Optical Rotatory Dispersion of Rotundifolone

Microbial (enzymatic) hydrolysis of (±)-O-acetyl allethrolone gave (?)-(R)-allethrolone with (+)-(S)-O-acetyl allethrolone. And microbial hydrolysis of (±)-cis and trans-2-allylcyclopentyl acetates gave the low optically active cis and trans-2-allylcyclopentanols with the acetates of their antipodes. Also, the acetates of (±)-primary alcohols with cyclopropane and cyclohexene rings: (±)-chrysanthemyl alcohol, α-cyclogeraniol, were hydrolyzed by microorganisms to give the optically active alcohols in low optical purities Further, synthesis and microbial resolution of racemic hydroxy-trimethylcyclohexanones, useful intermediate for synthesis of compounds related to carotenoids, were tried.     

Carbon Anionic Chiral Initiators for Asymmetric Anionic Polymerization of Achiral Isocyanates

Novel optically active carbon anionic initiators bearing a chiral oxazole substituent on fluorene ring, (S)‐1‐(9H‐fluoren‐2‐yl)‐4‐isopropyl‐4, 5‐dihydrooxazole lithium ((S)‐1‐FIDD‐Li) and (S)‐2‐(9H‐fluoren‐2‐yl)‐4‐isopropyl‐4, 5‐dihydrooxazole lithium ((S)‐2‐FIDD‐Li), were synthesized. Anionic polymerizations of achiral polyisocyanates with the chiral initiators were investigated and optical rotation of the obtained polymers were attributed to asymmetric induction of the chiral initiators. The crowded substituent of initiator ((S)‐2‐FIDD‐Li) seems to reduce the polymerizability of isocyanates and yet enhances the chiral induced ability in polymerization. Chirality 27:449–453, 2015. © 2015 Wiley Periodicals, Inc.     

Baker’s yeast mediated asymmetric reduction of cinnamaldehyde derivatives

The enantioselective reduction of cinnamaldehyde derivatives is an attractive strategy to prepare various optically active multifunctional molecules that can be used as chiral building blocks for the synthesis of some HIV-protease inhibitors. The asymmetric reduction with pH adjusted to 5.5 of α-substituted-cinnamaldehydes (Br, N₃) mediated by baker’s yeast (Saccharomyces cerevisiae) yielded α-substituted-3-phenyl-1-propanol in excellent enantiomeric excesses and yields.     

Synthesis of optically pure 1,2-epoxypropane by microbial asymmetric reduction of chloroacetone

A number of bacteria and yeast was screened for asymmetric reduction of prochiral chloroacetone into chiral 1-chloro-2-propanol, which is chemically convertible into chiral 1,2-epoxypropane. In this way Rhodotorula glutinis produced optically pure S-1,2-epoxypropane with 98% enantiomeric excess and in a relatively high final concentration. The enzyme that catalysed the asymmetric reduction was an NAD(P)H-dependent alcohol dehydrogenase. Reduction of racemic 3-chloro-2-butanone resulted in mixtures of cis and trans-2,3-epoxybutane, indicating that no enantioselective reduction of this haloketone occurred. Correspondence to: C. A. G. M. Weijers     

Highly selective anti-Prelog synthesis of optically active aryl alcohols by recombinant Escherichia coli expressing stereospecific alcohol dehydrogenase

Biocatalytic asymmetric synthesis has been widely used for preparation of optically active chiral alcohols as the important intermediates and precursors of active pharmaceutical ingredients. However, the available whole-cell system involving anti-Prelog specific alcohol dehydrogenase is yet limited. A recombinant Escherichia coli system expressing anti-Prelog stereospecific alcohol dehydrogenase from Candida parapsilosis was established as a whole-cell system for catalyzing asymmetric reduction of aryl ketones to anti-Prelog configured alcohols. Using 2-hydroxyacetophenone as the substrate, reaction factors including pH, cell status, and substrate concentration had obvious impacts on the outcome of whole-cell biocatalysis, and xylose was found to be an available auxiliary substrate for intracellular cofactor regeneration, by which (S)-1-phenyl-1,2-ethanediol was achieved with an optical purity of 97%e.e. and yield of 89% under the substrate concentration of 5 g/L. Additionally, the feasibility of the recombinant cells toward different aryl ketones was investigated, and most of the corresponding chiral alcohol products were obtained with an optical purity over 95%e.e. Therefore, the whole-cell system involving recombinant stereospecific alcohol dehydrogenase was constructed as an efficient biocatalyst for highly enantioselective anti-Prelog synthesis of optically active aryl alcohols and would be promising in the pharmaceutical industry.     

