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

2009; American Chemical Society; Volume: 74; Issue: 4 Linguagem: Inglês

10.1021/jo802495f

1520-6904

Haribabu Ankati, Dunming Zhu, Yan Yang, Edward R. Biehl, Ling Hua,

Chemical Synthesis and Analysis

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.