Synthetic Studies of Liposidomycin : Studies of Stereochemistry and biological activity mechanism

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Liposidomycins are a family of novel lipid-containing nucleoside antibiotics of unusual complexity, found in the culture filtrate and mycelia of streptomyces griseosporeus. They are selective antibiotics showing highly specific inhibition toward phospho-N-acetylmuramylpentapeptide transferase that is the primary stage of a lipid cycle in bacterial peptidoglycan synthesis. Liposidomycin B also inhibits in vitro formation of polyprenyl(pyro)phosphate N-acetylglucosamine, an intermediate in glycoconjugate biosynthesis. The structures were proposed on the basis of NMR and mass spectral evidence of degradation compound but the stereochemistry was revealed by X-ray crystallography analysis of caprazamycin that is an analog of liposidomycins.We start to study the synthetic of liposidomycin degradation product. A stereocontrolled synthesis of the liposidomycin diazepanone ring system having a phenyl substituent has been achieved. In the presence of an amino group on the diazepanone ring, the introduction of a uracil group did failed. The N-glycosylation proceeded smoothly to obtain the uracil compound having electron-withdrawing nitrobenzenesulfonamide (Ns) and formyl protecting at an amino group on the diazepanone ring. The detailed examination of the N-glycosylation was accomplished for the total synthesis of liposidomycins.