Total synthesis of a modified ganglioside, de-N-acetyl GM2.

Regio- and stereo-selective glycosylation of a sialyl donor 6 that carries a N-phthaloyl protecting group at C-5 with a lactosyl acceptor 7 armed with a pivaloyl group at O-2a was performed to give the expected glycotrioside 5. Subsequent glycosylation of 5 with 2-azido galactosyl donor 4 gave glycotetraosyl derivatives 18 and 19. After conversion of 18 into imidates 25 and 26, coupling with (2S,3R,4E)-3-O-benzoyl-2-N-tetracosanoylsphingenine (2) was executed to afford completely protected ganglioside analogues 27 and 28. Selective cleavage of the methyl ester and N,O-deprotection gave the target de-N-acetyl GM2 (1).