Synthesis of uridine 5'-(2-acetamido-2,4-dideoxy-4-fluoro-alpha-D-galactopyranosyl) diphosphate and uridine 5'-(2-acetamido-2,6-dideoxy-6-fluoro-alpha-D-glucopyranosyl) diphosphate.
Benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside was converted into its 4-O-(methylsulfonyl) derivative (2) by treatment with methanesulfonyl 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-alpha-D-galactopyranosi de, 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 approximately 50 degrees 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 alpha-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-alpha-D-galactopyranosy l phosphate (7), and that of 12 gave 2-acetamido-3,4-di-O-acetyl-2,6-dideoxy-6-fluoro-alpha-D-glucopyranosyl phosphate (13). Coupling of 7 and 13 with uridine 5'-monophosphomorpholidate in dry pyridine at approximately 37 degrees, followed by O-deacetylation, furnished the title compounds, respectively, isolated and characterized as their respective dilithium salts.
Thomas
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RL
Department of Gynecologic Oncology, Roswell Park Memorial Institute, Buffalo, New York 14263.
Abbas
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SA
Matta
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KL
D002236:Carbohydrate Conformation; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009904:Optical Rotation; D014536:Uridine Diphosphate N-Acetylgalactosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D014539:Uridine Diphosphate Sugars / Q000138:chemical synthesis*
D007202:Indicators and Reagents; D014539:Uridine Diphosphate Sugars; C059430:uridine 5'-(2-acetamido-2,4-dideoxy-4-fluorogalactopyranosyl)diphosphate; C059431:uridine 5'-( 2-acetamido-2,6-dideoxy-6-fluoroglucopyranosyl)diphosphate; D014537:Uridine Diphosphate N-Acetylglucosamine; D014536:Uridine Diphosphate N-Acetylgalactosamine