Biocatalytical Kinetic Resolution of Hydroxyalkanephosphonates

Abstract

Chiral hydroxyalkanephosphonic acids have received significant attention in recent years due to their potential biological activities and applications as chiral synthon in natural products synthesis. As found by us, a large number of ketoand diketo-phosphonates could be converted easily by baker’s yeast to chiral hydroxyalkanephosphonates in good yield and ee value with excellent regioand stereoselectivity depending on the nature of substituents located closed to carbonyl group. Unfortunately, 1-oxyalkanephosphonates resisted to such bioreductive system. In this article, a biocatalytical kinetic resolution of 1-hydroxyalkanephosphonates by Candida antartica lipase B (CALB) was reported. Our experimental data demonstrated that 1-hydroxyethanephosphonate underwent catalytic acylation with vinyl acetate as acyl donor in organic solvent using CALB as catalyst provided both (S)acylhydroxyethanephosphonate and (R)hydroxyethanephosphonate with 87–98% ee value. Under optimized conditions, (S)hydroxycomponent was exclusively acylated almost in quantitative yield.