Efficient Synthesis of a High-Mannose-Type Pentasaccharide and Hexasaccharide Related to N-Glycans

Abstract

Two high-mannose-type N-glycans, Man5 and Man6 oligosaccharides, were concisely synthesized from 4-methoxyphenyl α- d -mannopyranoside via 9 and 12 steps, and in 23% and 15% overall yields, respectively. The efficiency of the synthesis relies on the large-scale preparation of a key disaccharide intermediate, 4-methoxyphenyl 3,6-di-O-allyloxycarbonyl-2,4-di-O-benzoyl-α- d -mannopyranosyl-(1→6)-2,4-di-O-benzoyl-α- d -mannopyranoside, with two hydroxyl groups partially masked by allyloxycarbonyl protection. The disaccharide was obtained in 84% yield by regioselective glycosylation of 4-methoxyphenyl 2,4-di-O-benzoyl-α- d -mannopyranoside with 3,6-di-O-allyloxycarbonyl-2,4-di-O-benzoyl-α- d -mannopyranosyl trichloroacetimidate. The disaccharide could be easily transformed to a tetrasaccharide diol acceptor via condensation of 4-methoxyphenyl 3,6-di-O-allyloxycarbonyl-2,4-di-O-benzoyl-α- d -mannopyranosyl-(1→6)-2,4-di-O-benzoyl-α- d -manno­pyranoside with a disaccharide donor followed by removal of the two allyloxycarbonyl groups in the resultant tetrasaccharide, or be converted into a triol acceptor by direct deallyloxycarbonylation. Glycosylation of the triol or diol acceptor with 2,3,4,6-tetra-O-benzoyl-α- d -manno­pyranosyl trichloroacetimidate provided the desired protected pentasaccharide and hexasaccharide in one step in 64% and 67% yields, respectively. Finally, the target compounds, pentasaccharide and hexasaccharide, were obtained after deprotection. The structures of target compounds and intermediates were characterized by 1H NMR, 13C NMR, and HRMS.