SYNTHETIC STUDIES ON SIALOGLYCOCONJUGATES .59. - TOTAL SYNTHESIS OF TUMOR-ASSOCIATED GANGLIOSIDE, SIALYL LE(A)

The first total synthesis of tumor-associated glycolipid antigen, sial yl Le(a), is described, Methylsulfenyl bromide-silver triflate-promote d coupling of 2-(trimethylsilyl)ethyl -(1-->4)-2,3,6-tri-O-benzyl-beta -D-glucopyranoside (2) with methyl O-(methyl ,4,6-tri-O-benzoyl-1-thio -beta-D-galactopyranoside (3) afforded the pentasaccharide 4a and 5a i n good yields. Glycosylation of 4a with methyl 2,3,4-tri-O-benzyl-1-th io-beta-L-fucopyranoside (6) by use of N-iodosuccinimide (NIS) trifluo romethanesulfonic acid (TfOH) as a promoter, gave the desired hexasacc haride 7. Compound 7 was converted into the alpha-trichloroacetimidate 10, via reductive removal of benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroaceton itrile, which, on coupling with S,3R,4E)-2-azido-3-O-benzoyl-4-octadec ene-1,3-diol (11), gave the beta-glycoside 12. Finally, 12 was transfo rmed, via selective reduction of the azide group, coupling with octade canoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 15 in good yield.