Combinatorial approach towards synthesis of 2',3'-dideoxynucleosides and enzyme-catalysed selective hydrolysis of diethyl acetamidomalonate and amides of polyacetoxy aromatic carboxylic acid

Abstract

Seventeen noveI 3’-alkylthio-2’,3’-dideoxynucleosides have been synthesised by Michael-type addition of alkylthiols to an ,α,β-unsaturated hexose aldehyde, followed by acetylation, nucleoside coupling and deprotection. Based on these results, a general scheme for combinatorial synthesis of libraries of 3’-substituted 2’,3’-dideoxynucleosides has been proposed. Porcine pancreatic lipase (PPL) has been found to hydrolyse the amides of polyacetoxyaromatic carboxylic acids in a highly chemoselective fashion. The enzyme exclusively hydrolyses the ester group over the amide group. Hydrolysis of diethyl acetamidomalonate in phosphate buffer in the presence of α-chymotrypsin proceeds enantioselectively affording the (+)-monoacid.