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. The reaction product as well as the acetylated form, 1,2:5,6-di-O-isopropylidene 3-O-acetyl ?-D-glucofuranose was characterized per se spectroscopically, chemically and chromatographically. Further, the 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 anhydridepyridine or perbenzoylated 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.