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

Role of the thiosugar ring in the inhibitory activity of salacinol, a potent natural α-glucosidase inhibitor

“…1 H NMR (800 MHz, D 2 O) d: 3.66-3.83 (10H, m, H-1 0 a, H-1 0 a # , H-1 00 a, H-1 00 b, H-1 00# a, H-1 00# b, H-3 0 a, H-3 0 b, H-3 0 a # , H-3 0 b # , H-1a, H-1b, H-1a # , H-1b # , H-4 00 a, H-4 00 b, H-4 00 a # , H-4 00 b # , H-3 00 and H-3 00# ), 3.86/3.88 (each 0.5H, dd, J = 14.0, 3.0, H-1 0 b and H-1 0 b # ), 4.15 (2H, t, J = 5. Di(2-benzyloxyethyl) [(4S,5S)-2,2-dimethyl-5-sulfooxy-1,3dioxan-4-ylmethyl] sulfonium inner salt (42). A mixture of 41 (302 mg, 1.00 mmol), 33 (275 mg, 1.23 mmol), K 2 CO 3 (32 mg, 0.23 mmol), and HFIP (1.0 mL) was heated under reux for 7 h. Aer removal of the solvent in vacuo, the residue was puried by column chromatography (CHCl 3 : MeOH = 30 : 1) to give the title compound 42 (501 mg, 1.17 mmol, 95%) as a white amorphous.…”

“…Thus, salacinol analogues that surpass the a-glucosidase inhibitory activity of the parent sulfonium salts have been developed, but all of them require a D-arabino-type thiosugar structure for inhibitory activity. While several synthetic methods have been reported, 20,[39][40][41][42][43] it remains difficult to acquire this thiosugar in large quantities for SAR studies due to the number of reaction steps required, limited yield of each step, and accessibility of the starting materials.…”