Glycosylation of Branched Amino and Nitro Sugars. 2. Synthesis of the Cororubicin Trisaccharide

Abstract

The synthesis of the nitro-sugar-containing trisaccharide found in the antibiotic cororubicin is described. This trisaccharide contains the nitro sugar l-decilonitrose which is attached to two digitoxose residues (a dideoxy sugar) by β-1,4 and α-1,4 linkages. The target trisaccharide synthesized was methyl 2,6-dideoxy-α-l-lyxo-hexopyranosyl-(1→4)-2,3,6-trideoxy-3-C-methyl-3-nitro-β-l-ribo-hexopyranosyl-(1→4)-2,6-dideoxy-α-l-lyxo-hexopyranoside. The principle features of the synthesis are the use of an O-benzylhydroxylamino sugar as the precursor to the nitro sugar decilonitrose and as both the acceptor and donor in glycosyations, a β-selective glycosylation by means of a thioglycoside donor, and novel functional group transformations carried out on the assembled trisaccharide. These include oxidative cleavage of the O-benzylhydroxylamino group to nitro, carried out with dimethyldioxirane in one step. This transformation proved critical in completing the synthesis, which is the first reported of one of the decilonitrose-containing trisaccharides found in antibiotics.