Free-radical and ionic routes towards hydrolytically stable and bioactive C-glycosyl compounds

Photo-initiated addition of glycopyranosyl radicals to such radical acceptors as allyltributyltin, acrylonitrile, or diethyl vinylphosphonate was efficiently achieved to afford stereoselectively α-configured C -glycosyl compounds. With acrylonitrile or diethyl vinylphosphonate, catalytic amounts of organotin were used with NaBH 3 CN in excess. C-1 Sugar dihalides may be converted into the β-configured C -glycosyl analogues in two radical steps (C–C bond formation, reduction), or into bis- C , C -glycosides (two C–C bond forming reactions in one pot). These dihalides also opened the first access to C -glycodienes. C -Glycosyl-ethylphosphonic acids were elaborated into non-isosteric C -glycosyl mimics of natural sugar nucleotide diphosphates, which were evaluated as inhibitors of glycosyl transferases. In another approach, aromatic electrophilic substitution of 1,4-dimethoxybenzene by d -glycopyranosylium ions gave access to C -glycosyl derivatives of 1,4-dimethoxybenzene hydroquinone, and 1,4-benzoquinone. Some were found to inhibit protein tyrosine phosphatase 1B (PTP1B) and glycogen phosphorylase (GP), as shown by enzymatic and crystallographic studies. Extension of the synthetic work led to C -glycosyl-chromanols and C -glycosyl-tocopherols, which have been studied as anti-oxidants.