Isoflavone Glycosides: Synthesis and Evaluation as α‐Glucosidase Inhibitors

Abstract On the basis of the structure of 4′,7,8‐trihydroxyisoflavone 7‐ O ‐α‐ D ‐arabinofuranoside (namely A‐76202, 1 ), a Rhodococcus metabolite showing potent inhibitory activities againstthe α‐glucosidases of rat liver microsome ( IC 50 = 0.46 ng/mL), 26 analogs, each with minor variations at the sugar moiety and the isoflavone A and B rings, were readily synthesized. Notably, a new and efficient method was developed for the divergent synthesis of the B‐ring congeners of the isoflavone glycosides by using Suzuki–Miyaura coupling as the final step. Modifications at the sugar moiety and the isoflavone A ring significantly diminish the activity, whereas variations at the B ring are largely tolerated for retaining the potent α‐glucosidase inhibitory activity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)