Isoflavone glycosides: Synthesis and evaluation as α-glucosidase inhibitors

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 against the 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, 2008.postprin