Journal of Clinical & Experimental Pharmacology

Modulation of the stress molecule, ?-D-glucopyranosyl cholesterol, by 3-O-methylation of the sugar

World Congress on Pharmacology

July 20-22, 2015 Brisbane, Australia

Dumitru Petru Iga

Posters-Accepted Abstracts: Clin Exp Pharmacol

Abstract:

A new glycoside of cholesterol, 3-O-methyl ?-D-glucopyranosyl cholesterol, was synthesized by Koenigs-Knorr glycosylation. D-Glucose was converted to 1, 2:5, 6-di-O-isopropylidene ?-D-glucofuranose by reacting it with acetone in the presence of sulfuric acid and anhydrous copper sulfate. Reaction product was characterized per se spectroscopically, chemically and chromatographically, as well as in acetylated form, as 1, 2:5, 6-di-O-isopropylidene 3-O-acetyl ?-D-glucofuranose. Then 1, 2:5, 6-di-O-isopropylidene 3-O-methyl ?-D-glucofuranose was synthesized by methylation of di-O-isopropylidenic derivative with an excess of methyl iodide/silver oxide in dimethyl formamide. Isopropylidene protecting groups were removed by acidic hydrolysis with acetic acid and 3-O-methyl D-glucose was either peracetylated with acetic anhydride-pyridine or per benzoylated with benzoyl chloride. Peracylated 3-O-methyl ??-D-glucopyranose served as glycosylation donor, either directly or via 1-bromo 1-deoxy 3-O-methyl-tri-O-acyl ?-D-glucopyranose. Glycosylation acceptor was cholesterol, and chemical promoters were either dibutyl etherated boron trifluoride or cadmium carbonate. The glycoside of cholesterol was characterized by NMR spectroscopy. The NMR signals indicated 3-O-methyl-tri-O-acetyl ?-D-glucopyranosyl cholesterol: 100.0/4.39 (d, 7.7 Hz, 1H) (C1/H1); 72.1/4.84 (dd, 8Hz, 1Hz, 1H) (C2/H2); 80.0/4.92 (t, 10 Hz, 1H) (C3/H3); 69.1/4.10 (dd, 5Hz, 7Hz, 1H) (C4/ H4); 81.3/3.98 (dd, 2Hz, 10Hz, 1H) (C5/H5); 62.6/3.44 (C6/H6a); 62.6/3.39 (C6/H6b); 58.3/3.29 (s, 3H) (CH3 etheric group); 72.0/3.46 (C3/H3 cholesterol); 122.1/5.26 (d, 5Hz) (C6/H6 cholesterol); 11.99/0.58 (C18/H18 cholesterol); 18.86/0.90 (C19/ H19 cholesterol). Acyl protecting groups were removed by Z�mplen hydrolysis. The glycosylation product gave 3-O-methyl- D-glucose and cholesterol by acidic hydrolysis.