Preparation of both enantiomers of a synthon for novel nucleoside analogs by enzymatic desymmetrization of a meso-diol with a methylene cyclopropane skeleton

Abstract

The enzymatic desymmetrization of methylenecyclopropane diol or its corresponding diacetate derivative, generated from a [2+1] cycloaddition between dioxepin and methylchlorocarbene, is described. After screening five commercial lipases, the two enantiomers of acetic acid 2-hydroxymethyl-3-methylene-cyclopropylmethyl ester are obtained in high yields and excellent enantioselectivities by using PFL or LPP in organic solvent. The stereostructure of the desymmetrization products was established by X-ray analysis. We also reported a new example with this non racemic chiral building block where the sign of optical rotation is dramatically solvent dependent and inverted. Using these enantiopure building blocks, a synthesis of novel nucleoside analogs is also presented.