Synthesis of a sialyl-alpha-(2-->6)-lactosamine trisaccharide with a 5-amino-3-oxapentyl spacer group at C-1I.
As part of a continuing study aimed to achieve improved monoclonal antibodies against carcinoembryonic antigen (CEA) carbohydrate fragments, the synthesis of a sialyl-(2-->6)-lactosamine trisaccharide with a 5-amino-3-oxapentyl spacer group at C-1I has been developed. Two different routes to access this target are described. For this purpose 5-azido-3-oxapentyl 6-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside (4) was selectively beta-galactosylated in 81% yield using the crystalline 2,3-di-O-acetyl-4,6-O-benzylidene-alpha-D-galactopyranosyl trichloroacetimidate as the donor, taking advantage of the bulky phthalimido group at C-2 of 4. On the other hand, galactosylation of the suitable protected acceptor 5-azido-3-oxapentyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside with the crystalline 2,3-di-O-acetyl-4,6-O-benzylidene-alpha-D-galactosyl bromide renders the corresponding disaccharide in a moderate 58% yield. Despite the fact that the first strategy, unlike the second one, requires a hydrazinolysis-acetylation reaction at the disaccharide stage, it was found to be more convenient to access the disaccharide acceptor. Sialylation was performed using a thiophenyl donor under an NIS-TfOH activation procedure in acetonitrile to give a mixture of alpha and beta trisaccharides in 49 and 16% yields, respectively.
Figueroa-Pérez
S
S
Laboratory of Synthetic Antigens, Facultad de Química, Universidad de La Habana, Havana, Cuba.
Vérez-Bencomo
V
V
D000911:Antibodies, Monoclonal; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000276:immunology; D007202:Indicators and Reagents; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000737:chemistry
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007202:Indicators and Reagents; D014312:Trisaccharides