Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

Abstract

Chiral β-nitroalcohols are important building blocks in organic chemistry. The synthetic approach that is based on the enzyme-mediated reduction of α-nitroketones has been scarcely considered. In this work, the use of commercial alcohol dehydrogenases (ADHs) for the reduction of aromatic and aliphatic nitroketones is investigated. High conversions and enantioselectivities can be achieved with two specific ADHs, affording either the (S) or (R)-enantiomer of the corresponding nitroalcohols. The reaction conditions are carefully tuned to preserve the stability of the reduced product, and to avoid the hydrolytic degradation of the starting substrate. The further manipulation of the enantioenriched nitroalcohols into Boc-protected amminoalcohols is also described.