Synthesis and Enzyme Inhibitory Activities of Highly Functionalized Pyridylmethyl-C-β-D-Glycosides

Abstract

Several pyridylmethyl-C-β-D-glycosides (3a–3l, 6a, and 6h) were synthesized by refluxing 3-(β-D-glucopyranosyl)/(β-D-cellobiosyl)-propanones and dicyanobenzylidenes with ammonium acetate in anhydrous toluene in moderate to good yields. The reaction involves a C‒C Michael addition of enamine, formed from glycosyl ketone and ammonium acetate, to the dicayanobenzylidene derivative; subsequent dehydrative cyclization; and oxidative aromatization. Two of these prototypes, compounds 3e and 3k, were deacetylated to the respective glucopyranosyl methyl pyridines 4e and 4k with NaOMe/MeOH. The synthesized compounds were screened for their in vitro α-glucosidase inhibitory activities and one of the compounds showed 20% inhibition as compared to standard drug acarbose displaying 39% inhibition.

Keywords:

• Pyridylmethyl-C-β-D-glycosides
• Michael addition
• Knovenagel condensation
• Malononitrile
• α-Glucosidase inhibitors

ACKNOWLEDGEMENTS

This is CDRI communication no. 8061. V.P.P. thanks CSIR, New Delhi, for the award of SRF. We sincerely acknowledge the financial assistance from CSIR, New Delhi and DRDO, New Delhi. SAIF CDRI is also acknowledged for providing spectroscopic data of the compounds.

Notes

*Refers to yield isolated by column chromatography.