addition to the model substrate N-phenylacetophenone imine, the organocatalyst of choice led to the formation of the corresponding amine with good stereoselectivity, up to 75% ee. Theoretical studies were also performed in order to elucidate the origin of the stereoselection. PMID:23616807

  17. Asymmetric hydrogenation of ketones: Tactics to achieve high reactivity, enantioselectivity, and wide scope

    PubMed Central

    Ohkuma, Takeshi

    2010-01-01

    Ru complexes with chiral diphosphines and amine-based ligands achieve high catalytic activity and enantioselectivity for the hydrogenation of ketones under neutral to slightly basic conditions. The chiral environment is controllable by changing the combination of these two ligands. A concerted six-membered transition state is proposed to be the origin of the high reactivity. The η6-arene/TsDPEN–Ru and MsDPEN–Cp*Ir catalysts effect the asymmetric reaction under slightly acidic conditions. A variety of chiral secondary alcohols are obtained in high enantiomeric excess. PMID:20228621

  18. Enantioselective synthesis of 1,2,4-triazolines catalyzed by a cinchona alkaloid-derived organocatalyst.

    PubMed

    Shao, Qian; Chen, Jiean; Tu, Meihua; Piotrowski, David W; Huang, Yong

    2013-12-01

    An enantioselective organocatalytic process for the one-step synthesis of poly-substituted 1,2,4-triazolines is reported. The heterocycle formation is believed to go through a step-wise mechanism of nucleophilic addition of an azlactone to an azodicarboxylate in the presence of an organic base catalyst, followed by a TMSCHN2 mediated heterocyclization. Both theoretical calculations and experimental evidence suggest the pre-organization of the transition state for the chirality determining step via a unique 7-membered intramolecular hydrogen bonding. PMID:24145477

  19. Enantioselective Access to Spirocyclic Sultams by Chiral Cp(x) -Rhodium(III)-Catalyzed Annulations.

    PubMed

    Pham, Manh V; Cramer, Nicolai

    2016-02-12

    Chiral spirocyclic sultams are a valuable compound class in organic and medicinal chemistry. A rapid entry to this structural motif involves a [3+2] annulation of an N-sulfonyl ketimine and an alkyne. Although the directing-group properties of the imino group for C-H activation have been exploited, the developments of related asymmetric variants have remained very challenging. The use of rhodium(III) complexes equipped with a suitable atropchiral cyclopentadienyl ligand, in conjunction with a carboxylic acid additive, enables an enantioselective and high yielding access to such spirocyclic sultams. PMID:26836575

  20. Enantioselective Copper(I)-Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters.

    PubMed

    Dasgupta, Srimoyee; Rivas, Thomas; Watson, Mary P

    2015-11-16

    An enantioselective, copper(I)-catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters has been developed. The success of this reaction relies on identification of a Cu/PyBox catalyst capable of distinguishing the faces of the diaryl-substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available, racemic ketals into high-value enantioenriched isochroman products with fully substituted stereogenic centers. High yields and enantiomeric excesses are observed for various isochroman ketals and an array of alkynes. PMID:26403641

  1. Enantioselective Total Synthesis of (+)-Steenkrotin A and Determination of Its Absolute Configuration.

    PubMed

    Pan, Saiyong; Gao, Beiling; Hu, Jialei; Xuan, Jun; Xie, Hujun; Ding, Hanfeng

    2016-01-18

    The first enantioselective total synthesis of (+)-steenkrotin A has been achieved in 18 steps and 4.2 % overall yield. The key features of the strategy entail a Rh-catalyzed O-H bond insertion followed by an intramolecular carbonyl-ene reaction, two sequential SmI2 -mediated Ueno-Stork and ketyl-olefin cyclizations, and a cascade intramolecular aldol condensation/vinylogous retro-aldol/aldol process with inversion of the relative configuration at the C7 position. The absolute configuration of (+)-steenkrotin A was determined based on the stepwise construction of the stereocenters during the total synthesis. PMID:26660855

  2. Enantioselective cross-coupling of meso-epoxides with aryl halides.

    PubMed

    Zhao, Yang; Weix, Daniel J

    2015-03-11

    The first enantioselective cross-electrophile coupling of aryl bromides with meso-epoxides to form trans-β-arylcycloalkanols is presented. The reaction is catalyzed by a combination of (bpy)NiCl2 and a chiral titanocene under reducing conditions. Yields range from 57 to 99% with 78-95% enantiomeric excess. The 30 examples include a variety of functional groups (ether, ester, ketone, nitrile, ketal, trifluoromethyl, sulfonamide, sulfonate ester), both aryl and vinyl halides, and five- to seven-membered rings. The intermediacy of a carbon radical is strongly suggested by the conversion of cyclooctene monoxide to an aryl [3.3.0]bicyclooctanol. PMID:25716775

  3. Enantioselective Organocatalytic Diels–Alder Trapping of Photochemically Generated Hydroxy‐o‐Quinodimethanes

    PubMed Central

    Dell'Amico, Luca; Vega‐Peñaloza, Alberto; Cuadros, Sara

    2016-01-01

    Abstract The photoenolization/Diels–Alder strategy offers straightforward access to synthetically valuable benzannulated carbocyclic products. This historical light‐triggered process has never before succumbed to efforts to develop an enantioselective catalytic approach. Herein, we demonstrate how asymmetric organocatalysis provides simple yet effective catalytic tools to intercept photochemically generated hydroxy‐o‐quinodimethanes with high stereoselectivity. We used a chiral organic catalyst, derived from natural cinchona alkaloids, to activate maleimides toward highly stereoselective Diels–Alder reactions. An unconventional mechanism of stereocontrol is operative, wherein the organocatalyst is actively involved in both the photochemical pathway, by leveraging the formation of the reactive photoenol, and the stereoselectivity‐defining event. PMID:26797768

  4. Enantioselective synthesis and antioxidant activity of 3,4,5-substituted piperidine derivatives.

    PubMed

    Kim, Jin Ho; Shyam, Pranab K; Kim, Mi Jeong; Lee, Hwa-Jung; Lee, Jeong Tae; Jang, Hye-Young

    2016-07-01

    In this study, 3,4,5-trisubstituted piperidines were synthesized enantioselectively, and their antioxidant activity was evaluated. The 3,4,5-trisubstituted piperidines containing TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and a spatially proximal hydroxy group showed good antioxidant activity. Some of these compounds showed IC50 values in a nanomolar range, comparable to that of TEMPO. Probably the TEMPO generated from the homolysis of the CON bond of 3,4,5-trisubstituted piperidines functions as a radical-scavenging entity, and the hydroxy group of piperidines has a synergistic effect to the antioxidant activity. PMID:27177825

  5. A Nine-Step Enantioselective Total Synthesis of (−)-Vincorine

    PubMed Central

    Horning, Benjamin D.

    2013-01-01

    A concise and highly enantioselective total synthesis of the akuammiline alkaloid (−)-vincorine has been accomplished. A key element of the synthesis is a stereoselective organocatalytic Diels–Alder, iminium cyclization cascade sequence, which serves to construct the tetracyclic alkaloid core architecture in one step from simple achiral precursors. The challenging seven-membered, azepanyl ring system is installed by way of a single electron-mediated cyclization event initiated from an acyl telluride precursor. The total synthesis of (−)-vincorine is achieved in nine steps and 9% overall yield from commercially available starting materials. PMID:23586842

  6. Cu(ii)-catalyzed enantioselective oxygen atom transfer from oxaziridine to oxindole derivatives with chiral phenanthroline.

    PubMed

    Naganawa, Yuki; Aoyama, Tomotaka; Nishiyama, Hisao

    2015-12-21

    In the presence of a Cu(ii) complex of axially chiral, N,N,O-tridentate phenanthroline ligand (S)-2, asymmetric oxygen atom transfer of oxindole derivatives (3) using Davis' oxaziridine (4) occurred to give the corresponding 3-aryl-3-hydroxy-2-oxindole derivatives (1) with excellent enantioselectivity (up to 96% ee). The X-ray crystallographic analysis of the isolated Cu(ii) complex disclosed its N,N,O-tridentate coordination, which is critical to realize effective catalytic activity. PMID:26456035

  7. Enantioselective Synthesis of 3,3-Difluoropyrrolidin-4-ol, a Valuable Building Block in Medicinal Chemistry.

    PubMed

    Si, Chong; Fales, Kevin R; Torrado, Alicia; Frimpong, Kwame; Kaoudi, Talbi; Vandeveer, Harold George; Njoroge, F George

    2016-05-20

    In this paper, we report for the first time two enantioselective routes to 4,4-difluoropyrrolidin-3-ol, a valuable building block in medicinal chemistry. In the first route, we took advantage of the C2 symmetry of (3R,4R)-3,4-dihydroxypyrrolidine in which the desired chirality was derived from the chiral pool (l-(+)-tartaric acid). In the second route, we efficiently assembled the pyrrolidine ring in the presence of a gem-difluoro moiety to avoid using potentially hazardous deoxofluorinating reagents and subsequently introduced the chirality by a stereoselective iridium-diamine-catalyzed asymmetric transfer hydrogenation reaction. PMID:27138111

  8. Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis †

    PubMed Central

    Perdicchia, Dario; Christodoulou, Michael S.; Fumagalli, Gaia; Calogero, Francesco; Marucci, Cristina; Passarella, Daniele

    2015-01-01

    2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1. PMID:26712740

  9. Enantioselective cyclopropanation of indoles: construction of all-carbon quaternary stereocenters.

    PubMed

    Özüduru, Gülsüm; Schubach, Thea; Boysen, Mike M K

    2012-10-01

    The first enantioselective copper-catalyzed cyclopropanation of N-acyl indoles is described. Using carbohydrate-based bis(oxazoline) ligands (glucoBox), the products were obtained in up to 72% ee. Cyclopropanation of N-Boc 3-methyl indole yielded a product with an all-carbon quaternary stereocenter, which is a valuable building block for the synthesis of indole alkaloids: Deprotection and rearrangement gave a tricyclic hemiaminal ester in 96% ee, which was subsequently employed as a key intermediate for the synthesis of (-)-desoxyeseroline. PMID:23009104

  10. Enantioselective Pictet-Spengler Reactions of Isatins for the Synthesis of Spiroindolones

    PubMed Central

    Badillo, Joseph J.; Silva-García, Abel; Shupe, Benjamin H.; Fettinger, James C.; Franz, Annaliese K.

