title: A convenient synthesis of novel pyranosyl homo-C-nucleosides and their antidiabetic activities.
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.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, CSIR, India.
authors.forename: Surendra Singh
authors.initials: SS
authors.lastname: Bisht
authors.forename: Natasha
authors.initials: N
authors.lastname: Jaiswal
authors.forename: Anindra
authors.initials: A
authors.lastname: Sharma
authors.forename: Seerat
authors.initials: S
authors.lastname: Fatima
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Neha
authors.initials: N
authors.lastname: Rahuja
authors.forename: A K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Vikas
authors.initials: V
authors.lastname: Bajpai
authors.forename: Brijesh
authors.initials: B
authors.lastname: Kumar
authors.forename: Rama P
authors.initials: RP
authors.lastname: Tripathi
mesh_terms: D000818:Animals; D003500:Cyclization; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006031:Glycosylation; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D008956:Models, Chemical; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011725:Pyridines / Q000378:metabolism; D011728:Pyridones / Q000378:metabolism; D051381:Rats; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D009705:Nucleosides; D011714:Pyrans; D011725:Pyridines; D011728:Pyridones; D008687:Metformin; D024981:Glycogen Phosphorylase; D005952:Glucose-6-Phosphatase; D000520:alpha-Glucosidases