Asymmetric Synthesis of Both Antipodes of β-Hydroxy Nitriles and β-Hydroxy Carboxylic Acids via Enzymatic Reduction or Sequential Reduction/Hydrolysis

• Published in: Journal of organic chemistry 2009-02, Vol.74 (4), p.1658-1662
• Main Authors: Ankati, Haribabu, Zhu, Dunming, Yang, Yan, Biehl, Edward R, Hua, Ling
• Format: Article
• Language: English
• Subjects: Alcohol Oxidoreductases - chemistry; Alcohol Oxidoreductases - metabolism; Aliphatic compounds; Aminohydrolases - chemistry; Aminohydrolases - metabolism; Biocatalysis; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Bradyrhizobium - enzymology; Candida - enzymology; Carboxylic Acids - chemical synthesis; Carboxylic Acids - chemistry; Chemistry; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Hydrolysis; Methods. Procedures. Technologies; Nitriles - chemical synthesis; Nitriles - chemistry; Organic chemistry; Oxidation-Reduction; Preparations and properties; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo802495f

Use of isolated carbonyl reductases in the reduction of aromatic β-ketonitriles have completely eliminated the competing α-ethylation, which is often observed with whole cell biocatalysts. By choosing suitable recombinant carbonyl reductase, the reduction of β-ketonitriles afforded (R)- or (S)-β-hydroxy nitriles with excellent optical purity and yield. Subsequently, nitrilase-catalyzed hydrolysis of the obtained optically pure β-hydroxy nitriles led to the corresponding β-hydroxy carboxylic acids in high yields. More importantly, the sequential enzymatic reduction and hydrolysis could be carried out in “two-step-one-pot” fashion without the isolation of intermediates β-hydroxy nitriles, lowering the cost and minimizing the environmental impact. This allows ready access to both antipodes of chiral β-hydroxy nitriles and β-hydroxy carboxylic acids of pharmaceutical importance with excellent optical purity.