    2011-01-01

    The condensation cyclization between isatins and 5-methoxy tryptamine catalyzed by chiral phosphoric acids provides spirooxindole tetrahydro-β-carboline products in excellent yields (up to 99%) and enantioselectivity (up to 98:2 er). A comparison of catalysts provides insight for the substrate scope and factors responsible for efficient catalytic activity and selectivity in the spirocyclization. Chiral phosphoric acids with different 3,3′-substitution on the binaphthyl system and opposite axial chirality afford the spiroindolone product with the same absolute configuration. PMID:22442499

  11. Enantioselective Cycloaddition of Münchnones onto [60]Fullerene: Organocatalysis versus Metal Catalysis

    PubMed Central

    2014-01-01

    Novel chiral catalytic systems based on both organic compounds and metal salts have been developed for the enantioselective [3 + 2] cycloaddition of münchnones onto fullerenes and olefins. These two different approaches proved to be efficient and complementary in the synthesis of optically active pyrrolino[3,4:1,2][60]fullerenes with high levels of enantiomeric excess and moderate to good conversions. Further functionalization of the pyrrolinofullerene carboxylic acid derivatives has been carried out by esterification and amidation reactions. PMID:24483247

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

    PubMed

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

    2016-05-01

    The asymmetric alkylation of acyclic ketones is a longstanding challenge in organic synthesis. Reported herein are 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. PMID:27038004

  13. Enantioselective Synthesis and Profiling of Two Novel Diazabicyclooctanone β-Lactamase Inhibitors

    PubMed Central

    2014-01-01

    The enantioselective synthesis of two novel cyclopropane-fused diazabicyclooctanones is reported here. Starting from butadiene monoxide, the key enone intermediate 7 was prepared in six steps. Subsequent stereoselective introduction of the cyclopropane group and further transformation led to compounds 1a and 1b as their corresponding sodium salt. The great disparity regarding their hydrolytic stability was rationalized by the steric interaction between the cyclopropyl methylene and urea carbonyl. These two novel β-lactamase inhibitors were active against class A, C, and D enzymes. PMID:25313328

  14. Enantioselective synthesis of dialkylated N-heterocycles by palladium-catalyzed allylic alkylation.

    PubMed

    Numajiri, Yoshitaka; Jiménez-Osés, Gonzalo; Wang, Bo; Houk, K N; Stoltz, Brian M

    2015-03-01

    The enantioselective synthesis of α-disubstituted N-heterocyclic carbonyl compounds has been accomplished using palladium-catalyzed allylic alkylation. These catalytic conditions enable access to various heterocycles, such as morpholinone, thiomorpholinone, oxazolidin-4-one, 1,2-oxazepan-3-one, 1,3-oxazinan-4-one, and structurally related lactams, all bearing fully substituted α-positions. Broad functional group tolerance was explored at the α-position in the morpholinone series. We demonstrate the utility of this method by performing various transformations on our useful products to readily access a number of enantioenriched compounds. PMID:25714704

  15. Oxidation catalysis via visible-light water activation of a [Ru(bpy)3](2+) chromophore BSA-metallocorrole couple.

    PubMed

    Herrero, Christian; Quaranta, Annamaria; Ricoux, Rémy; Trehoux, Alexandre; Mahammed, Atif; Gross, Zeev; Banse, Frédéric; Mahy, Jean-Pierre

    2016-01-14

    Light induced enantioselective oxidation of an organic molecule with water as the oxygen atom source is demonstrated in a system where chirality is induced by a protein, oxygen atom transfer by a manganese corrole, and photocatalysis by ruthenium complexes. PMID:26620115

  16. Rhodium-Catalyzed Atroposelective [2 + 2 + 2] Cycloaddition of Ortho-Substituted Phenyl Diynes with Nitriles: Effect of Ortho Substituents on Regio- and Enantioselectivity.

    PubMed

    Kashima, Kenichi; Teraoka, Kota; Uekusa, Hidehiro; Shibata, Yu; Tanaka, Ken

    2016-05-01

    Axially chiral 3-(2-halophenyl)pyridines were successfully synthesized in high yields with excellent enantioselectivity by the cationic rhodium(I)/(S)-H8-BINAP complex-catalyzed atroposelective [2 + 2 + 2] cycloaddition of (o-halophenyl)diynes with nitriles. Interestingly, regio- and enantioselectivity highly depend on ortho substituents on the phenyl group of diynes. When the ortho substituents were methoxy and methoxycarbonyl groups, axially chiral 3-arylpyridines were obtained as a major product, while enantioselectivity was lowered significantly. On the other hand, when the ortho substituents were alkyl groups, regioselectivity was switched to give achiral 6-arylpyridines in high yields. PMID:27074498

  17. A Chiral N,N'-Dioxide-Zn(II) Complex Catalyzes the Enantioselective [2+2] Cycloaddition of Alkynones with Cyclic Enol Silyl Ethers.

    PubMed

    Kang, Tengfei; Ge, Shulin; Lin, Lili; Lu, Yan; Liu, Xiaohua; Feng, Xiaoming

    2016-04-25

    A highly efficient enantioselective [2+2] cycloaddition between alkynones and cyclic enol silyl ethers was developed by using a chiral N,N'-dioxide-zinc(II) complex as a catalyst. This method functions well for a variety of terminal alkynes as well as cyclic enol silyl ethers, with good to excellent enantioselectivity (up to 97 % ee). This is also the first successful example for the catalytic enantioselective [2+2] cycloaddition of internal alkynes with cyclic enol silyl ethers to give fully substituted cyclobutenes. Meanwhile, the desired cyclobutene product can easily be transformed into fused cyclobutane derivatives. PMID:27059528

  18. Catalytically Asymmetric Pd/Norbornene Catalysis: Enantioselective Synthesis of (+)-Rhazinal, (+)-Rhazinilam, and (+)-Kopsiyunnanine C1-3.

    PubMed

    Zhao, Kun; Xu, Shibo; Pan, Chongqing; Sui, Xianwei; Gu, Zhenhua

    2016-08-01

    A catalytically asymmetric palladium/norbornene-catalyzed reaction is reported, where α-aryl tetrahydroquinoline derived phosphoramidite L15 is found to be the optimum ligand. Taking advantage of this transformation, the concise and unified enantioselective syntheses of (+)-rhazinal, (+)-rhazinilam, and (+)-kopsiyunnanine C1, C2, and C3 are realized. PMID:27405044

  19. Enantioselective Nickel-Catalyzed anti-Carbometallative Cyclizations of Alkynyl Electrophiles Enabled by Reversible Alkenylnickel E/Z Isomerization.

    PubMed

    Clarke, Christopher; Incerti-Pradillos, Celia A; Lam, Hon Wai

    2016-07-01

    Nickel-catalyzed additions of arylboronic acids to alkynes, followed by enantioselective cyclizations of the alkenylnickel species onto tethered ketones or enones, are reported. These reactions are reliant upon the formal anti-carbonickelation of the alkyne, which is postulated to occur by the reversible E/Z isomerization of an alkenylnickel species. PMID:27333360

  20. Combination of oxyanion Gln114 mutation and medium engineering to influence the enantioselectivity of thermophilic lipase from Geobacillus zalihae.

    PubMed

    Wahab, Roswanira Abdul; Basri, Mahiran; Rahman, Mohd Basyaruddin Abdul; Rahman, Raja Noor Zaliha Raja Abdul; Salleh, Abu Bakar; Leow, Thean Chor

    2012-01-01

    The substitution of the oxyanion Q114 with Met and Leu was carried out to investigate the role of Q114 in imparting enantioselectivity on T1 lipase. The mutation improved enantioselectivity in Q114M over the wild-type, while enantioselectivity in Q114L was reduced. The enantioselectivity of the thermophilic lipases, T1, Q114L and Q114M correlated better with log p as compared to the dielectric constant and dipole moment of the solvents. Enzyme activity was good in solvents with log p < 3.5, with the exception of hexane which deviated substantially. Isooctane was found to be the best solvent for the esterification of (R,S)-ibuprofen with oleyl alcohol for lipases Q114M and Q114L, to afford E values of 53.7 and 12.2, respectively. Selectivity of T1 was highest in tetradecane with E value 49.2. Solvents with low log p reduced overall lipase activity and dimethyl sulfoxide (DMSO) completely inhibited the lipases. Ester conversions, however, were still low. Molecular sieves employed as desiccant were found to adversely affect catalysis in the lipase variants, particularly in Q114M. The higher desiccant loading also increased viscosity in the reaction and further reduced the efficiency of the lipase-catalyzed esterifications. PMID:23109876

  1. Enantioselective synthesis of cyclopropanes that contain fluorinated tertiary stereogenic carbon centers: a chiral α-fluoro carbanion strategy.

    PubMed

    Shen, Xiao; Zhang, Wei; Zhang, Lei; Luo, Tao; Wan, Xiaolong; Gu, Yucheng; Hu, Jinbo

    2012-07-01

    Chiral transfer: the fluorinated sulfoximine (see scheme; Ts=p-toluenesulfonyl) was synthesized and used as the first chiral fluoromethylenation reagent for the synthesis of cyclopropanes that contain fluorinated tertiary stereogenic carbon centers in good yields, good diastereoselectivity, and excellent enantioselectivity. PMID:22689532

  2. Enantioselective ring-opening of meso-epoxides by aromatic amines catalyzed by a homochiral metal-organic framework.

    PubMed

    Regati, Sridhar; He, Yabing; Thimmaiah, Muralidhara; Li, Peng; Xiang, Shengchang; Chen, Banglin; Zhao, John Cong-Gui

    2013-10-28

    The enantioselective ring-opening of meso-epoxides by aromatic amines was achieved by using a new chiral metal-organic framework . The corresponding α-hydroxyamines were obtained with good yields and ee values (up to 89% ee). PMID:24030658

  3. Enantioselective Reduction by Crude Plant Parts: Reduction of Benzofuran-2-yl Methyl Ketone with Carrot ("Daucus carota") Bits

    ERIC Educational Resources Information Center

    Ravia, Silvana; Gamenara, Daniela; Schapiro, Valeria; Bellomo, Ana; Adum, Jorge; Seoane, Gustavo; Gonzalez, David

    2006-01-01

    The use of biocatalysis and biotransformations are important tools in green chemistry. The enantioselective reduction of a ketone by crude plant parts, using carrot ("Daucus carota") as the reducing agent is presented. The experiment introduces an example of a green chemistry procedure that can be tailored to fit in a regular laboratory session.…

  4. Lewis base activation of Lewis acids. Catalytic enantioselective addition of silyl enol ethers of achiral methyl ketones to aldehydes.

