Total Synthesis of Glycohexa‐ and Nonaosyl Ceramide with a Sialyl Lea and Sialyl Dimeric Lea Sequence.

Abstract A total synthesis of tumor-associated glycolipid antigen sialyl Lea, and a first total synthesis of glycononaosyl ceramide with a dimeric Lea sequence are described. Regio-and stereoselective coupling of sialyl donor 12 with suitably protected Lea trisaccharide fluoride 17 was performed by orthogonal glycosylation to give the expected tetrasaccharide 18 in good yield. Glycosylation of its acetate 19 with lactose derivative 8 by use of Cp2HfCl2-AgOTf as a promoter, gave the desired hexasaccharide 20. On the other hand, glycosylation between sialyl Lea tetrasacchande donor 34 and Lea pentasaccharide acceptor 35 under the agency of PhSeOTf afforded the desired nonasaccharide 36. After replacement of the benzyl groups in 20 and 36 by acetyl groups, the anomeric acetate was transformed into the α-trichloroacetoimidates 23, 39 and the fluoride derivative 40. The crucial couplings of 23, 39 and 40 with azidosphingosine derivative 3 or ceramide derivative 4 were executed to afford β-glycosides 24 and 41....