Stereoselective synthesis of carba- and C-glycosyl analogs of fucopyranosides

Fucopyranoside analogs with methylene groups instead of endo- or exo-anomer ic oxygens, carba- and C-fucopyranosides, respectively, were synthesized. F or the synthesis of 5a-carba-L-fucose (1) two approaches were studied, whic h shared a common cyclitol building block (8), obtained from a SmI2-promote d carbocyclization of a D-mannitol derivative. The first route made use of a Stork radical cyclization onto a conduritol derivative 13 as the key step , which failed to give the silyl ether ring. The second route furnished the target 1, and involved regioselective elimination of a cyclic sulfate 9, a nd stereoselective hydrogenation of a double bond, controlled by substituti on on the substrate. For the synthesis of 1-C-fucopyranosides (37, 38, and 42) a new method based on the use of fucosyl phenyl sulfoxides (35 and 41) was employed. An anomeric carbanion is generated through phenyl-sulfinyl-li thium exchange, which reacted with electrophiles with retention of configur ation at the anomeric center. The required fucosyl sulfoxides were prepared from L-fucose by highly stereoselective thioglycosylation reactions.