Aminoglycoside antibiotics: Synthesis of pseudotrisaccharides derived from neamine and paromamine

Abstract

Pseudotrisaccharides of paromamine having a 6-O-(β-D-ribofuranosyl) and 6-O-(α-D-arabinofuranosyl) moieties were prepared from appropriately N,O-substituted derivatives of paromamine by glycosylation reactions. Selective functionalization at C-6′ in 6-O-(β-D-ribofuranosyl)paromamine led to the corresponding neamine-containing pseudotrisaccharide. None of these semisynthetic aminoglycosides possessed antibacterial activity, although at least one of them has been shown to be a substrate for the phosphotransferases I and II. The unnatural attachment of a pentofuranosyl moiety at C-6 of the 2-deoxystreptamine unit in these pseudotrisaccharides is, therefore, detrimental to their antibacterial action, unlike amino sugar containing analogs at the same position.