Chemoenzymatic synthesis of enantiomerically enriched α-chiral 3-oxy-propionaldehydes by lipase-catalyzed kinetic resolution and desymmetrization

Abstract

Enantiomerically enriched phenylalanine- and leucine aldehyde analogues have been prepared by lipase catalyzed desymmetrization or kinetic resolution of 1,3-propanediol derivatives as key steps. Observations of unusual enantioselectivity were made, and most notably, Candida antarctica lipase B showed an opposite enantiopreference from other lipases, which was exploited in the synthesis. A thorough evaluation of chemoenzymatic routes to both enantiomers of the target α-chiral 3-oxy-propionaldehydes resulted in simple, inexpensive, and efficient procedures that provide the products in up to 92% enantiomeric excess and 55% total yield in five steps from easily accessible starting materials.