    PubMed

    Denmark, Scott E; Heemstra, John R

    2003-06-26

    A highly enantioselective addition of silyl enol ethers derived from simple methyl ketones is described. The catalyst system of silicon tetrachloride activated by a chiral bisphosphoramide (R,R)-7 effectively promotes the addition of a variety of unsubstituted silyl enol ethers to aromatic, olefinic, and heteroaromatic aldehydes in excellent yield. [reaction: see text] PMID:12816434

  5. Enantioselective Nickel-Catalyzed anti-Carbometallative Cyclizations of Alkynyl Electrophiles Enabled by Reversible Alkenylnickel E/Z Isomerization

    PubMed Central

    2016-01-01

    Nickel-catalyzed additions of arylboronic acids to alkynes, followed by enantioselective cyclizations of the alkenylnickel species onto tethered ketones or enones, are reported. These reactions are reliant upon the formal anti-carbonickelation of the alkyne, which is postulated to occur by the reversible E/Z isomerization of an alkenylnickel species. PMID:27333360

  6. GAS CHROMATOGRAPHIC ANALYSIS WITH CHIRAL CYCLODEXTR IN PHASES REVEALS THE ENANTIOSELECTIVE FORMATION OF HYDROXYLATED POLYCHLORINATED BIPHENYLS BY RAT LIVER MICROSOMES

    PubMed Central

    Kania-Korwel, Izabela; Duffel, Michael W.; Lehmler, Hans-Joachim

    2011-01-01

    Chiral PCB congeners are major components of PCB mixtures and undergo enantioselective biotransformation to hydroxylated (OH-)PCBs by cytochrome P450 enzymes. While it is known that biotransformation results in an enantiomeric enrichment of the parent PCB, it is currently unknown if OH-PCBs are formed enantioselectively. The present study screened seven commercial capillary gas chromatography columns containing modified β- or γ-cyclodextrins for their potential to separate the atropisomers of methylated derivatives of OH-PCB. The atropisomers of 3-, 4- and 5-methoxy derivatives were at least partially separated on one or more columns. A subsequent biotransformation study was performed with rat liver microsomes to assess if hydroxylated metabolites are formed enantioselectively from PCBs 91, 95, 132 and 149. The OH-PCBs were extracted from the microsomal incubations, derivatized with diazomethane and analyzed as the respective methoxylated (MeO-)PCB derivatives using selected columns. The 5-hydroxylated metabolites of PCBs 91, 95, 132 and 149 were the major metabolites, which is consistent with PCB’s biotransformation by cytochrome P450 2B enzymes. All 5-hydroxylated metabolites displayed a clear, congener-specific enantiomeric enrichment. Overall, this study demonstrates for the first time that chiral PCBs, such as PCB 91, 95, 132 and 149, are enantioselectively metabolized to OH-PCBs by cytochrome P450 enzymes. PMID:21966948

  7. Correction: A novel enantioselective synthesis of 6H-dibenzopyran derivatives by combined palladium/norbornene and cinchona alkaloid catalysis.

    PubMed

    Xu, Di; Dai, Li; Catellani, Marta; Motti, Elena; Della Ca', Nicola; Zhou, Zhiming

    2015-02-28

    Correction for 'A novel enantioselective synthesis of 6H-dibenzopyran derivatives by combined palladium/norbornene and cinchona alkaloid catalysis' by Di Xu et al., Org. Biomol. Chem., 2015, DOI: 10.1039/c4ob02551b. PMID:25629771

  8. Enantioselective Synthesis of 3a-Amino-Pyrroloindolines by Copper-Catalyzed Direct Asymmetric Dearomative Amination of Tryptamines.

    PubMed

    Liu, Chuan; Yi, Ji-Cheng; Zheng, Zhong-Bo; Tang, Yong; Dai, Li-Xin; You, Shu-Li

    2016-01-11

    A direct asymmetric dearomative amination of tryptamines with O-(2,4-dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr-bisoxazoline complex as a catalyst, affording 3a-amino-pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (-)-psychotriasine in a highly concise manner. PMID:26603145

  9. Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

    PubMed Central

    Zhu, Haipan; Du, Peile; Li, Jianjun; Liao, Ziyang; Liu, Guohua

    2016-01-01

    Summary A cooperative catalytic strategy of chiral iminium catalysis by regioselective activation of the C=C bond in enals and a transition metal promoting to open the 2-vinylcyclopropanes for highly regio- and enantioselective [3 + 2] cycloaddition reaction of 2-vinylcyclopropanes with α,β-unsaturated aldehydes has been developed. PMID:27559383

  10. Enantioselective Intramolecular C-H Insertion of Donor and Donor/Donor Carbenes by a Nondiazo Approach.

    PubMed

    Zhu, Dong; Ma, Jun; Luo, Kui; Fu, Hongguang; Zhang, Li; Zhu, Shifa

    2016-07-11

    The first enantioselective intramolecular C-H insertion and cyclopropanation reactions of donor- and donor/donor-carbenes by a nondiazo approach are reported. The reactions were conducted in a one-pot manner without slow addition and provided the desired dihydroindole, dihydrobenzofuran, tetrahydrofuran, and tetrahydropyrrole derivatives with up to 99 % ee and 100 % atom efficiency. PMID:27265896

  11. Enantioselective hydrolysis of epichlorohydrin using whole Aspergillus niger ZJB-09173 cells in organic solvents.

    PubMed

    Jin, Huo-Xi; Hu, Zhong-Ce; Zheng, Yu-Guo

    2012-09-01

    The enantioselective hydrolysis of racemic epichlorohydrin for the production of enantiopure (S)-epichlorohydrin using whole cells of Aspergillus niger ZJB-09173 in organic solvents was investigated. Cyclohexane was used as the reaction medium based on the excellent enantioselectivity of epoxide hydrolase from A. niger ZJB- 09173 in cyclohexane. However, cyclohexane had a negative effect on the stability of epoxide hydrolase from A. niger ZJB-09173. In the cyclohexane medium, substrate inhibition, rather than product inhibition of catalysis, was observed in the hydrolysis of racemic epichlorohydrin using A. niger ZJB-09173. The racemic epichlorohydrin concentration was markedly increased by continuous feeding of substrate without significant decline of the yield. Ultimately, 18.5% of (S)-epichlorohydrin with 98 percent enantiomeric excess from 153.6 mM of racemic epichlorohydrin was obtained by the dry cells of A. niger ZJB-09173, which was the highest substrate concentration in the production of enantiopure (S)-epichlorohydrin by epoxide hydrolases using an organic solvent medium among the known reports. PMID:22922194

  12. Evaluating the enantioselective distribution, degradation and excretion of epoxiconazole in mice following a single oral gavage.

    PubMed

    Wang, Dezhen; Qiu, Jing; Zhu, Wentao; Zhang, Ping; Deng, Nian; Wang, Xinru; Wang, Yao; Zhou, Zhiqiang

    2015-01-01

    1. The enantiomeric enrichment or degradation of epoxiconazole has been reported in grape, soil, tubifex and mealworm beetle. But, little is known about its enantioselective behaviors in mammals. 2. To further understand differences in the distribution, degradation and excretion of epoxiconazole enantiomers in vivo, male CD-1 mice were selected as the test model to investigate the enantioselective behaviors after a single oral gavage. Mice were sacrificed after 1 h, 3 h, 7 h, 12 h, 24 h, 48 h, 72 h treatment, blood, tissues and excretions were collected for epoxiconazole analysis by LC-MS/MS. 3. On the Lux-Cellulose-1 chiral column, an enrichment of the second eluting (+)-epoxiconazole was generally observed, and feces and urine showed similar EF with major tissues. 4. To elucidate the potential role of intestinal bacterial flora in stereospecific degradation of epoxiconazole, mice fecal flora were cultured in vitro and incubated with epoxiconazole for 48 h. Results showed that (-)-epoxiconazole was preferentially degraded by intestinal bacterial. 5. These results may provide useful information for risk assessment of epoxiconazole on non-target animals. PMID:26108358

  13. Acute toxicity, bioactivity, and enantioselective behavior with tissue distribution in rabbits of myclobutanil enantiomers.

    PubMed

    Sun, Mingjing; Liu, Donghui; Qiu, Xinxu; Zhou, Qian; Shen, Zhigang; Wang, Peng; Zhou, Zhiqiang

    2014-12-01

    The enantioselective bioactivity against pathogens (Cercospora arachidicola, Fulvia fulva, and Phytophthora infestans) and acute toxicity to Daphnia magna of the fungicide myclobutanil enantiomers were studied. The (+)-enantiomer in an antimicrobial activity test was about 1.79-1.96 times more active than the (-)-enantiomer. In the toxicity assay, the calculated 24-h LC50 values of the (-)-form, rac-form and (+)-form were 16.88, 13.17, and 11.91 mg/L, and the 48-h LC50 values were 10.15, 9.24, and 5.48 mg/L, respectively, showing that (+)-myclobutanil was more toxic. Meanwhile, the enantioselective metabolism of myclobutanil enantiomers following a single intravenous (i.v.) administration was investigated in rabbits. Total plasma clearance value (CL) of the (+)-enantiomer was 1.68-fold higher than its antipode. Significant differences in pharmacokinetics parameters between the two enantiomers indicated that the high bioactive (+)-enantiomer was preferentially metabolized and eliminated in plasma. Consistent consequences were found in the tissues (liver, brain, heart, kidney, fat, and muscle), resulting in a relative enrichment of the low-activity (-)-myclobutanil. These systemic assessments of the stereoisomers of myclobutanil cannot be used only to investigate environmental and biological behavior, but also have human health implications because of the long persistence of triazole fungicide and enantiomeric enrichment in mammals and humans. PMID:25043148

  14. Direct and Highly Regioselective and Enantioselective Allylation of β-Diketones

    PubMed Central

    Chalifoux, Wesley A.; Reznik, Samuel K.; Leighton, James L.

