Masami Iida

TOTAL SYNTHESIS OF GLYCONONAOSYL CERAMIDE WITH A SIALYL DIMERIC LEX SEQUENCE

The first total synthesis of glycononaosyl ceramide with a sialyl dimeric Lex sequence 1 is described. Regio- and stereo-selective glycosylations of sialyl donors 6,7,8 with the suitably protected Lex trisaccharide acceptors 9,10β were performed to give the expected tetrasaccharides 15 and 21, which were converted into the corresponding donors 20 and 22. Boron trifluoride etherate-promoted glycosylation of 20 with pentasaccharide acceptor 11 afforded regioselectively the expected nonasaccharide 23. After replacing benzyl groups of 23 by acetyl groups, the anomeric acetate was transformed into the α-trichloroacetimidate 27. The crucial coupling between 27 and (2S, 3R, 4E-3-O-benzoyl-2-N-tetracosanoylsphingenine 3 was executed to afford completely protected β-glycoside 28. Finally, selective cleavage of the methyl ester and N,O-deprotection of 28 gave the target ganglioside 1.

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....

A total synthesis of glycononaosyl ceramide with a sialyl dimeric Lex sequence

The first total synthesis of glycononaosyl ceramide with a sialyl dimeric Lex sequence 1 is described. Regio- and stereo-selective glycosylations of sialyl donors 6,7,8 with the suitably protected Lex trisaccharide acceptors 9,10β were performed to give the expected tetrasaccharides 15 and 21, which were converted into the corresponding donors 20 and 22. Boron trifluoride etherate-promoted glycosylation of 20 with pentasaccharide acceptor 11 afforded regioselectively the expected nonasaccharide 23. After replacing benzyl groups of 23 by acetyl groups, the anomeric acetate was transformed into the α-trichloroacetimidate 27. The crucial coupling between 27 and (2S, 3R, 4E-3-O-benzoyl-2-N-tetracosanoylsphingenine 3 was executed to afford completely protected β-glycoside 28. Finally, selective cleavage of the methyl ester and N,O-deprotection of 28 gave the target ganglioside 1.