REGIOSELECTIVE ENZYMATIC ACYLATION AS A TOOL FOR PRODUCING SOLUTION-PHASE COMBINATORIAL LIBRARIES

A simple combinatorial strategy for sequential regioselective enzymati c acylation of multifunctional lead compounds has been developed and d emonstrated using a polyhydroxylated flavonoid, bergenin, as a model. The approach is based on the ability of different enzymes to regiosele ctively acylate different sites on a lead molecule without affecting o ther similar functional groups. In sharp contrast to enzymatic acylati on, conventional chemical acylation methods showed almost complete lac k of regioselectivity. The enzymatic strategy was applied successfully to produce a solution phase combinatorial library of 167 distinct sel ectively acylated derivatives of bergenin on a robotic workstation in a 96-well plate format. General applicability of the automated combina torial biocatalysis strategy is discussed. (C) 1998 Published by Elsev ier Science Ltd. All rights reserved.