    2012-01-01

    The enantioselective allylation of ketones represents both a problem of fundamental importance in asymmetric reaction design and one of only a very small number of available methods to access valuable tertiary carbinols. Despite the vast amount of attention from chemists that this problem has elicited,1-8 however, success has generally been limited to just a few simple ketone types thus limiting the utility of these methods. A method for the selective allylation of functionally complex ketones would be expected to increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective, and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by the co-optation of their enol form to provide the necessary Brønsted acid activation. This unprecedented reaction thus not only significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed, but also overturns more than a century of received wisdom regarding the reactivity of β-diketones. PMID:22763452

  15. 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. PMID:17583959

  16. A novel control of enzymatic enantioselectivity through the racemic temperature influenced by reaction media.

    PubMed

    Jin, Xin; Liu, Bokai; Ni, Zhong; Wu, Qi; Lin, Xianfu

    2011-05-01

    The influence of reaction media on the racemic temperature (T(r)) in the lipase-catalyzed resolution of ketoprofen vinyl ester was investigated. An effective approach to the control of the enzymatic enantioselectivity and the prediction of the increasing tendency was developed based on the T(r) influenced by reaction media. The T(r) for the resolution catalyzed by Candida rugosa lipase (CRL) was found at 29 °C in aqueous and S-ketoprofen was obtained predominantly at 40 °C. However, CRL showed R-selectivity at 40 °C in diisopropyl ether because the T(r) was changed to 56 °C. CRL, lipase from AYS Amano(®) and Mucor javanicus lipase were further applied for the investigation of the enzymatic enantioselectivity in dioxane, DIPE, isooctane and their mixed media with water. The effects of the reaction medium on T(r) could be related to the solvent hydrophobicity, the lipase conformational flexibility and the interaction between the enantiomers and the lipase. PMID:22113016

  17. Bioaccumulation and enantioselectivity of type I and type II pyrethroid pesticides in earthworm.

    PubMed

    Chang, Jing; Wang, Yinghuan; Wang, Huili; Li, Jianzhong; Xu, Peng

    2016-02-01

    In this study, the bioavailability and enantioselectivity differences between bifenthrin (BF, typeⅠpyrethroid) and lambad-cyhalothrin (LCT, type Ⅱ pyrethroid) in earthworm (Eisenia fetida) were investigated. The bio-soil accumulation factors (BSAFs) of BF was about 4 times greater than that of LCT. LCT was degraded faster than BF in soil while eliminated lower in earthworm samples. Compound sorption plays an important role on bioavailability in earthworm, and the soil-adsorption coefficient (K(oc)) of BF and LCT were 22 442 and 42 578, respectively. Metabolic capacity of earthworm to LCT was further studied as no significant difference in the accumulation of LCT between the high and low dose experiment was found. 3-phenoxybenzoic acid (PBCOOH), a metabolite of LCT produced by earthworm was detected in soil. The concentration of PBCOOH at high dose exposure was about 4.7 times greater than that of in low dose level at the fifth day. The bioaccumulation of BF and LCT were both enantioselective in earthworm. The enantiomer factors of BF and LCT in earthworm were approximately 0.12 and 0.65, respectively. The more toxic enantiomers ((+)-BF and (-)-LCT) had a preferential degradation in earthworm and leaded to less toxicity on earthworm for racemate exposure. In combination with other studies, a liner relationship between Log BSAF(S) and Log K(ow) was observed, and the Log BSAF(S) decreased with the increase of Log K(ow). PMID:26490429

  18. Phytotoxicity of chiral herbicide bromacil: Enantioselectivity of photosynthesis in Arabidopsis thaliana.

    PubMed

    Chen, Zunwei; Zou, Yuqin; Wang, Jia; Li, Meichao; Wen, Yuezhong

    2016-04-01

    With the wide application of chiral herbicides and the frequent detection of photosystem II (PSII) herbicides, it is of great importance to assess the direct effects of PSII herbicides on photosynthesis in an enantiomeric level. In the present study, the enantioselective phytotoxicity of bromacil (BRO), typical photosynthesis inhibition herbicide, on Arabidopsis thaliana was investigated. The results showed that S-BRO exhibited a greater inhibition of electron transmission in photosystem I (PSI) of A. thaliana than R-BRO by inhibiting the transcription of fnr 1. S-BRO also changed the chlorophyll fluorescence parameters Y (II), Y (NO), and Y (NPQ) to a greater extent than R-Bro. Transcription of genes psbO2, Lhcb3 and Lhcb6 was down-regulated in an enantioselective rhythm and S-BRO caused more serious influence, indicating that S-BRO did worse damage to the photosystem II (PSII) of A. thaliana than R-BRO. This study suggested that S-BRO disturbed the photosynthesis of plants to a larger extent than R-BRO and provided a new sight to evaluate the phytotoxicity of chiral herbicides. PMID:26802342

  19. The chiral separation and enantioselective degradation of the chiral herbicide napropamide.

    PubMed

    Qi, Yanli; Liu, Donghui; Sun, Mingjing; Di, Shanshan; Wang, Peng; Zhou, Zhiqiang

    2014-02-01

    The chiral pesticide enantiomers often have different toxic effects and environmental behaviors, which suggests that the risk assessments should be on an enantiomeric level. In this work, the chiral separation of the napropamide enantiomers and the stereoselective degradation in tomato, cucumber, rape, cabbage, and soil were investigated. Napropamide enantiomers could be separated absolutely by high-performance liquid chromatography (HPLC) using a Chiralpak IC column with a resolution factor of 11.75 under the optimized condition. Solid phase extraction (SPE) was used for cleanup of the enantiomers in the vegetable samples. The residue analysis method was validated. Good linearities (R(2)  = 0.9997) and recoveries (71.43% -97.64%) were obtained. The limits of detection (LOD) were 0.05 mg/kg in soil and 0.20 mg/kg in vegetables. The results of degradation showed that napropamide dissipated rapidly in vegetables with half-lives of only 1.13-2.21 days, but much more slowly in soil, with a half-life of 11.95 d. Slight stereoselective degradation of the two enantiomers was only observed in cabbage, with enantiomeric fraction (EF) = 0.46, and there was no enantioselectivity in the other vegetables. The degradation of napropamide in the five matrixes was fast, and there was no enantioselectivity. PMID:24436218

  20. Enantioselective fluorescent recognition in the fluorous phase: enhanced reactivity and expanded chiral recognition.

    PubMed

    Wang, Chao; Wu, Elaine; Wu, Xuedan; Xu, Xiangchuan; Zhang, Guoqing; Pu, Lin

    2015-03-25

    A novel perfluoroalkyl-BINOL-based chiral diketone is found to be the first highly enantioselective fluorescent sensor in the fluorous phase. One enantiomer of a chiral amino alcohol or diamine at a concentration greater than 1 mM can cause an up to 1200-2000-fold fluorescent enhancement of the sensor (0.08 mM), while the other enantiomer gives only a 10-50-fold enhancement. The fluorous-phase-based sensor is found to enhance the reactivity of the previously reported fluorous insoluble sensor with amino alcohols and expand its chiral recognition ability. Dynamic light scattering studies show the formation of aggregates of very different particle sizes when two enantiomers of a substrate interact with the sensor in perfluorohexane (FC-12). This substantial difference enables easy discrimination of the enantiomers with UV-lamps or even the naked eye. NMR, IR, and mass spectroscopic studies indicate that the fluorescent enhancement and enantioselectivity should originate from the fluorous solvent-promoted nucleophilic addition of the amino alcohols to the carbonyl groups of the sensor. PMID:25761050

  1. Quantitative determination of ondansetron in human plasma by enantioselective liquid chromatography-tandem mass spectrometry.

    PubMed

    Liu, Ke; Dai, Xiaojian; Zhong, Dafang; Chen, Xiaoyan

    2008-03-15

    A sensitive and enantioselective method was developed and validated for the determination of ondansetron enantiomers in human plasma using enantioselective liquid chromatography-tandem mass spectrometry. The enantiomers of ondansetron were extracted from plasma using ethyl acetate under alkaline conditions. HPLC separation was performed on an ovomucoid column using an isocratic mobile phase of methanol-5 mM ammonium acetate-acetic acid (20:80:0.02, v/v/v) at a flow rate of 0.40 mL/min. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode, using the transitions of m/z 294-->170 for ondansetron enantiomers, and m/z 285-->124 for tropisetron (internal standard). The method was linear in the concentration range of 0.10-40 ng/mL for each enantiomer using 200 microL of plasma. The lower limit of quantification (LLOQ) for each enantiomer was 0.10 ng/mL. The intra- and inter-assay precision was 3.7-11.6% and 5.6-12.3% for R-(-)-ondansetron and S-(+)-ondansetron, respectively. The accuracy was 100.4-107.1% for R-(-)-ondansetron and 103.3-104.9% for S-(+)-ondansetron. No chiral inversion was observed during the plasma storage, preparation and analysis. The method was successfully applied to characterize the pharmacokinetic profiles of ondansetron enantiomers in healthy volunteers after an intravenous infusion of 8 mg racemic ondansetron. PMID:18299256

  2. Enantioselective bioactivity, acute toxicity and dissipation in vegetables of the chiral triazole fungicide flutriafol.

