Asymmetric synthesis of both antipodes of beta-hydroxy nitriles and beta-hydroxy carboxylic acids via enzymatic reduction or sequential reduction/hydrolysis.
Use of isolated carbonyl reductases in the reduction of aromatic beta-ketonitriles have completely eliminated the competing alpha-ethylation, which is often observed with whole cell biocatalysts. By choosing suitable recombinant carbonyl reductase, the reduction of beta-ketonitriles afforded (R)- or (S)-beta-hydroxy nitriles with excellent optical purity and yield. Subsequently, nitrilase-catalyzed hydrolysis of the obtained optically pure beta-hydroxy nitriles led to the corresponding beta-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 beta-hydroxy nitriles, lowering the cost and minimizing the environmental impact. This allows ready access to both antipodes of chiral beta-hydroxy nitriles and beta-hydroxy carboxylic acids of pharmaceutical importance with excellent optical purity.
Ankati
Haribabu
H
Department of Chemistry, Southern Methodist University, Dallas, Texas 75275, USA.
Zhu
Dunming
D
Yang
Yan
Y
Biehl
Edward R
ER
Hua
Ling
L
D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D000619:Aminohydrolases / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D020369:Bradyrhizobium / Q000201:enzymology*; D002175:Candida / Q000201:enzymology*; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D006868:Hydrolysis; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D002264:Carboxylic Acids; D009570:Nitriles; D000429:Alcohol Oxidoreductases; D000619:Aminohydrolases; C021867:nitrilase