Synthesis and biological evaluation of deoxy salacinols, the role of polar substituents in the side chain on the alpha-glucosidase inhibitory activity

Three analogs (5, 6, and 7) lacking polar substituents in the side chain of a naturally occurring alpha-glucosidase inhibitor, salacinol (1a), were synthesized by the coupling reaction of a thiosugar, 1,4-dideoxy-1,4-epithio-D-arabinitol (3), with cyclic sulfates (8, 9, and 10), and their alpha-glucosidase inhibitory activities were examined. All these simpler analogs (5, 6, and 7) showed less inhibitory activity compared to 1a, and proved the importance of cooperative role of the polar substituents for the alpha-glucosidase inhibitory activity. A practical synthetic route to 3 starting from D-xylose is also described.