A CHEMOENZYMATIC ELABORATION OF A QUARTERNARY CHIRAL CENTER - AN ALTERNATIVE APPROACH TO THE SIDE-CHAIN OF FURAQUINOCIN-D

A new approach to ethyl (2R, imethylsilyloxymethyl-3-hydroxy-2-methylb utanoate, a compound which is related to a synthetic intermediate of t he side chain of furaquinocin D, is described. The characteristic feat ure of this compound is a quarternary chiral center and an adjacent se condary alcohol, both of which are in a stereochemically defined state , and the setup of these functionalities was achieved by a combination of stereoselective chemical and enzymatic reactions. The reduction of ethyl 2-hydroxymethyl-2-methyl-3-oxobutanoate with excess NaBH4 affor ded (2R,3R*)-(+/-)-hydroxy ester with a high diastereomeric excess. A fter protecting the primary hydroxy group as TBDMS ether, the optical resolution was achieved by lipase-catalyzed hydrolysis of the correspo nding chloroacetate in a highly enantioselective manner. (C) 1998 Else vier Science Ltd. All rights reserved.