Regioselective synthesis of a glycomimetic trisaccharide of Sialyl Lewis (sLe x)

Sialyl Lewis (sLe x) is the smallest naturally occurring carbohydrate ligand that binds to E-Selectin on the activated endothelium. We report here the total synthesis of acetic acid-sLe x analog ( 12), for testing as a therapeutic agent. Methoxyethyl 4- O-(3,4- O-isopropylidene-β- d-galactopyranosyl)-β- d-glucopyranoside ( 3) was prepared starting from the methoxyethyl-β- d-lactoside ( 2), which was selectively benzoylated to give the methoxyethyl 2,6-di- O-benzoyl-4- O-(2,6-di- O-benzoyl-3,4- O-isopropylidene-β- d-galactopyranosyl)-β- d-glucopyranoside ( 4). Glycosylation of acceptor 4 with methyl 2,3,4-tri- O-benzyl-1-thio-β- l-fucopyranoside ( 5) in the presence of cupric bromide and tetrabutylammonium bromide afforded the corresponding methoxyethyl 2,6-di- O-benzyl-3- O-(2,3,4-tri- O-benzyl-α- l-fucopyranosyl)-4- O-(2,6-di- O-benzyl-3,4- O-isopropylidene-β- d-galactopyranosyl)-β- d-glucopyranoside ( 6). Selective removal of the 4″,6″- O-isopropylidene group from 6 gave the deprotected trisaccharide 7. The regioselective esterification of O-3″ of trisaccharide 8 (obtained from the dibutylstannylene derivative of 7) with benzyl-2-bromoacetate and tetrabutylammonium bromide afforded the 3″- O-carbobenzyloxymethyl trisaccharide derivative 9, which on saponification and hydrogenolysis with palladium–charcoal afforded the target trisaccharide 12 glycomimetic of Sialyl Lewis (sLe x) trisaccharide omitting the sialic acid moiety.