Synthesis of ( R)-β-nitro alcohols catalyzed by R-selective hydroxynitrile lyase from Arabidopsis thaliana in the aqueous–organic biphasic system

Abstract

Both enantiomers of β-nitro alcohols are versatile chiral building blocks. However, their synthesis using enzymes as catalysts has received little attention, with the exception of ( S)-β-nitro alcohols produced in a reaction catalyzed by an S-selective hydroxynitrile lyase (HNL) from Hevea brasiliensis ( HbHNL). An R-selective HNL containing an α/β-hydrolase fold from the noncyanogenic plant Arabidopsis thaliana ( AtHNL) accepts nitromethane (MeNO 2) as a donor in a reaction with aromatic aldehydes to yield ( R)-β-nitro alcohols (Henry reaction; nitro aldol reaction). This reaction proceeded in an aqueous–organic biphasic system. The organic solvent giving the highest enantioselectivity was n-butyl acetate (AcOBu) with an optimum aqueous phase content of 50% (v/v). This is the first example of the R-HNL-catalyzed synthesis of ( R)-β-nitro alcohols.