Synthesis of C-Glycosylic Compounds Using Three-Membered Cyclic Intermediates

Numerous methods for preparation of C-glycosylic compounds (C-glycosides) have been developed. One general approach to the synthesis of these important O-glycoside analogs is based on the use of three-membered cyclic intermediates. The review is focused on the application of glycal and exo-glycal derived epoxides and episulfonium and iodonium ions for preparation of C-glycosides. Reactions of glycal epoxides with organocuprates, Grignard and organolithium reagents, allylsilane, sodio malonate, and lithium alkynyl derivatives have been shown to be convenient for stereoselective synthesis of both a- and b-C-glycosides. The unprotected C(2)-hydroxyl group in the products can be removed in two steps providing an easy excess to 2-deoxy-C-glycosides. Electrophilic addition of arylsulfenyl chloride (ArSCl) to glycals has afforded 2-(arylthio)pyranosyl chlorides. Upon the treatment with a Lewis acid, the chlorides have been converted to episulfonium-like intermediates. Reactions of the latter species with silyl enol ethers, TMSCN, allylsilanes, vinyl ethers, and heteroaromatic compounds have opened a new synthetic route to 2-(arylthio)-b-C-glycosides having a variety of functional groups in the lateral chain. The 2-arylthio group in the products can be selectively removed using Raney Ni or n-Bu3SnH/AIBN. Episulfonium ions generated from ArSCl adducts of 1-methylene sugars have reacted with O- and C-nucleophiles to afford O-ketopyranosides and 1,1-dialkyl C-glycosides, respectively. Acid catalyzed and nucleophilic ring openings of spiro epoxides obtained from exo-glycals have occurred with opposite stereoselectivity. Iodonium-promoted reactions of exo-glycals have led to O-ketopyranoside derivatives.