A convenient synthesis of novel pyranosyl homo-C-nucleosides and their antidiabetic activities

Surendra Singh Bisht; Natasha Jaiswal; Anindra Sharma; Seerat Fatima; Rahul Sharma; Neha Rahuja; A K Srivastava; Vikas Bajpai; Brijesh Kumar; Rama P Tripathi

doi:10.1016/j.carres.2011.03.006

A convenient synthesis of novel pyranosyl homo-C-nucleosides and their antidiabetic activities

Carbohydr Res. 2011 Jul 15;346(10):1191-201. doi: 10.1016/j.carres.2011.03.006. Epub 2011 Mar 8.

Authors

Surendra Singh Bisht¹, Natasha Jaiswal, Anindra Sharma, Seerat Fatima, Rahul Sharma, Neha Rahuja, A K Srivastava, Vikas Bajpai, Brijesh Kumar, Rama P Tripathi

Affiliation

¹ Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, CSIR, India.

PMID: 21550025
DOI: 10.1016/j.carres.2011.03.006

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cyclization
Diabetes Mellitus, Experimental / chemically induced
Diabetes Mellitus, Experimental / drug therapy
Diabetes Mellitus, Experimental / pathology
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / therapeutic use*
Glucose-6-Phosphatase / antagonists & inhibitors
Glucose-6-Phosphatase / metabolism
Glycogen Phosphorylase / antagonists & inhibitors
Glycogen Phosphorylase / metabolism
Glycoside Hydrolase Inhibitors
Glycosylation
Hypoglycemic Agents / chemical synthesis*
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / therapeutic use
Metformin / therapeutic use
Models, Chemical
Nucleosides / chemical synthesis*
Nucleosides / chemistry
Nucleosides / therapeutic use
Pyrans / chemical synthesis*
Pyrans / chemistry
Pyrans / therapeutic use
Pyridines / metabolism
Pyridones / metabolism
Rats
alpha-Glucosidases / metabolism

Substances

Enzyme Inhibitors
Glycoside Hydrolase Inhibitors
Hypoglycemic Agents
Nucleosides
Pyrans
Pyridines
Pyridones
Metformin
Glycogen Phosphorylase
Glucose-6-Phosphatase
alpha-Glucosidases