Synthesis and absolute configuration of the stereoisomers of [2-(1-diethylaminopropyl)] 1-hydroxy-1,1′-bicyclohexyl-2-carboxylate,a muscarinic antagonist

The compound [2-(1-diethylaminopropyl)] 1-hydroxy-1,1′-bicyclohexyl-2-carboxylate 1 is a muscarinic antagonist characterized by the presence of three chiral atoms and eight possible stereoisomers. The binding affinities to the five cloned m₁–m₅ muscarinic receptors of the stereoisomers of 1 were previously investigated and proved to be related to the chirality of the molecules. The eight isomers are prepared through the synthesis of their racemates followed by chemical resolution as (+) and (−) tartrate or (+) and (−) dibenzoyltartrate salts. The isomers with cis-configuration of OH and COOH substituents of the cyclohexane are also obtained by coupling optically active (1S, 2S) or (1R,2R)-1-hydroxy-[1,1′-bicyclohexyl]-2-carboxylic acid with (S)- or (R)-1-diethylamino-2-propanol. Chiral GC and HPLC methods are used to determine their optical purity. The absolute configurations of the four cis- and four trans-isomers are established by stereospecific synthesis and X-ray crystallographic data. Chirality 9:713–721, 1997. © 1997 Wiley-Liss, Inc.     

Asymmetric Synthesis and Sensory Evaluation of Sedanenolide

The synthesis and sensory evaluation of enantiomeric sets of sedanenolide (1) and 3-butylphthalide (3) are described. The asymmetric synthesis was achieved via the intramolecular Diels-Alder reaction of chiral propargylester (5) which was prepared from optically active propargyl alcohol (4) and 2,4-pentadienoic acid. The sensory evaluation of these enantiomers revealed that there were distinct differences between their aroma character and odor threshold.     

Optically-Active compounds via biocatalytic methods

Different approaches to improve the enantioselectivity of biocatalytic systems are presented. These methodologies have been successfully applied to the preparation of optically active dihydropyridine, calcium antagonists, and cis-3-hydroxy-6-acetoxy-cyclohex-1-ene, a valuable chiral building block for natural products synthesis. The phenomenon of enantioselective inhibition is described and several new heterocyclic amines have been shown to be effective enantioselective inhibitors in the Candida lipase system.     

Enantiospecific enzymatic preparation of (2S,3S)-3-alkylaspartic acids of current interest in the synthesis of stereoregular poly[β-(2S,3S)-3-alkylmalic acids] as new optically active functional polyesters

(2S,3S)-3-methyl- and 3-isopropylaspartic acids were synthesized by bioconversion of the corresponding alkylfumarates (mesaconate and 3-isopropylfumarate) using β-methylaspartase from cell-free extracts of Clostridium tetanomorphum. Optically pure (2S,3S)-3-alkylaspartic acids were transformed in several steps to benzyl (3S,4R)-3-alkylmalolactonates without any racemization of the two chiral centers. These optically active α,β-substituted-β-lactones were polymerized by anionic ring opening polymerization yielding optically active semi-crystalline polyesters. ¹³C NMR analysis of poly[benzyl β-3-isopropylmalate] in CDCl₃ has shown that only the iso-type stereosequence is present in the polymer, indicating that the macromolecular chain is constituted by the only units of benzyl β-(2S,3S)-3-isopropylmalate monomer. The polymerization reaction was done without any racemization of the two stereogenic centers as in the case of benzyl (3S,4R)-3-methylmalolactonate. © 1996 Wiley-Liss, Inc.     

Synthesis of racemic and optically active glycidic ethers,precursors of liquid crystalline polyethers

A series of racemic and optically active oxiranes, bearing mesogenic groups, precursors of liquid crystalline polyethers, has been synthesized from epichlorohydrin or glycidol. The enantiomeric excess of the optically active oxiranes has been determined by chiral stationary phase HPLC. Compounds bearing 4-cyanobiphenyl mesogenic group exhibit monotropic liquid crystalline behavior. A transfer of chirality to the mesophase has been observed for the optically active oxiranes, which present a cholesteric phase. Chirality 10:779–785, 1998. © 1998 Wiley-Liss, Inc.     

