Synthesis of fluoro derivatives of 2-amino-2-deoxy-D-galactose and -D-glucose

Abstract

Selective fluoride displacement of the 6-mesyloxy group of methyl 2-benzamido-3-O-benzyl-2-deoxy-4,6-di-O-mesyl-α-D-glucopyranoside 4 gave the 6-fluoride 5. Subsequent removal of the blocking substituents afforded 2-amino-2,6-dideoxy-6-fluoro-D-glucose, isolated as its hydrochloride 11 and its N-acetyl derivative 12. Nucleophilic displacement of the remaining 4-mesyloxy group of the intermediary 6-fluoro-4-mesylate 5, by benzoate anion afforded derivatives of 2-amino-2,6-deoxy-6-fluoro-D-galactose (18). An interplay of similar substitutions on 4 gave, after deprotection, methyl 2-acetamido-4,6-difluoro-2,4,6-trideoxy-α-D-galactopyranoside (22), methyl 2-acetamido-3-O-acetyl-4,6-difluoro-2,4,6-trideoxy-α-D-glucopyranoside (27), and methyl 2-benzamido-3-O-benzyl-6-fluoro-2,4,6-trideoxy-β-L-threo-hex-4-enopyranoside(28).Methyl 2-acetamido-2,4-dideoxy-4-fluoro-α-D-glucopyranoside diacetate (31) was synthesized from the 4-O-mesyl-6-O-trityl-galactopyranoside 29.