    PubMed

    Zhang, Qing; Hua, Xiu-de; Shi, Hai-yan; Liu, Ji-song; Tian, Ming-ming; Wang, Ming-hua

    2015-03-01

    The enantioselective bioactivity, acute toxicity and stereoselective degradation of the chiral triazole fungicide flutriafol in vegetables were investigated for the first time using the (R)-, (S)- and rac-flutriafol. The order of the bioactivity against five target pathogens (Rhizoctonia solani, Alternaria solani, Pyricularia grisea, Gibberella zeae, Botrytis cinerea) was found to be (R)-flutriafol>rac-flutriafol>(S)-flutriafol. The fungicidal activity of (R)-flutriafol was 1.49-6.23 times higher than that of (S)-flutriafol. The (R)-flutriafol also showed 2.17-3.52 times higher acute toxicity to Eisenia fetida and Scenedesmus obliquus than (S)-flutriafol. The stereoselective degradation of flutriafol in tomato showed that the active (R)-flutriafol degraded faster, resulting in an enrichment of inactive (S)-form, and the half-lives were 9.23 d and 10.18 d, respectively. Inversely, the (S)-flutriafol, with a half-life of 4.76 d, was preferentially degraded in cucumber. In conclusion, the systemic assessments of the triazole fungicide flutriafol stereoisomers on the enantioselective bioactivity, acute toxicity and environmental behavior may have implications for better environmental and ecological risk assessment. PMID:25463219

  3. Are Nutrient Stresses Associated with Enantioselectivity of the Chiral Herbicide Imazethapyr in Arabidopsis thaliana?

    PubMed

    Chen, Zunwei; Chen, Hui; Zou, Yuqin; Qiu, Jiguo; Wen, Yuezhong; Xu, Dongmei

    2015-12-01

    Plant growth can be inhibited by herbicides and is strongly limited by the availability of nutrients, which can influence human health through the food chain. Until now, however, cross talk between the enantioselectivity of herbicides and nutrient stresses has been poorly understood. We analyzed trace element and macroelement contents in shoots of Arabidopsis thaliana treated by the chiral herbicide imazethapyr (IM) and observed that multiple-nutrient stress (trace elements Mn, Cu, and Fe and macroelements P, K, Ca, and Mg) was enantioselective. The (R)-IM treatments resulted in Mn 23.37%, Cu 63.53%, P 30.61%, K 63.70%, Ca 34.32%, and Mg 36.14% decreases compared with the control. Interestingly, it was also found that herbicidally active (R)-IM induced notable aggregation of nutrient elements in leaves and roots compared with the control and (S)-IM. Through gene expression analyses, it was found that herbicidally active (R)-IM induced the up- or down-regulation of genes involved in the transport of nutrient elements. We propose that (R)-IM affected the uptake and translocation of nutrient elements in A. thaliana, which destroyed the balance of nutrient elements in the plant. This finding reminds us to reconsider the effect of nutrient stresses in risk assessment of herbicides. PMID:26566036

  4. Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.

    PubMed

    Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; Lepera, José Salvador

    2013-03-01

    Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%). PMID:23362155

  5. Mechanistic Analysis and Optimization of the Copper-Catalyzed Enantioselective Intramolecular Alkene Aminooxygenation

    PubMed Central

    Paderes, Monissa C.; Keister, Jerome B.; Chemler, Sherry R.

    2013-01-01

    The catalytic asymmetric aminooxygenation of alkenes provides an efficient and straightforward approach to prepare chiral vicinal amino alcohols. We have reported a copper(II)-catalyzed enantioselective intramolecular alkene aminooxygenation, using (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as the oxygen source, which results in the synthesis of chiral indolines and pyrrolidines. Herein we disclose that kinetics studies indicate the reaction is first order both in substrate and the [Cu(R,R)-Ph-bis(oxazoline)]OTf2 catalyst, and zero order in TEMPO. Furthermore, kinetic isotope effect studies support that the cis aminocupration step, the addition of N-Cu across the alkene, is the rate-limiting step. Subsequent formation of a carbon radical intermediate, and direct carbon radical trapping with TEMPO is the indicated mechanism for the C-O bond formation as suggested by a deuterium labeling experiment. A ligand screen revealed that C(4)-phenyl substitution on the bis(oxazoline) is optimal for high asymmetric induction. The size of the substrate’s N-sulfonyl group also influences the enantioselectivity of the reaction. The preparative scale catalytic aminooxygenation reaction (gram scale) was demonstrated and an unexpected dependence on reaction temperature was uncovered on the larger scale reaction. PMID:23244027

  6. Mechanistic analysis and optimization of the copper-catalyzed enantioselective intramolecular alkene aminooxygenation.

    PubMed

    Paderes, Monissa C; Keister, Jerome B; Chemler, Sherry R

    2013-01-18

    The catalytic asymmetric aminooxygenation of alkenes provides an efficient and straightforward approach to prepare chiral vicinal amino alcohols. We have reported a copper(II)-catalyzed enantioselective intramolecular alkene aminooxygenation, using (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as the oxygen source, which results in the synthesis of chiral indolines and pyrrolidines. Herein we disclose that kinetics studies indicate the reaction is first order both in substrate and the [Cu(R,R)-Ph-bis(oxazoline)]OTf(2) catalyst and zero order in TEMPO. Furthermore, kinetic isotope effect studies support that the cis-aminocupration step, the addition of N-Cu across the alkene, is the rate-limiting step. Subsequent formation of a carbon radical intermediate and direct carbon radical trapping with TEMPO is the indicated mechanism for the C-O bond formation as suggested by a deuterium labeling experiment. A ligand screen revealed that C(4)-phenyl substitution on the bis(oxazoline) is optimal for high asymmetric induction. The size of the substrate's N-sulfonyl group also influences the enantioselectivity of the reaction. The preparative-scale catalytic aminooxygenation reaction (gram scale) was demonstrated, and an unexpected dependence on reaction temperature was uncovered on the larger scale reaction. PMID:23244027

  7. Enantioselective analysis and fate of polycyclic musks in a water recycling plant in Sydney (Australia).

    PubMed

    Wang, L; Khan, S J

    2014-01-01

    Synthetic polycyclic musks (PCMs) Galaxolide (HHCB), Tonalide (AHTN), Phantolide (AHDI), Traseolide (ATII) and Cashmeran (DPMI) are chiral chemicals that are commonly used in washing product industries as racemic mixtures. The major source of PCMs in municipal wastewater is from personal care and household products. Recent studies have shown that PCMs may enhance the relative toxicity of other environmental chemicals by inhibiting cellular xenobiotic defence systems. High sensitivity enantioselective analysis of these compounds enables improved characterisation of the environmental persistence and fate of PCMs, distinguishing between individual enantiomers so that a more complete understanding of environmental risks tributed by individual enantiomers may be obtained. Concentrations of PCMs through the various treatment stages of an advanced water recycling plant in Sydney were investigated to assess the removal of these chemicals. Average concentrations of HHCB, AHTN, AHDI, ATII and DPMI in influent were: 2,545, 301, 2, 5 and 33 ng L(-1), respectively. In the final effluent, AHDI, ATII and DPMI were not detected, while HHCB and AHTN were still measured at concentrations of 21 and 2 ng L(-1). No significant enantioselective transformation was detected during biological or advanced treatment processes. PMID:24845313

  8. Enantioselective toxicity and bioaccumulation of fipronil in fathead minnows (Pimephales promelas) following water and sediment exposures.

    PubMed

    Baird, Suzanne; Garrison, Arthur; Jones, Jack; Avants, Jimmy; Bringolf, Robert; Black, Marsha

    2013-01-01

    Fipronil is a widely used, broad-spectrum pesticide that is applied as an equal mixture of two enantiomers. As regulations on older pesticides become more stringent, production and application of fipronil is expected to grow, leading to increased inputs into aquatic environments and complex exposures to biota. To better understand the potential exposures introduced by fipronil contamination, we conducted subchronic toxicity tests with larval fathead minnows (Pimephales promelas) and waterborne fipronil and its enantiomers and exposed juvenile fathead minnows to fipronil-spiked sediment. Enantioselective toxicity was observed in fish after the 7-d subchronic exposure, with increased toxicity of the racemate and (+) enantiomer observed compared with the (-) enantiomer. Curiously, toxicities of the racemate and (+) enantiomer were not significantly different, even though the racemate contains 50% of the (+) enantiomer and 50% of the less toxic (-) enantiomer. During the sediment exposure, racemic fipronil in sediment was transformed primarily to fipronil sulfide, while exposed fish rapidly accumulated fipronil and/or fipronil sulfide and transformed the majority to fipronil sulfone. Using the results of the sediment-exposure experiment, the authors explored a mechanism that may contribute to the interesting trends in enantioselective toxicity observed during the waterborne exposures. In tandem, the aquatic toxicity experiment and the spiked sediment exposure demonstrate the potentially complex behavior of fipronil in sediment and fish. PMID:23109279

  9. Enantioselective approach to polycyclic polyprenylated acylphloroglucinols via catalytic asymmetric intramolecular cyclopropanation.

    PubMed

    Uetake, Yuta; Uwamori, Masahiro; Nakada, Masahisa

    2015-02-01

    The formal enantioselective total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of an α-diazo ketone, a common synthetic intermediate for the above four polycyclic polyprenylated acylphloroglucinols previously reported by us, exhibited low enantioselectivity. However, CAIMCP of the corresponding α-diazo β-keto sulfone afforded the desired product in 79% yield with 84% ee. Investigation of the CAIMCP of the α-diazo β-keto sulfone demonstrated the formation of a rearrangement product in the presence of molecular sieves 4 Å, whereas, in the presence of H2O, the byproduct derived from ring-opening of the desired cyclopropane was observed. X-ray crystallographic analysis suggested that the above two products are derived from the same chiral intermediate. The product derived from ring-opening of the cyclopropane was successfully transformed to the respective synthetic intermediates for the total syntheses of nemorosone, garsubellin A, clusianone, and hyperforin, which had previously been reported by us. PMID:25581002

  10. Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption

    PubMed Central

    Kasten, Chelsea R.; Blasingame, Shelby N.; Boehm, Stephen L.

    2014-01-01

    The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides “binge-like” ethanol access to mice by restricting access to a two hour period, three hours into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-hour two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)- baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)- baclofen, chronic intake was not significantly altered. S(-)- baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature. PMID:25557834

  11. Bidirectional enantioselective effects of the GABAB receptor agonist baclofen in two mouse models of excessive ethanol consumption.

