Diastereoselective Synthesis of Salacinol-Type α-Glucosidase Inhibitors

Article abstract of DOI:10.1021/acs.joc.7b02566

A facile and highly diastereoselective approach toward the synthesis of potent salacinol-type α-glucosidase inhibitors, originally isolated from plants of the genus "Salacia", was developed using the S-alkylation of thiosugars with epoxides in HFIP (～90%, dr, α/β = ～ 26/1). The dr ratio of the product was significantly improved by the protocol as compared to that of the conventional S-alkylation of thiosugars (dr, α/β = ～ 8/1). The protocol could be used for gram scale synthesis of the desired compounds. The 3′-O-benzylated salacinol analogs, which are the most potent in vitro inhibitors to date, were synthesized and evaluated in vivo; all analogs suppressed blood glucose levels in maltose-loaded mice, at levels comparable to those of the antidiabetic agent, voglibose.