A Convenient Synthesis of Novel Pyranosyl Homo-C-Nucleosides and Their Antidiabetic Activities

A series of pyranosyl homo-C-nucleosides have been synthesized by reaction of butenonyl C-glycosides (5a-5j, and 8) and cyanoacetamide in presence of t-BuOK followed by further modifications. The reaction proceeds by Michael addition of cyanoacetamide to the butenonyl C-glycosides and subsequent dehydrative cyclization and oxidative aromatization to give glycosylmethyl pyridones (6a-6j, 7a-7j, 9, and 10). The glycosylmethyl pyridones (6a-6e) on reaction with POCl(3) under reflux gave respective glycosylmethyl pyridines (11a-11e and 12a-12e) in good yields. The synthesized compounds were screened for their in vitro α-glucosidase, glucose-6-phosphatase and glycogen phosphorylase inhibitory activities. One of the pyridylmethyl homo-C-nucleoside, compound 11d, displayed 52% inhibition of glucose-6-phosphatase as compared to the standard drug sodium orthovanadate while compound 12a showed a significant antihyperglycemic effect of 17.1% in the diabetic rats as compared to the standard drug metformin.