COMBINATORIAL APPROACH TOWARDS SYNTHESIS OF 2',3'-DIDEOXYNUCLEOSIDES AND ENZYME-CATALYZED SELECTIVE HYDROLYSIS OF DIETHYL ACETAMIDOMALONATEAND AMIDES OF POLYACETOXY AROMATIC CARBOXYLIC-ACID

Seventeen novel 3'-alkylthio-2',3'-dideoxynucleosides have been synthe sised by Michael-type addition of alkylthiols to an alpha,beta-unsatur ated hexose aldehyde, followed by acetylation, nucleoside coupling and deprotection. Based on these results, a general scheme for combinator ial synthesis of libraries of 3'-substituted 2',3'-dideoxynucleosides has been proposed. Porcine pancreatic lipase (PPL) has been found to h ydrolyse the amides of polyacetoxyaromatic carboxylic acids in a highl y chemoselective fashion. The enzyme exclusively hydrolyses the ester group over the amide group. Hydrolysis of diethyl acetamidomalonate in phosphate buffer in the presence of alpha-chymotrypsin proceeds enant ioselectively affording the (+)-monoacid.