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 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)-alpha-D-glucopyranoside-3',2-lacto ne (8). Stereoselective hydroxylation with MoO5 x py x 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]-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 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]-alpha -D-glucopyranoside. Examination of X-ray data for 5 and its NMR spectroscopy data allowed us to explain a contradiction reported in the literature.
Rauter
A
A
Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal. aprauter@mail.telepac.pt
Ferreira
M
M
Borges
C
C
Duarte
T
T
Piedade
F
F
Silva
M
M
Santos
H
H
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D005960:Glucosides / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D011687:Purines; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D000900:Anti-Bacterial Agents; D005960:Glucosides; D011687:Purines; C013810:amipurimycin