    PubMed

    Kasten, Chelsea R; Blasingame, Shelby N; Boehm, Stephen L

    2015-02-01

    The GABAB receptor agonist baclofen has been studied extensively in preclinical models of alcohol-use disorders, yet results on its efficacy have been uncertain. Racemic baclofen, which is used clinically, can be broken down into separate enantiomers of the drug. Baclofen has been shown to produce enantioselective effects in behavioral assays, including those modeling reflexive and sexual behavior. The current studies sought to characterize the enantioselective effects of baclofen in two separate models of ethanol consumption. The first was a Drinking-in-the-Dark procedure that provides "binge-like" ethanol access to mice by restricting access to a 2-h period, 3 h into the dark cycle. The second was a two-bottle choice procedure that utilized selectively bred High Alcohol Preferring 1 (HAP1) mice to model chronic ethanol access. HAP1 mice are selectively bred to consume pharmacologically relevant amounts of ethanol in a 24-h two-bottle choice paradigm. The results showed that baclofen yields enantioselective effects on ethanol intake in both models, and that these effects are bidirectional. Total ethanol intake was decreased by R(+)-baclofen, while total intake was increased by S(-)-baclofen in the binge-like and chronic drinking models. Whereas overall binge-like saccharin intake was significantly reduced by R(+)-baclofen, chronic intake was not significantly altered. S(-)-baclofen did not significantly alter saccharin intake. Neither enantiomer significantly affected locomotion during binge-like reinforcer consumption. Collectively, these results demonstrate that baclofen produces enantioselective effects on ethanol consumption. More importantly, the modulation of consumption is bidirectional. The opposing enantioselective effects may explain some of the variance seen in published baclofen literature. PMID:25557834

  12. Highly Enantioselective Epoxidation of α,β-Unsaturated Ketones Catalyzed by Rare-Earth Amides [(Me3Si)2N]3RE(μ-Cl)Li(THF)3 with Phenoxy-Functionalized Chiral Prolinols.

    PubMed

    Zeng, Chao; Yuan, Dan; Zhao, Bei; Yao, Yingming

    2015-05-01

    A simple and efficient catalytic enantioselective epoxidation of α,β-unsaturated ketones has been successfully developed, which was catalyzed by rare-earth metal amides [(Me3Si)2N]3RE(μ-Cl)Li(THF)3 (RE = Yb (1), La (2), Sm (3), Y (4), Lu (5)) in the presence of phenoxy-functionalized chiral prolinols at room temperature using tert-butylhydroperoxide (TBHP) as the oxidant. The combination of an Yb-based amide 1 and a chiral proligand (S)-2,4-di-tert-butyl-6-((2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)phenol) performed very well, and both the yields and the enantiomeric excess of the chiral epoxides reached up to 99% and 99% ee. PMID:25905674

  13. Highly enantioselective synthesis of dihydrocoumarin-fused dihydropyrans via the phosphine-catalyzed [4 + 2] annulation of allenones with 3-aroylcoumarins.

    PubMed

    Han, Xiaoyu; Ni, Huanzhen; Chan, Wai-Lun; Gai, Xikun; Wang, Yongjiang; Lu, Yixin

    2016-06-14

    Phosphine-catalyzed [4 + 2] annulation between 3-aroylcoumarins and allenones has been developed. In the presence of a dipeptide phosphine catalyst 7, dihydrocoumarin-fused dihydropyrans were prepared in high yields and with excellent enantioselectivities. PMID:27173844

  14. N-Heterocyclic carbene-catalyzed [3 + 2] annulation of bromoenals with 3-aminooxindoles: highly enantioselective synthesis of spirocyclic oxindolo-γ-lactams.

    PubMed

    Chen, Kun-Quan; Li, Yao; Zhang, Chun-Lin; Sun, De-Qun; Ye, Song

    2016-02-14

    The chiral N-heterocyclic carbene-catalyzed [3 + 2] annulation of α-bromoenals and 3-aminooxindoles was developed, giving the corresponding spirocyclic oxindolo-γ-lactams in good yields with high diastereoselectivities and enantioselectivities. PMID:26755065

  15. A new and fast DLLME-CE method for the enantioselective analysis of zopiclone and its active metabolite after fungal biotransformation.

    PubMed

    de Albuquerque, Nayara Cristina Perez; de Gaitani, Cristiane Masetto; de Oliveira, Anderson Rodrigo Moraes

    2015-05-10

    Zopiclone (ZO) is a chiral drug that undergoes extensive metabolism to N-desmethylzopiclone (N-Des-ZO) and zopiclone-N-oxide (N-Ox-ZO). Pharmacological studies have shown (S)-N-Des-ZO metabolite presents anxiolytic activity and a patent for this metabolite was requested for anxiety treatment and related disorders. In this context, biotransformation employing fungi may be a promising strategy to obtain N-Des-ZO. To perform the biotransformation study in this work, an enantioselective method based on capillary electrophoresis (CE) and dispersive liquid-liquid microextraction (DLLME) was developed. CE analyses were carried out in sodium phosphate buffer (pH 2.5; 50mmolL(-1)) containing 0.5% (w/v) carboxymethyl-β-CD, at a constant voltage of +25kV. DLLME was conducted using 2mL of liquid culture medium pH 9.5. Chloroform (100μL) and methanol (300μL) were employed as extraction and disperser solvent, respectively. After CE and DLLME optimization, the analytical method was fully validated. The method was linear over a concentration range of 90-6000ngmL(-1) for each ZO enantiomer (r>0.999) and 50-1000ngmL(-1) for each N-Des-ZO enantiomer (r>0.998). Absolute recovery of 51 and 82% was achieved for N-Des-ZO and ZO, respectively. The accuracy and precision results agreed with the EMA (European Medicines Agency) guideline, and so did the stability study. Application of the developed method in a biotransformation study was conducted in order to investigate the ability of fungi, belonging to the genus Cunninghamella, in metabolizing ZO chiral drug. Fungi Cunninghamella elegans ATCC 10028B and Cunninghamella echinulata var elegans ATCC 8688A demonstrated to be able to enantioselectively biotransform ZO to its active metabolite, N-Des-ZO. Therefore, the proposed goals of this work, i.e. a fast DLLME-CE method and an outstanding strategy to obtain N-Des-ZO, were successfully attained. PMID:25778930

  16. Efficient alcoholysis of 5,6-dihydro-1,10-phenanthroline-5,6-epoxide with ytterbium(III) triflate and subsequent enantioselective transesterification with lipases

    PubMed Central

    Schoffers, Elke; Kohler, Lars

    2009-01-01

    New 5,6-dihydro-1,10-phenanthroline derivatives were prepared in high yield via ytterbium(III) triflate-catalyzed alcoholysis of the corresponding epoxide. Enzymatic transesterifications of racemic alkoxy alcohols afforded enantioselective separations with up to 99% ee. The lipase derived from Burkholderia cepacia (PSCI) was the most efficient, with E-values of up to 200. The steric effect of substituents in the 6-position on reaction time and enantioselectivities was assessed. PMID:20160975

  17. A cinchona alkaloid catalyzed enantioselective sulfa-Michael/aldol cascade reaction of isoindigos: construction of chiral bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters.

    PubMed

    Gui, Yong-Yuan; Yang, Jian; Qi, Liang-Wen; Wang, Xiao; Tian, Fang; Li, Xiao-Nian; Peng, Lin; Wang, Li-Xin

    2015-06-14

    A cinchona alkaloid catalyzed diastereoselective and enantioselective sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and isoindigos has been successfully developed to afford the highly congested bispirooxindole tetrahydrothiophenes with vicinal quaternary spirocenters in high yields (up to 91%), excellent diastereoselectivities (up to >20 : 1 dr), and good enantioselectivities (up to 98% ee). Some synthetic transformations of the reaction products were also studied. PMID:25974840

  18. A straightforward entry to chiral carbocyclic nucleoside analogues via the enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates.

    PubMed

    Xie, Ming-Sheng; Wang, Yong; Li, Jian-Ping; Du, Cong; Zhang, Yan-Yan; Hao, Er-Jun; Zhang, Yi-Ming; Qu, Gui-Rong; Guo, Hai-Ming

    2015-08-11

    A straightforward entry to chiral carbocyclic nucleoside analogues has been realized via the enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates to vinyl cyclopropanes for the first time. With Pd2(dba)3-L5 as the catalyst, carbocyclic purine, uracil, and thymine nucleoside analogues with quaternary stereocenters were obtained in excellent yields (up to 99% yield) and good enantioselectivities (up to 92% ee). PMID:26145719

  19. Enantioselective synthesis of 3-fluoro-3-allyl-oxindoles via phosphine-catalyzed asymmetric γ-addition of 3-fluoro-oxindoles to 2,3-butadienoates.

    PubMed

    Wang, Tianli; Hoon, Ding Long; Lu, Yixin

    2015-06-25

    The first phosphine-catalyzed enantioselective γ-addition of 3-fluoro-oxindoles to 2,3-butadienoates has been developed. A range of 3-fluoro-substituted oxindole substrates were employed, and oxindoles containing a 3-fluoro quaternary center were constructed in high yields and with excellent enantioselectivities. The γ-addition products could be converted readily to optically enriched 3-fluoro-3-allyl oxindole derivatives. PMID:26013076

  20. Chemo- and Enantioselective Addition and β-Hydrogen Transfer Reduction of Carbonyl Compounds with Diethylzinc Reagent in One Pot Catalyzed by a Single Chiral Organometallic Catalyst.

