321125-69-3

Upstream product

• 78533-73-0 3-phenylglutaronitrile 

Downstream Products

• 1078-21-3 (S)-Phenibut 
• 1078-21-3 (R)-Phenibut 
• 321125-73-9 ((R)-3-Cyano-2-phenyl-propyl)-carbamic acid methyl ester 

Relevant academic research and scientific papers

Inverting the Enantiopreference of Nitrilase-Catalyzed Desymmetric Hydrolysis of Prochiral Dinitriles by Reshaping the Binding Pocket with a Mirror-Image Strategy

A mirror-image strategy, that is, symmetry analysis of the substrate-binding pocket, was applied to identify two key amino acid residues W170 and V198 that possibly modulate the enantiopreference of a nitrilase from Synechocystis sp. PCC6803 towards 3-isobutyl glutaronitrile (1 a). Exchange of these two residues resulted in the enantiopreference inversion (S, 90 % ee to R, 47 % ee). By further reshaping the substrate-binding pocket via routine site-saturation and combinatorial mutagenesis, variant E8 with higher activity and stereoselectivity (99 % ee, R) was obtained. The mutant enzyme was applied in the preparation of optically pure (R)-3-isobutyl-4-cyanobutanoic acid ((R)-2 a) and showed similar stereopreference inversion towards a series of 3-substituted glutaronitriles. This study may offer a general strategy to switch the stereopreference of other nitrilases and other enzymes toward the desymmetric reactions of prochiral substrates with two identical reactive functional groups.

Microbial desymmetrization of 3-arylglutaronitriles, an unusual enhancement of enantioselectivity in the presence of additives

In the presence of an organic additive such as acetone or β-cyclodextrin or in a biphasic system of hexane and aqueous phosphate buffer, microbial desymmetrization of 3-arylglutaronitriles catalyzed by Rhodococcus sp. AJ270 cells proceeded regiospecifically and enantioselectively to produce S-(+)-3-aryl-4-cyanobutyric acids in high enantiomeric excess. Convenient chemoenzymatic syntheses of optically active R-(-)-4-amino-3-phenylbutyric acid and 4R-(-)-4-phenyltetrahydropyran-2-one are described. (C) 2000 Elsevier Science Ltd.

Improving the catalytic efficiency and stereoselectivity of a nitrilase from: Synechocystis sp. PCC6803 by semi-rational engineering en route to chiral γ-amino acids

Nitrilase-catalysed desymmetrization of 3-substituted glutaronitriles to optically active 3-substituted 4-cyanobutanoic acid offers an attractive approach to access chiral β-substituted γ-amino acids, an important moiety in pharmaceuticals. In this study,

Asymmetric cyclopropanation of conjugated cyanosulfones using a novel cupreine organocatalyst: Rapid access to δ3-amino acids

An organocatalytic asymmetric synthesis of a novel, highly functionalised cyclopropane system furnished with versatile substituents and containing a quaternary centre is described. The process utilises a new bifunctional catalyst based on the cinchona alkaloid framework and the products made using this catalyst were obtained as single diastereoisomers, with very high enantioselectivities (up to 96% ee). We have also demonstrated that these resulting cyclopropanes are very useful synthetic intermediates to interesting products, such as the difficult to access δ3-amino acids.

Biocatalytic desymmetrization of 3-substituted glutaronitriles by nitrilases. A convenient chemoenzymatic access to optically active (S)-Pregabalin and (R)-Baclofen

Desymmetrization of prochiral 3-substituted glutaronitriles offers a new approach to access (S)-Pregabalin and (R)-Baclofen. A number of nitrilases from diverse sources were screened with 3-isobutylglutaronitriles (1a) or 3-(4′-chlorophenyl)glutaronitriles (1b) as the substrate. Some nitrilases were found to catalyze the desymmetric hydrolysis of 1a and 1b to form optically active 3-(cyanomethyl)-5-methylhexanoic acid (2a) and 3-(4′-chlorophenyl) -4-cyanobutanoic acid (2b) with high enantiomeric excesse (ee), respectively. This cannot be achieved using traditional chemical hydrolysis. Among them, AtNIT3 generated (R)-2b, whereas BjNIT6402 and HsNIT produced the opposite (S)-enantiomer with high conversions and ee values. Not only the nitrilases showed different activities and stereoselectivities toward these 3-substituted glutaronitriles, the 3-substituent of the substrates also exerted great effect on the enzyme activity and stereoselectivity. (S)-2a and (S)-2b were prepared with high yields and ee values using BjNIT6402 and HsNIT as the biocatalysts, respectively. A straightforward Curtius rearrangement of (S)-2a and (S)-2b, followed by the acidic hydrolysis, afforded (S)-Pregabalin and (R)-Baclofen. This offers a new platform methodology for the synthesis of optically active β-substituted γ-amino acids of pharmaceutical importance.

Enzymatic desymmetrization of 3-alkyl- and 3-arylglutaronitriles, a simple and convenient approach to optically active 4-amino-3-phenylbutanoic acids

The enantioselective hydrolysis of 3-alkyl- and 3-arylglutaronitriles catalyzed by Rhodococcus sp. AJ270 cells, afforded the corresponding (S)-3-substituted 4-cyanobutanoic acids with low to moderate enantiomeric purities. Additives such as acetone were found to significantly enhance the enantioselectivity of the desymmetrization, giving enantiomeric excesses of up to 95%. The synthetic potential of the homochiral product was also demonstrated by the preparation of optically active (R)- and (S)-4-amino-3-phenylbutanoic acids.