Construction of a branched chain at C-3 of a hexopyranoside. Synthesis of miharamycin sugar moiety analogs

Abstract

Synthesis of the conveniently protected epimer at C-3′ of the miharamycin sugar moiety was accomplished starting from the corresponding 3,3′-spiroepoxide. Reaction of the epoxide with lithium cyanide, followed by hydrolysis and spontaneous cyclization, afforded the intermediate deoxylactone methyl 4,6- O-benzylidene-3- C-(carboxymethyl)-α- d-glucopyranoside-3′,2-lactone ( 8). Stereoselective hydroxylation with MoO 5·py·HMPA, reduction with lithium aluminum hydride and cyclization with diethyl azodicarboxylate–triphenylphosphine gave the target molecule methyl 2,3″-anhydro-4,6- O-benzylidene-3- C-[( R)-1,2-dihydroxyethyl]-α- d-glucopyranoside ( 5). Direct reduction of 8 gave other analogs having no C-3′ hydroxyl group together with having a C-3″ hydroxyl group (hemiacetal). In addition, C-3′ epimers were also synthesized through C-3′, C-3″ dihydroxy analogs. Wittig reaction of an appropriate ketosugar with [(ethoxycarbonyl)methylene]triphenylphosphorane leading to a 7:3 Z/E mixture, followed by hydroxylation with osmium tetroxide, reduction and cyclization afforded the target molecule 5 and the miharamycin sugar moiety methyl 2,3″-anhydro-4,6- O-benzylidene-3- C-[( S)-1,2-dihydroxyethyl]-α- d-glucopyranoside. Examination of X-ray data for 5 and its NMR spectroscopy data allowed us to explain a contradiction reported in the literature.