Chemoenzymatic Deracemization: One Enzyme, Both Enantiomers

Biocatalysis offers excellent selectivity and efficiency across a wide range of complex reactions; however, a major limitation is the lack of enantiomeric enzymes.^1,2 An effective biocatalyst for the stereoselective transformation of a single enantiomer provides no information on accessing the other. Unlike in chemocatalysis, where a ligand or catalyst with the opposite stereochemistry can be applied, accessing the opposite enantiomer with biocatalysis typically requires extensive re-screening followed by optimisation or directed evolution.

We present a novel strategy which enables access to either enantiomer using the same biocatalyst. Our approach utilizes concurrent chemoenzymatic deracemization, a powerful yet underdeveloped method in asymmetric synthesis, to convert racemic 1 into achiral 2 and back into 1 via non-microscopically, but formally, reverse pathways.^3,4 By controlling which step is stereoselective, we have developed cyclic and linear deracemization methodologies to achieve enantiodivergent access to a scope of seven chiral alcohols in excellent yields and enantiomeric excesses (ees).