Total Synthesis of Glycohexa- and Nonaosyl Ceramide with a Sialyl Le^a and Sialyl Dimeric Le^a Sequence¹

1. Dedicated to the memory of Professor Alara Hasegawa.

Abstract

A total synthesis of tumor-associated glycolipid antigen sialyl Le^a, and a first total synthesis of glycononaosyl ceramide with a dimeric Le^a sequence are described. Regio-and stereoselective coupling of sialyl donor 12 with suitably protected Le^a 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 Le^a tetrasacchande donor 34 and Le^a 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. Compound 24 was converted to 26 via reduction of the azide group followed by N-acylation. The target gangliosides 1 and 2 were obtained from 26 and 41, respectively, by selective cleavage of the methyl ester, conversion of the N-phthalimido group to the N-acetamido group, and O-deprotection.

1. Dedicated to the memory of Professor Alara Hasegawa.

Notes

1. Dedicated to the memory of Professor Alara Hasegawa.

Dedicated to the memory of Professor Akira Hasegawa