Synthetic studies in butenonyl C-glycosides: Preparation of polyfunctional alkanonyl glycosides and their enzyme inhibitory activity

• Published in: Bioorganic & medicinal chemistry letters 2009-05, Vol.19 (10), p.2699-2703
• Main Authors: Bisht, Surendra Singh, Fatima, Seerat, Tamrakar, Akhilesh K., Rahuja, Neha, Jaiswal, Natasha, Srivastava, Arvind K., Tripathi, Rama P.
• Format: Article
• Language: English
• Subjects: Acarbose; Alkanonyl glycosides; Alkenoyl glycosides; alpha-Glucosidases - metabolism; Animals; Biological and medical sciences; Blood Glucose - metabolism; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; General and cellular metabolism. Vitamins; Glucose-6-phosphatase; Glucose-6-Phosphatase - antagonists & inhibitors; Glucose-6-Phosphatase - metabolism; Glycogen phosphorylase; Glycogen Phosphorylase - antagonists & inhibitors; Glycogen Phosphorylase - metabolism; Glycoside Hydrolase Inhibitors; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - pharmacology; Medical sciences; Metformin; Michael reaction; Pharmacology. Drug treatments; Rats; α-Glucosidase
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.03.136

A simple synthesis of phenyl butenoyl C-glycosides has been achieved by Aldol condensation of peracetylated glycosyl acetones with aromatic aldehydes followed by deacetylation with methanolic NaOMe. The selected butenoyl C-glycosides on conjugate addition of diethyl malonate resulted in polyfunctional alkanonyl glycosides in good yields. The butenoyl C- and alkanoyl C-glycosides were evaluated for their α-glucosidase, glucose-6-phosphatse and glycogen phosphorylase enzyme inhibitory activities in vitro. Three of the synthesized ( 3, 5 and 9) showed potent enzyme inhibitory activities as compared to standard drugs. Compounds 3, 5 and 9 were evaluated in vivo too displaying significant activity as compared to standard drugs acarbose and metformin.