Synthesis and glycosidase inhibitory activities of chain-modified analogues of the glycosidase inhibitors salacinol and blintol

The synthesis of chain-modified analogues of the naturally-occurring glycosidase inhibitor, salacinol, and its selenium analogue, blintol is described. The modification consists of a frame shift of the sulfate moiety by one carbon atom in the zwitterionic structures as well as an extension of the acyclic chain to five carbons. The target molecules were synthesized by alkylation of 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio (or seleno)-d-arabinitol at the ring heteroatom by 2,3,5-tri-O-p-methoxybenzyl d- or l-xylitol-1,4-cyclic sulfate, followed by deprotection with trifluoroacetic acid. Two of the four compounds inhibit recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with K i values of 20 ± 4 and 53 ± 5 μM.