A Single Enzyme in Enantiocomplementary Synthesis of β-Nitroalcohols: Bidirectional Catalysis by Hydroxynitrile Lyase

Abstract

A single enzyme, Baliospermum montanum hydroxynitrile lyase (BmHNL), without alteration, enabled bidirectional catalysis in enantiocomplementary synthesis of chiral β-nitroalcohols. BmHNL catalyzed promiscuous Henry (24 examples) and retro-Henry reaction (22 examples) provided up to >99 % and 50 % conversion to (S)- and (R)-β-nitroalcohols respectively, while both cases displayed up to >99 % ee. The broad substrate scope and high stereoselectivity of BmHNL represents its synthetic applications in sustainable production of diverse chiral β-nitroalcohols. Kinetic parameters of BmHNL was determined for Henry and retro-Henry reaction, which reveals poor catalytic efficiency for both the promiscuous transformations, however, the former has better efficiency than the latter. Practical applicability of the biocatalyst and transformation was illustrated by preparative scale synthesis of chiral intermediates of (S)-Tembamide, and (S)-Micanozole.

Keywords: Henry reaction; asymmetric synthesis; biocatalysis; hydroxynitrile lyase; retro-Henry reaction.