    PubMed

    Huang, Huayin; Zong, Hua; Bian, Guangling; Song, Ling

    2015-12-18

    Using a single chiral phosphoramide-Zn(II) complex as the catalyst, the asymmetric β-H transfer reduction of aromatic α-trifluoromethyl ketones and enantioselective addition of aromatic aldehydes with Et2Zn in one pot were successfully realized, affording the corresponding additive products of secondary alcohols in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee) and the reduction products of α-trifluoromethyl alcohols in good to excellent yields with up to 77% ee. PMID:26579727

  1. Altering the Enantioselectivity of Tyrosyl-tRNA Synthetase by Insertion of a Stereospecific Editing Domain.

    PubMed

    Richardson, Charles J; First, Eric A

    2016-03-15

    Translation of mRNAs by the ribosome is stereospecific, with only l-amino acids being incorporated into the nascent polypeptide chain. This stereospecificity results from the exclusion of d-amino acids at three steps during protein synthesis: (1) the aminoacylation of tRNA by aminoacyl-tRNA synthetases, (2) binding of aminoacyl-tRNAs to EF-Tu, and (3) recognition of aminoacyl-tRNAs by the ribosome. As a first step toward incorporating d-amino acids during protein synthesis, we have altered the enantioselectivity of tyrosyl-tRNA synthetase. This enzyme is unusual among aminoacyl-tRNA synthetases, as it can aminoacylate tRNA with d-tyrosine (albeit at a reduced rate compared to l-tyrosine). To change the enantioselectivity of tyrosyl-tRNA synthetase, we introduced the post-transfer editing domain from Pyrococcus horikoshii phenylalanyl-tRNA synthetase into the connective polypeptide 1 (CP1) domain of Geobacillus stearothermophilus tyrosyl-tRNA synthetase (henceforth designated TyrRS-FRSed). We show that the phenylalanyl-tRNA synthetase editing domain is stereospecific, hydrolyzing l-Tyr-tRNA(Tyr), but not d-Tyr-tRNA(Tyr). We further show that inserting the phenylalanyl-tRNA synthetase editing domain into the CP1 domain of tyrosyl-tRNA synthetase decreases the activity of the synthetic site in tyrosyl-tRNA synthetase. This decrease in activity is critical, as it prevents the rate of synthesis from overwhelming the ability of the editing domain to hydrolyze the l-Tyr-tRNA(Tyr) product. Overall, inserting the phenylalanyl-tRNA synthetase editing domain results in a 2-fold shift in the enantioselectivity of tyrosyl-tRNA synthetase toward the d-Tyr-tRNA(Tyr) product. When a 4-fold excess of d-tyrosine is used, approximately 40% of the tRNA(Tyr) is aminoacylated with d-tyrosine. PMID:26890980

  2. Ruthenium(salen)-catalyzed aerobic oxidative desymmetrization of meso-diols and its kinetics.

    PubMed

    Shimizu, Hideki; Onitsuka, Satoaki; Egami, Hiromichi; Katsuki, Tsutomu

    2005-04-20

    Chiral (nitrosyl)ruthenium(salen) complexes were found to be efficient catalysts for aerobic oxidative desymmetrization of meso-diols under photoirradiation to give optically active lactols. The scope of the applicability of this reaction ranges widely from acyclic diols to mono-cyclic diols, although fine ligand-tuning of the ruthenium(salen) complexes was required to attain high enantioselectivity (up to 93% ee). In particular, the nature of the apical ligand was found to affect not only enantioselectivity but also kinetics of the desymmetrization reaction. Spectroscopic analysis of the oxidation disclosed that irradiation of visible light is indispensable not only for dissociation of the nitrosyl ligand but also for single electron transfer from the alcohol-bound ruthenium ion to dioxygen. PMID:15826178

  3. Helical-Peptide-Catalyzed Enantioselective Michael Addition Reactions and Their Mechanistic Insights.

    PubMed

    Ueda, Atsushi; Umeno, Tomohiro; Doi, Mitsunobu; Akagawa, Kengo; Kudo, Kazuaki; Tanaka, Masakazu

    2016-08-01

    Helical peptide foldamer catalyzed Michael addition reactions of nitroalkane or dialkyl malonate to α,β-unsaturated ketones are reported along with the mechanistic considerations of the enantio-induction. A wide variety of α,β-unsaturated ketones, including β-aryl, β-alkyl enones, and cyclic enones, were found to be catalyzed by the helical peptide to give Michael adducts with high enantioselectivities (up to 99%). On the basis of X-ray crystallographic analysis and depsipeptide study, the amide protons, N(2)-H and N(3)-H, at the N terminus in the α-helical peptide catalyst were crucial for activating Michael donors, while the N-terminal primary amine activated Michael acceptors through the formation of iminium ion intermediates. PMID:27384597

  4. An aromatic ion platform for enantioselective Brønsted acid catalysis.

    PubMed

    Gheewala, Chirag D; Collins, Bridget E; Lambert, Tristan H

    2016-02-26

    Chiral acid catalysts are useful for the synthesis of enantioenriched small molecules, but the standard catalysts require laborious and expensive preparations. Here, we describe a chiral Brønsted acid prepared in one step from naturally occurring (-)-menthol and readily available 1,2,3,4,5-pentacarbomethoxycyclopentadiene. Aromatic stabilization serves as a key contributing factor to the potent acidity of the resulting compound, which is shown to catalyze both Mukaiyama-Mannich and oxocarbenium aldol reactions with high efficiency and enantioselectivity. Catalyst loadings as low as 0.01 mole percent and preparative scalability (25 grams) are demonstrated. Alternative amide catalysts are also shown to be promising platforms. In addition to proton catalysis, a chiral anion pathway is demonstrated to be viable with this catalyst system. PMID:26917768

  5. Organocatalytic Strategy for the Enantioselective Cycloaddition to Trisubstituted Nitroolefins to Create Spirocyclohexene-Oxetane Scaffolds.

    PubMed

    Monleón, Alicia; Glaus, Florian; Vergura, Stefania; Jørgensen, Karl Anker

    2016-02-12

    The first catalytic enantioselective cycloaddition reaction to α,β,β-trisubstituted nitroolefins is reported. For this purpose, nitroolefin oxetanes were employed in the reaction with 2,4-dienals promoted by trienamine catalysis. This methodology provides a facile and efficient strategy for the synthesis of highly functionalized chiral spirocyclohexene-oxetanes with two adjacent tetrasubstituted carbon atoms in high yields and excellent selectivities. This strategy also enabled access to chiral spirocyclohexene-cyclobutanes and -azetidines. Additionally, the obtained scaffolds can undergo diverse transformations leading to complex structures with up to four stereocenters, and we demonstrate that the nitro group, under nucleophilic conditions, can be applied for ring-opening of the oxetane. PMID:26757055

  6. Enantioselective syntheses and sensory properties of 2-methyl-tetrahydrofuran-3-thiol acetates.

    PubMed

    Dai, Yifeng; Shao, Junqiang; Yang, Shaoxiang; Sun, Baoguo; Liu, Yongguo; Ning, Ting; Tian, Hongyu

    2015-01-21

    The enantioselective synthesis of four stereoisomers of 2-methyl-tetrahydrofuran-3-thiol acetate was achieved. The two enantiomers of the important intermediate cis-2-methyl-3-hydroxy-tetrahydrofuran were obtained by Sharpless asymmetric dihydroxylation (AD), whereas the two enantiomers of trans-2-methyl-3-hydroxy-tetrahydrofuran were derived from the corresponding optically active cis-isomers by Mitsunobu reaction. Each stereoisomer of 2-methyl-3-hydroxy-tetrahydrofuran went through mesylation and nucleophilic substitution to afford the corresponding product with specific configuration. (2R,3S)- and (2R,3R)-2-methyl-tetrahydrofuran-3-thiol acetate were obtained in 80% ee, whereas the (2S,3R)- and (2S,3S)-isomers were in 62% ee. The odor properties of the synthesized four stereoisomers were evaluated by gas chromatography-olfactometry (GC-O), which revealed perceptible differences among stereoisomers both in odor features and in intensities. PMID:25560460

  7. Enantioselective Utilization of D-Amino Acids by Deep-Sea Microorganisms

    PubMed Central

    Kubota, Takaaki; Kobayashi, Tohru; Nunoura, Takuro; Maruyama, Fumito; Deguchi, Shigeru

    2016-01-01

    Microorganisms that utilize various D-amino acids (DAAs) were successfully isolated from deep-sea sediments. The isolates were phylogenetically assigned to Alphaproteobacteria, Gammmaproteobacteria, and Bacilli. Some of the isolates exhibited high enantioselective degradation activities to various DAAs. In particular, the Alphaproteobacteria Nautella sp. strain A04V exhibited robust growth in minimal medium supplemented with D-Val as a sole carbon and nitrogen source, whereas its growth was poor on minimal medium supplemented with L-Val instead of D-Val. Its growth was facilitated most when racemic mixtures of valine were used. In contrast, the Nautella strains isolated from shallow-sea grew only with L-Val. No significant differences were found among the strains in the genome sequences including genes possibly related to DAA metabolisms. PMID:27148200

  8. Highly Enantioselective Production of (R)-Halohydrins with Whole Cells of Rhodotorula rubra KCh 82 Culture

    PubMed Central

    Janeczko, Tomasz; Dymarska, Monika; Kostrzewa-Susłow, Edyta

    2014-01-01

    Biotransformation of ten α-haloacetophenones in the growing culture of the strain Rhodotorula rubra KCh 82 has been carried out. Nine of the substrates underwent an effective enantioselective reduction to the respective (R)-alcohols according to Prelog’s rule, with the exception of 2-chloro-1,2-diphenylethan-1-one that was not transformed by this strain. The expected reduction proceeded without dehalogenation, leading to the respective (R)-halohydrins in high yields. The use of this biocatalyst yielded (R)-2-bromo-1-phenyl-ethan-1-ol (enantiomeric excess (ee) = 97%) and its derivatives: 4'-Bromo- (ee = 99%); 4'-Chloro- (ee > 99%); 4'-Methoxy- (ee = 96%); 3'-Methoxy- (ee = 93%); 2'-Methoxy- (ee = 98%). There were also obtained and characterized 2,4'-dichloro-, 2,2',4'-trichloro- and 2-chloro-4'-fluoro-phenyetan-1-ol with >99% of enantiomeric excesses. PMID:25486054

  9. Enantioselective Synthesis of (−)-Maoecrystal V by Enantiodetermining C–H Functionalization

    PubMed Central

    2015-01-01

    The evolution of a program directed at the enantioselective total synthesis of maoecrystal V, a highly modified ent-kauranoid, is described. An early stage chiral auxiliary-directed asymmetric C–H functionalization for the construction of a key benzofuran intermediate enabled the first asymmetric synthesis of the natural enantiomer of maoecrystal V, confirming the assigned stereochemistry. A divergent course of the central intramolecular Diels–Alder reaction, which is dependent on the nature of the dienophile, initially led to the development of an unanticipated and previously unknown isomer of maoecrystal V, which we named maoecrystal ZG. In light of the reported selective and potent cytotoxic activity of maoecrystal V, the cytotoxic properties of maoecrystal ZG were also investigated. PMID:25409033

