5'-Azido and 5'-fluoro alpha-nucleosides as analogues of AZT and FLT.
5-Azido-2,5-dideoxy-beta-D-erythro-pentofuranosyl nucleosides 10 and their corresponding alpha-anomers 11 have been synthesized by condensation of methyl 3-O-acetyl-5-azido-2,5-dideoxy-beta-D-erythro-pentofuranoside (7) with silylated nucleobases followed by deprotection with methanolic ammonia. Reaction of silylated thymine (19) with methyl 2,3-di-O-benzoyl-5-deoxy-5-fluoro-D-arabino-pentofuranoside (15) and methyl 5-azido-2,3-di-O-benzoyl-5-deoxy-alpha-D-arabino-pentofuranoside (17 alpha) afforded a mixture of the alpha-nucleosides 20 and the acyclo nucleosides 5-fluoro- and 5-azido-2,3-O-dibenzoyl-5-deoxy-1-O-methyl-1-(thymin-1-yl)-D -arabinitol (22). Compounds 20 and 22 were deprotected with methanolic ammonia to give the acyclic nucleosides 21 and 23, respectively. The new nucleosides were inactive against HSV-1 and HIV-1.
Schmidt
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Department of Chemistry, Odense University, Denmark.
Pedersen
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EB
Nielsen
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C
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry*; D001386:Azides / Q000737:chemistry; D002460:Cell Line; D002478:Cells, Cultured; D015224:Dideoxynucleosides / Q000737:chemistry*; D005459:Fluorides / Q000737:chemistry; D015497:HIV-1; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D018139:Simplexvirus; D015215:Zidovudine / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D001386:Azides; D015224:Dideoxynucleosides; D009705:Nucleosides; D015215:Zidovudine; C002854:alovudine; D005459:Fluorides