Chemoenzymatic syntheses of enantiomerically pure hydroxy amino acids

Abstract

Hydroxy amino acids constitute essential partial structures of many biologically important compounds. While there are several ways of controlling the stereochemistry of condensation- or ring opening reactions leading to erythro- or threo- products of high diastereomeric purity there is no generally applicable method of separation of these racemates into their respective optical antipodes. Here we describe the enantiomeric resolution of easily obtainable precursors, namely azido hydroxy derivatives. The resolutions are accomplished by hydrolysis of the respective O-acyl derivatives of the hydroxy azido carboxylic acid esters with the aid of commercially available lipases, mainly from Candida cylindracea and Pseudomonas fluorescens. The rates of conversion and the enantiomeric purities attainable are demonstrated with all four diastereo-mers of azido hydroxy 3-phenylpropionic acid (precursors of phenylserine and phenyl-iso-serine). Details on the dependence of the stereospecifity of the hydrolysis on the kind of the ester used as well as on the regiosisomer employed are given. The simplicity of the method easily allows for scale up of the preparative procedure and thus shows promise for the extension to other systems of biological interest.