First total synthesis of α-(2 → 3)/α-(2 → 6)-disialyl lactotetraosyl ceramide and disialyl Lewis A ganglioside as cancer-associated carbohydrate antigens

The first total synthesis of alpha-(2 --> 3)/alpha-(2 --> 6)-disialyl lactotetraosyl (DSLc(4)) ceramide and alpha-(2 --> 3)/alpha-(2 --> 6)-disialyl Lewis A (DSLe(a)) ganglioside as cancer-associated antigens is described. The suitably protected lactotriose (Lc(3)) derivatives were successively glycosylated with sialic acid, sialyl-alpha-(2 --> 3)-D-galactose and/or L-fucose donors in a regio- and stereo-selective manner, to give the protected type I hexa- and hepta-saccharides, respectively, which were then converted to the target gangliosides by the introduction of ceramide and subsequent complete deprotection. (C) 2002 Elsevier Science Ltd. All rights reserved.