Synthesis of linear-B saccharopeptides via enzymatic galactosylation of non-natural glucosamide acceptors

A series of d- and l-glycopyranuronic acids are coupled to glucosamines to give saccharopeptides. These ‘disaccharides’, in which the acetyl moiety of the natural N-acetyl-glucosamine is replaced by various sugar acids, turned out to be surprisingly good substrates for β(1-4)-galactosyl-transferase and α(1-3)-galactosyl-transferase. The enzymes transfer successively two galactose units from the donor UDP-galactose onto these acceptor substrates, despite the far reaching alterations, regio- and stereospecifically in the expected manner to give linear-B saccharopeptides. β(1-4)- and recombinant α(1-3)-galactosyl-transferases are used on a preparative scale to glycosylate a series of saccharopeptides to give non-natural linear-B trisaccharide analogues.