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

Synthesis of the conveniently protected epimer at C-3' of the miharamycin s ugar moiety was accomplished starting from the corresponding 3,3'-spiroepox ide. Reaction of the epoxide with lithium cyanide, followed by hydrolysis a nd spontaneous cyclization, afforded the intermediate deoxylactone methyl 4 ,6-O-benzylidene-3-C-(carboxymethyl)-alpha-D-glucopyranoside-3',2-lactone ( 8). Stereoselective hydroxylation with MoO5. py . HMPA, reduction with lith ium aluminum hydride and cyclization with diethyl azodicarboxylate-tripheny lphosphine gave the target molecule methyl 2,3 "-anhydro-4,6-O-benzylidene- 3-C-[(R)-1,2-dihydroxyethyl]-alpha-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 sy nthesized through C-3', C-3 " dihydroxy analogs. Wittig reaction of an appr opriate ketosugar with [(ethoxycarbonyl)methylene]triphenylphosphorane lead ing to a 7:3 Z/E mixture, followed by hydroxylation with osmium tetroxide, reduction and cyclization afforded the target molecule 5 and the miharamyci n sugar moiety methyl 2,3 "-anhydro-4,6-O-benzylidene-3-C-[(S)-1,2-dihydrox yethyl]-alpha-D-glucopyranoside. Examination of X-ray data for 5 and its NM R spectroscopy data allowed us to explain a contradiction reported in the l iterature. (C) 2000 Elsevier Science Ltd. All rights reserved.