Chiral P-monodentate phosphoramidite and phosphite ligands for the enantioselective Pd-catalyzed allylic alkylation

The improved synthesis of the chiral phosphoramidite Ia, based on a biphenol backbone and bearing chiral bis(1-phenylethyl)amine group on the phosphorus atom, is described together with its Pd(II) complex. The chiral complex cis-PdCl₂L₂ (L = Ia) has been characterized by X-ray crystal structure analysis and spectroscopic data. The series of the chiral P-monodentate phosphoramidite and phosphite ligands was tested in Pd-catalyzed enantioselective allylic substitution of different substrates. In the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenylallyl acetate with dimethylmalonate, up to 79% ee was achieved with [Pd₂(dba)₃] × CHCl₃ as precatalyst.     

Highly Enantioselective Production of Chiral Secondary Alcohols with Candida zeylanoides as a New Whole Cell Biocatalyst

The increasing demand for biocatalysts in synthesizing enantiomerically pure chiral alcohols results from the outstanding characteristics of biocatalysts in reaction, economic, and ecological issues. Herein, fifteen yeast strains belonging to three food originated yeast species Candida zeylanoides, Pichia fermentans, and Saccharomyces uvarum were tested for their capability for asymmetric reduction of acetophenone to 1‐phenylethanol as biocatalysts. Of these strains, C. zeylanoides P1 showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high yields. The preparative scale asymmetric bioreduction of 4‐nitroacetophenone ( 1m ) by C. zeylanoides P1 gave (S)‐1‐(4‐nitrophenyl)ethanol ( 2m ) with 89% yield and > 99% enantiomeric excess. Compound 2m has been obtained in an enantiomerically pure and inexpensive form. Additionally, these results indicate that C. zeylanoides P1 is a promising biocatalyst for the synthesis of chiral alcohols in industry.     

Resolution of RS-abscisic acid and the separation of abscisic acid metabolites from plant tissue by high-performance liquid chromatography

Attempts to resolve the enantiomers of racemic abscisic acid (ABA) by high-performance liquid chromatograpy on a chiral stationary-phase column were unsuccessful. However, reduction of RS-methyl ABA (RS-Me-ABA) with sodium borohydride generates a new chiral centre and one of the two isomeric products, the RS-Me-1′,4′-cis-diol of ABA, was separated into its enantiomers by high-performance liquid chromatography on an optically active Pirkle column.High-performance liquid chromatography on a μBondapak C₁₈ column separated the metabolites and conjugates of [2-¹⁴C]ABA fed to tomato shoots. The resolution method was used to measure the relative proportions of R and S enantiomers in the free acid liberated from conjugates of ABA.     

Synthesis,HPLC Enantioresolution,and X‐ray Analysis of a New Series of C5‐methyl Pyridazines as N‐Formyl Peptide Receptor (FPR) Agonists

The synthesis of three racemates and the corresponding non‐chiral analogues of a C5‐methyl pyridazine series is described here, as well as the isolation of pure enantiomers and their absolute configuration assignment. In order to obtain optically active compounds, direct chromatographic methods of separation by HPLC‐UV were investigated using four chiral stationary phases (CSPs: Lux Amylose‐2, Lux Cellulose‐1, Lux Cellulose‐2 and Lux Cellulose‐3). The best resolution was achieved using amylose tris(5‐chloro‐2‐methylphenylcarbamate) (Lux Amylose‐2), and single enantiomers were isolated on a semipreparative scale with high enantiomeric excess, suitable for biological assays. The absolute configuration of optically active compounds was unequivocally established by X‐ray crystallographic analysis and comparative chiral HPLC‐UV profile. All compounds of the series were tested for formyl peptide receptor (FPR) agonist activity, and four were found to be active, with EC₅₀ values in the micromolar range. Chirality 25:400–408, 2013. © 2013 Wiley Periodicals, Inc.     

