Synthesis of novel analogues of the calicheamicin γ1I and esperamicin A1B oligosaccharides

Abstract

The chemical synthesis of three analogues of the calicheamicin γ₁^I1 and esperamicin A_1B2 oligosaccharides is described in which the carbohydrate ring E is replaced by a basic side chain E′. Our synthetic strategy begins with ABE′ fragment construction which possesses an unusual β N–O glycosidic bond. Glycosylation of the nitrone 20 and the appropriate activated sugar B 13 or 22 gives the disaccharides 23 and 24 respectively. Esperamicin A_1B oligosaccharide analogue 5 is obtained after two deprotection steps of the fragment 24. After removal of the protecting groups of unit 23, the fully deprotected disulfide 33 is reduced and immediately coupled with the deprotected aromatic unit C 30 (or CD 31) to provide the calicheamicin γ₁^I oligosaccharide analogues 3 and 4. We also report the synthesis of hemiacetal 7 in which the thioester function between the CD and B rings is replaced by an ester linkage. This arylsaccharide is a key intermediate required for the synthesis of a novel calicheamicin γ₁^I analogue 6.