Synthesis of some monodeoxyfluorinated methyl and 4-nitrophenyl α-d-mannobiosides and a related 4-nitrophenyl α-d-mannotrioside

Treatment of methyl 3,4,6-tri-O-benzyl-2-O-(2,3,4-tri-O-acetyl-α-d-mannopyranosyl)-α-d-mannopyranoside with N,N-diethylaminosulfur trifluoride (Et₂NSF₃), followed by O-deacetylation and catalytic hydrogenolysis, afforded methyl 2-O-(6-deoxy-6-fluoro-α-d-mannopyranosyl)-α-d-mannopyranoside (8). Methyl 6-deoxy-6-fluoro-2-O-α-d-mannopyranosyl-α-d-mannopyranoside (11) was similarly obtained from methyl 3-O-benzyl-2-O-(2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl-α-d-mannopyranoside. 1,2,3,4-Tetra-O-acetyl-6-deoxy-6-fluoro-β-d-mannopyranose (13), used for the synthesis of the 4-nitrophenyl analogs of 8 and 11, as well as their 3-O-linked isomers, was obtained by treatment of 1,2,3,4-tetra-O-acetyl-β-d-mannopyranose with Et₂NSF₃. Treatment of 13 with 4-nitrophenol in the presence of tin(IV) chloride, followed by sequential O-deacetylation, isopropylidenation, acetylation, and cleavage of the acetal group, afforded 4-nitrophenyl 4-O-acetyl-6-deoxy-6-fluoro-α-d-mannopyranoside (18). Treatment of 13 with HBr in glacial acetic acid furnished the 6-deoxy-6-fluoro bromide 19. Glycosylation of diol 18 with 20 gave 4-nitrophenyl 4-O-acetyl-6-deoxy-6-fluoro-3-O- (21) and -2-O-(2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl)-α-d-mannopyranoside (23) in the ratio of ∼2:1, together with a small proportion of a branched trisaccharide. 4-Nitrophenyl 4,6-di-O-acetyl-α-d-mannopyranoside was similarly glycosylated with bromide 19 to give 4-nitrophenyl 4,6-di-O-acetyl-3-O- and -2-O-(2,3,4-tri-O-acetyl-6-deoxy-6-fluoro-α-d-mannopyranosyl)-α-d-mannopyranoside. The various di- and tri-saccharides were O-deacetylated by Zemplén transesterification.