Synthetic Studies of Rifamycins. III. The Partial Synthesis of Rifamycin Ansa-chain Compounds from Their Degradation Products

Article abstract of DOI:10.1246/bcsj.54.1743

The ansa-chain compound methyluronate (1a) and its (R)-2-bromo derivative, 1b, were transformed into the corresponding 7,9-diacetate 3a and 3b or the 7,9-acetonide 7a and 7b.The ozonolysis of 3a or 3b gave methyl 7,9-di-O-acetyl-2,4,6,8,10-pentadeoxy-4,6,8,10-tetra-C-methyl-3-O-methyl-L-manno-β-D-galacto-undecodialdopyranoside-(1,5) (4a) or its (R)-2-bromo derivative (4b) respectively.The Wittig condensation of 4b with (methoxycarbonyl methylene)triphenylphosphorane, followed by debromination with tributylstannane, afforded methyl uronate (6a).The diisobutylaluminium hydride reduction of 6a, followed by acetonation, gave methyl 2,4,6,8,10,11,12-heptadeoxy-7,9-O-isopropylidene-4,6,8,10-tetra-C-methyl-3-O-methyl-L-manno-β-D-galacto-(E)-11-tridecenopyranoside-(1,5) (10a).The allylic alcohol, 10a, was converted into the allylic bromide, 12a, which then yielded the triphenylphosphonium bromide, 13a.The Wittig condensation of the reactive ylide generated from 13a with methyl pyruvate afforded a 4 : 5 mixture of 7a and its 13E-isomer.The partial synthesis of 1a was accomplished by the selective hydrolysis of the 7a isolated from the mixture.