Synthesis and enantiomeric purity determination of chiral 3-benzylglycidol,a key synthon for hiv protease inhibitors

The detailed synthesis of (2R,3R)-3-benzylglycidol by the Sharpless asymmetric epoxidation route is described. The enantiomeric purity determination of this compound is complicated by the presence of small quantities of the diastereometric (2R,3S)-3-benzylglycidol from the asymmetric epoxidation of the cis-allylic alcohol, and the unreacted allylic alcohols that are not removed in the product isolation steps. We have developed a direct chiral HPLC method that can resolve all these components for the precise determination of enantiomeric excesses of chiral 3-benzylglycidols. © 1994 Wiley-Liss, Inc.     

Stereoselective Synthesis of (2R, 3S)-2-Benzyl-2-hydroxy-3- (3,4-methylenedioxybenzyl)-γ-butyrolactone from L-(+)-Arabinose

As a model experiment for the stereoselective synthesis of optically active cis-α,β-dibenzyl-α-hydroxy-γ-butyrolactone, (2R, 3S)-2-benzyl-2-hydroxy-3-(3,4-methylenedioxybenzyl)-γ-butyrolactone (3) was stereoselectively synthesized from L-(+)-arabinose.     

Asymmetric Trans-esterification of meso-2,5-Dibromoadipate and Synthesis of Optically Active cis-2,5-Disubstituted Pyrrolidines

Asymmetric trans-esterification of meso-2,5-dibromoadipate to (–)-benzyl methyl 2,5-dibromoadipate by lipase with subsequent chemical reactions afforded optically active cis-2,5-disubstituted pyrrolidines. An equivalent asymmetric transformation was performed by selectively hydrolyzing a cis-2,5-disubstituted pyrrolidine having a chiral N-substituent.     

Biomimetic asymmetric oxidative coupling of phenols

This paper describes the first examples of asymmetric induction in the oxidative coupling of phenols using chiral oxidants. When chiral cupric-amine complexes were used as oxidants, low asymmetric induction was achieved in the coupling of naphthols. The formation of optically active d-dehydrogriseofulvin and l-Licarin A using the cupric-l-a-phenylethylamine complex perhaps mimics the action of copper-containing enzymes known to catalyze phenol coupling.     

Debaryomyces hansenii as a new biocatalyst in the asymmetric reduction of substituted acetophenones

Chiral secondary alcohols are convenient mediator for the synthesis of biologically active compounds and natural products. In this study fifteen yeast strains belonging to three food originated yeast species Debaryomyces hansenii, Saccharomyces cerevisiae and Hanseniaspora guilliermondii were tested for their capability for the asymmetric reduction of acetophenone to 1-phenylethanol as biocatalyst microorganisms. Of these strains, Debaryomyces hansenii P1 strain showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to the corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high conversion rates. This is the first report on the enantioselective reduction of acetophenone by D. hansenii P1 from past?rma, a fermented Turkish meat product. The preparative scale asymmetric bio reduction of 3-methoxy acetophenone 1g by D. hansenii P1 gave (R)-1-(3-methoxyphenyl) ethanol 2g 82% yield, and >99% enantiomeric excess. Compound 2g can be used for the synthesis of (+)-NPS-R-568 [3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenly) ethyl] propan-1-amine] which have a great potential for the treatment of primary and secondary hyper-parathyroidism. In addition, D. hansenii P1 successfully reduced acetophenone derivatives. This study showed that this yeast can be used industrially to produce enantiomerically pure chiral secondary alcohols, which can be easily converted to different functional groups.     

Axial chirality in biaryl N,N-dialkylaminopyridine derivatives bearing an internal carboxy group

Axial chirality in N,N-dimethylaminopyridines as well as N,N-dipropylaminopyridines bearing an internal carboxy group were evaluated based on their racemization barriers and circular dichroism spectra. The half-life of racemization of N,N-dipropylaminopyridine derivative 2 was estimated to be 19.7 days at 20°C. Its enantiomers isolated as optically active forms showed positive-negative and negative-positive Cotton effects for (+)- 2 and (−)- 2 , respectively, from 310 to 210 nm. Furthermore, (−)- 2 was applied as a chiral nucleophilic catalyst and exhibited asymmetric induction in acylative kinetic resolution of 1-(1-naphthyl)ethane-1-ol.