Syntheses of Peptidyl Nucleoside Antibiotics

Abstract

Polyoxins and nikkomycins are an important class of peptidyl nucleoside antibiotics isolated from the culture broths of Streptomyces cacaoi var. asoensis and Streptomyces tendae. For the syntheses of these antibiotics, efficient syntheses of 1-(5-amino-5-deoxy-β-D-allofurano-uronosyl)pyrimidines such as thymine polyoxin C, uracil polyoxin C and their congeners as a basic component corresponding to the right half were achieved based on the nucleophic 1,2-addition to methyl 2,3-O-isopropylidene-β-D-ribopentodialdo-1,4-furanoside. Then the syntheses of polyoxamic acid derivatives and their congeners corresponding to the left acid part were carried out based on 1,2-addition of carbon nucleophile to 4-O-protected-2,3-O-isopropylidene-L-threose. Coupling reaction of the activated ester derived from the left half acid part and amine part derived from the right half gave the N,O-protected peptidyl nucleoside congeners which were subjected to deprotection to afford polyoxins B, D, J, L, M, C and nikkomycin B.