Synthesis of uridine 5′-(2-acetamido-2,4-dideoxy-4-fluoro-α-d-galactopyranosyl) diphosphate and uridine 5′-(2-acetamido-2,6-dideoxy-6-fluoro-α-d-glucopyranosyl) di-phosphate

Benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-d-glucopyranoside was converted into its 4-O-(methylsulfonyl) derivative (2) by treatment with methane-sulfonyl chloride in pyridine. Displacement of the methylsulfonyloxy group of 2 with fluoride ion afforded benzyl 2-acetamido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-α-d-galactopyranoside, which on hydrogenolysis, followed by acetylation, furnished 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-d-galactopyranose. Treatment of this and of 2-acetamido-1,3,4-tri-O-acetyl-2,6-dideoxy-6-fluoro-d-glucopyranose with trimethylsilyl trifluoromethanesulfonate in 1,2-dichloroethane at ∼50° afforded the 4-deoxy-4-fluoro- or the 6-deoxy-6-fluoro-oxazolines (5) and (11), respectively. Reaction of 5 and 11 with dibenzyl phosphate in 1,2-dichloroethane produced the α-linked dibenzyl phosphate derivatives 6 and 12, respectively. Catalytic hydrogenation of 6 provided 2-acetamido-3,6-di-O-acetyl-2,4-dideoxy-4-fluoro-α-d-galactopyranosyl phosphate (7), and that of 12 gave 2-acetamido-3,4-di-O-acetyl-2,6-dideoxy-6-fluoro-α-d-glucopyranosyl phosphate (13). Coupling of 7 and 13 with uridine 5′-monophosphomorpholidate in dry pyridine at ∼37°, followed by O-deacetylation, furnished the title compounds, respectively, isolated and characterized as their respective dilithium salts.