Stereoselective synthesis of C-glycosides using S-stabilized intermediates

This dissertation is focused on the stereoselective synthesis of β- C-glycosides. C-glycosides, including, glucose derivatives, possess a broad array of physiological activity, e.g., enzyme and platelet aggregation inhibition, antibacterial, antitumor and antiviral activity. These carbohydrate derivatives are also important chiral precursors in synthesis of natural products. During recent years, C-glycosides have generated interest as stable mimics of O-glycosides.; Numerous synthesis routes have been reported for C-glycosides. However, their stereoselective preparation remains a challenge. Two approaches for the stereoselective preparation of β-C-glucosides was achieved using sulfur-stabilized intermediates. In the first approach, arylsulfenyl chloride (ArSCl) adducts of tri-O-benzyl-D-glucal were converted to a mixture of two episulfonium ions, which then reacted with a vinyl ether to form a five-membered sulfonium intermediate. This intermediate was quenched with trimethylsilylcyanide and various Grignard reagents to afford a number of new β-C-glucosides in moderate to high yield and good stereoselectivity (β-gluco : α-manno up to 95:5).; In the second approach, tetra-O-benzyl-exo-D-glucal was alkylated by episulfonium ions prepared from ArSCl adducts of vinyl ethers. The resulting sulfonium/oxonium intermediates were reacted with water, methanol, sodium cyanoborohydride, trimethylsilylcyanide, or sodium azide to afford β- C-glucosides having an additional substituent at the anomeric position.; The structure and stereochemistry of the synthesized C-glucosides were proven using nuclear magnetic resonance spectroscopy, high resolution mass spectrometry, and infrared spectroscopy.