Lipase-catalyzed enantio- and regioselective transformation of 3-epi-shikimic acid derivatives as the key step for the entry of polyoxygenated carbacycles

Abstract

Candida antarctica lipase B (Novozym 435)-catalyzed transesterification on methyl (±)-3,4-di-O-acetyl-5-O-(tert-butyldimethyl)silyl-3-epi-shikimate worked highly regio- and enantioselective manner. Only (3R,4S,5S)-isomer reacted with an E value over 500, exclusively on C-3 acetate. The regio- and enantioselectivity were greatly affected by the substitution pattern on the hydroxy groups. Towards polyoxygenated carbacycles, the above-mentioned highly selective transformation enabled the subsequent stereoselective inversion and dihydroxylation, to give methyl (3S,4R,5S)-3,4,5-triacetoxy-1-cyclohexenecarboxylate [antipode of naturally occurring methyl (−)-3,4,5-tri-O-acetylshikimate], and methyl (1R,2S,3S,4R,5R)-3,4-diacetoxy-5-(tert-butyldimethyl)silyloxy-1,2-dihydroxy-cyclohexanecarboxylate.