Stereoselective synthesis of deoxycarbaheptopyranose derivatives: 5a-carba-6-deoxy-alpha-DL-galacto-heptopyranose and 5a-carba-6-deoxy-alpha-DL-gulo-heptopyranose

Abstract

Two new deoxycarbaheptopyranoses, 5a-carba-6-deoxy-alpha-DL-galacto-heptopyranose and 5a-carba-6-deoxy-alpha-DL-gulo-heptopyranose were prepared starting from cyclohexa-1,4-diene. The addition of dichloroketene to cyclohexa-1,4-diene followed by the subsequent reductive elimination and Baeyer-Villiger oxidation in turn led to the formation of a bicyclic lactone. Reduction of the lactone moiety followed by acetylation gave a diacetate with cis-configuration. The introduction of additional acetate functionality into the molecule was achieved by singlet oxygen ene-reaction. The formed hydroperoxide was reduced and then acetylated. The triacetate was further functionalized either by direct cis-hydroxylation using OsO4 or by epoxidation followed by a ring-opening reaction to give the title heptopyranose derivatives. One of the synthesized molecules, galacto-heptopyranose exhibited enzyme specific inhibition against alpha-glycosidase. On the other hand, they did not show any inhibition for alpha-amylase. However, both compounds, gulo-heptopyranose and galacto-heptopyranose increased the activity of alpha-amylase. (C) 2010 Elsevier Ltd. All rights reserved.