Synthesis of analogues of salacinol containing a carboxylate inner salt and their inhibitory activities against human maltase glucoamylase

The syntheses of analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described. Salacinol is a sulfonium ion with an internal sulfate counterion. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri-O-benzyl-4-thio-d- or l-arabinitol at the least hindered carbon of 4,5-anhydro-2,3-O-isopropylidene-d-ribonic acid benzyl ester to yield coupled adducts. Deprotection of the coupled products gives the target compounds. The compound derived from d-arabinitol inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a Ki value of 10 ± 1 μM.

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