  10. Phormidolides B and C, cytotoxic agents from the sea: enantioselective synthesis of the macrocyclic core.

    PubMed

    Lorente, Adriana; Gil, Alejandro; Fernández, Rogelio; Cuevas, Carmen; Albericio, Fernando; Álvarez, Mercedes

    2015-01-01

    New cytotoxic polyketide macrolides named phormidolides B and C were isolated from a marine sponge of the Petrosiidae family collected off the coast of Pemba (Tanzania). The isolation, structure elucidation, and enantioselective synthesis of three diastereomers of the macrocyclic core is described herein. The described synthetic methodology started from 2-deoxy-D-ribose or 2-deoxy-L-ribose and afforded the desired macrocycles with high enantiomeric purity. The key step of the synthesis is the formation of the Z-trisubstituted double bond using a Julia-Kocienski olefination. The versatility of the synthetic methodology may provide access to other enantiopure macrocycles by making changes in the starting materials or chiral inductors. PMID:25359690

  11. Engineering chiral porous metal-organic frameworks for enantioselective adsorption and separation.

    PubMed

    Peng, Yongwu; Gong, Tengfei; Zhang, Kang; Lin, Xiaochao; Liu, Yan; Jiang, Jianwen; Cui, Yong

    2014-01-01

    The separation of racemic molecules is of substantial significance not only for basic science but also for technical applications, such as fine chemicals and drug development. Here we report two isostructural chiral metal-organic frameworks decorated with chiral dihydroxy or -methoxy auxiliares from enantiopure tetracarboxylate-bridging ligands of 1,1'-biphenol and a manganese carboxylate chain. The framework bearing dihydroxy groups functions as a solid-state host capable of adsorbing and separating mixtures of a range of chiral aromatic and aliphatic amines, with high enantioselectivity. The host material can be readily recycled and reused without any apparent loss of performance. The utility of the present adsorption separation is demonstrated in the large-scale resolution of racemic 1-phenylethylamine. Control experiments and molecular simulations suggest that the chiral recognition and separation are attributed to the different orientations and specific binding energies of the enantiomers in the microenvironment of the framework. PMID:25030529

  12. Engineering chiral porous metal-organic frameworks for enantioselective adsorption and separation

    NASA Astrophysics Data System (ADS)

    Peng, Yongwu; Gong, Tengfei; Zhang, Kang; Lin, Xiaochao; Liu, Yan; Jiang, Jianwen; Cui, Yong

    2014-07-01

    The separation of racemic molecules is of substantial significance not only for basic science but also for technical applications, such as fine chemicals and drug development. Here we report two isostructural chiral metal-organic frameworks decorated with chiral dihydroxy or -methoxy auxiliares from enantiopure tetracarboxylate-bridging ligands of 1,1‧-biphenol and a manganese carboxylate chain. The framework bearing dihydroxy groups functions as a solid-state host capable of adsorbing and separating mixtures of a range of chiral aromatic and aliphatic amines, with high enantioselectivity. The host material can be readily recycled and reused without any apparent loss of performance. The utility of the present adsorption separation is demonstrated in the large-scale resolution of racemic 1-phenylethylamine. Control experiments and molecular simulations suggest that the chiral recognition and separation are attributed to the different orientations and specific binding energies of the enantiomers in the microenvironment of the framework.

  13. Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel-Crafts alkylations.

    PubMed

    Pecchioli, Tommaso; Muthyala, Manoj Kumar; Haag, Rainer; Christmann, Mathias

    2015-01-01

    The first immobilization of a MacMillan's first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a-c was tested in the asymmetric Friedel-Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles. PMID:26150897

  14. Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

    PubMed Central

    Pecchioli, Tommaso; Muthyala, Manoj Kumar

    2015-01-01

    Summary The first immobilization of a MacMillan’s first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a–c was tested in the asymmetric Friedel–Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles. PMID:26150897

  15. Stereo and enantioselective separation and identification of synthetic pyrethroids, and photolytical isomerization analysis.

    PubMed

    Li, Z Y; Luo, X N; Li, Q L; Zhang, E Q; Zhao, J H; Zhang, W S

    2015-02-01

    Permethrin, cypermethrin and cyfluthrin are three important pyrethroids with similar structures and contain four, eight and eight stereoisomers, respectively. All the stereoisomers were completely resolved by a combination of achiral and chiral high-performance liquid chromatography with hexane/isopropanol as the mobile phase. The absolute configurations for the stereoisomers were also assigned on the basis of enantioselective resolution of permethrinic acid. For cypermethrin and cyfluthrin, although there is the only difference being one F atom substitution in cyfluthrin, the cis-I diastereomer exhibited a reversal of enantiomer order. Three specific stereoisomers were further isolated to investigate the photolysis and chiral stability of synthetic pyrethroids at the enantiomeric level. The results clearly revealed that significant isomerization occurred along with the photolysis process. The isomerization occurred at chiral 1-C position, 3-C position or both in the cyclopropyl ring, and the chiral 3-C exhibited a higher inversion tendency. PMID:25319199

  16. Side arm strategy for catalyst design: modifying bisoxazolines for remote control of enantioselection and related.

    PubMed

    Liao, Saihu; Sun, Xiu-Li; Tang, Yong

    2014-08-19

    In asymmetric catalysis, the remote control of enantioselection is usually difficult due to the long distance communication between the chiral center of the catalyst and the reactive site of the substrate. The development of efficient and highly enantioselective catalysts for such reactions is of great importance and highly desirable. The stereocontrol over an asymmetric reaction is a delicate process (ca. 3.0 kcal/mol difference in transition states can lead to >99/1 enantiomeric selectivity at room temperature), it therefore requires fine-tuning on the electronic nature of the central metal together with a precisely created cavity to accommodate the substrates and reagents. We envision that a solution is the design of new catalysts by finding an easy and efficient way to tune the electronic properties, the chiral space, and the shape of the catalytic site. Since an extra coordination group in the organometallic complex could not only alter the microenvironment around the metal center in a three-dimensional manner but also tune the electronic properties of the metal center, about 10 years ago, we introduced a side arm strategy for ligand/catalyst design. This Account describes our efforts toward this goal. Based on this side arm strategy, we have developed two series of ligands based on the bisoxazoline framework; namely, trisoxazoline (TOX) ligands and side armed bisoxazoline (SaBOX). The "side arms" are shown to play multiple roles in different cases, for example, as a ligating group, a steric group, or a directing group, which are dependent on the metal and the functionality at the side arm. Metal catalysts based on these ligands have proven to be highly efficient for a number of asymmetric transformations, including Friedel-Crafts reaction, Kinugasa reaction, Nazarov reaction, 1,2-Stevens rearrangement, Cannizzaro reaction, and cyclopropanation. In comparison with the parent BOX ligands, the metal catalysts based on these TOX and SaBOX ligands usually exhibit

  17. Developing novel organocatalyzed aldol reactions for the enantioselective synthesis of biologically active molecules

    PubMed Central

    Bhanushali, Mayur; Zhao, Cong-Gui

    2011-01-01

    Aldol reaction is one of the most important methods for the formation of carbon-carbon bonds. Because of its significance and usefulness, asymmetric versions of this reaction have been realized with different approaches in the past. Over the last decade, the area of organocatalysis has made significant progresses. As one of most studied reactions in organocatalyses, organocatalyzed aldol reaction has emerged as a powerful tool for the synthesis of a large number of useful products in optically enriched forms. In this review, we summarize our efforts on the development of novel organocatalyzed aldol reactions for the enantioselective synthesis of biological active molecules. Literatures closely related to our studies are also covered. PMID:21918584

  18. Enantioselective rhodium/ruthenium photoredox catalysis en route to chiral 1,2-aminoalcohols.

    PubMed

    Ma, Jiajia; Harms, Klaus; Meggers, Eric

    2016-08-01

    A rhodium-based chiral Lewis acid catalyst combined with [Ru(bpy)3](PF6)2 as a photoredox sensitizer allows for the visible-light-activated redox coupling of α-silylamines with 2-acyl imidazoles to afford, after desilylation, 1,2-amino-alcohols in yields of 69-88% and with high enantioselectivity (54-99% ee). The reaction is proposed to proceed via an electron exchange between the α-silylamine (electron donor) and the rhodium-chelated 2-acyl imidazole (electron acceptor), followed by a stereocontrolled radical-radical reaction. Substrate scope and control experiments reveal that the trimethylsilyl group plays a crucial role in this reductive umpolung of the carbonyl group. PMID:27462824

  19. Simple strategy for synthesis of optically active allylic alcohols and amines by using enantioselective organocatalysis

    PubMed Central

    Jiang, Hao; Holub, Nicole; Anker Jørgensen, Karl

    2010-01-01

    A simple organocatalytic one-pot protocol for the construction of optically active allylic alcohols and amines using readily available reactants and catalyst is presented. The described reaction is enabled by an enantioselective enone epoxidation/aziridination-Wharton-reaction sequence affording two highly privileged and synthetically important classes of compounds in an easy and benign way. The advantages of the described sequence include easy generation of stereogenic allylic centers, also including quaternary stereocenters, with excellent enantio- and diastereomeric-control and high product diversity. Furthermore, using monosubstituted enones as substrates, having moderate enantiomeric excess, the one-pot reaction sequence proceeds with an enantioenrichment of the products and high diastereoselectivity was achieved. PMID:20547884

  20. The First Enantioselective Organocatalytic Synthesis of 3-Spiro-α-Alkylidene-γ-Butyrolactone Oxindoles.

    PubMed

    Cerisoli, Lucia; Lombardo, Marco; Trombini, Claudio; Quintavalla, Arianna

    2016-03-01

    A new and flexible methodology catalyzed by bifunctional chiral thioureas has been developed to react β-nitro oxindoles 1 with aldehydes. This approach allowed us to achieve the first enantioselective organocatalytic synthesis of 3-spiro-α-alkylidene-γ-butyrolactone oxindoles 3. We examined the scope of the two starting materials and, varying the structure of the β-nitro oxindole 1, intriguing new products, derived from unexpected transformations, have been stereoselectively obtained. The aim of this study was to merge two potentially bioactive structural motifs: the spirooxindole substructure and the α-alkylidene-γ-butyrolactone moiety. A preliminary NMR study on the ability to reversibly trap 2-aminoethanethiol gave us promising results. PMID:26743560