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

Germain Obame (1) , Hélène Pellissier (2) , Nicolas Vanthuyne (2) , Jean-Bernard Bongui , Gérard Audran (3)

1 ICR - Institut de Chimie Radicalaire
2 ISM2 - Institut des Sciences Moléculaires de Marseille
3 STeRéO

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. (C) 2011 Elsevier Ltd. All rights reserved.

Domaines: Chimie

Germain Obame, Hélène Pellissier, Nicolas Vanthuyne, Jean-Bernard Bongui, Gérard Audran. Preparation of both enantiomers of a synthon for novel nucleoside analogs by enzymatic desymmetrization of a meso-diol with a methylene cyclopropane skeleton. Tetrahedron Letters, 2011, 52 (10), pp.1082--1085. ⟨10.1016/j.tetlet.2010.12.097⟩. ⟨hal-01460336⟩