TY - JOUR
T1 - Nucleosides. 146. L-methyl-5-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)uracil, The C-nucleoside Isostere of the Potent Antiviral Agent L-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)thymine (fmau). Studies Directed Toward The Synthesis of 2'-deoxy-2'-substituted Arabino Nucleosides. 6
AU - Pankiewicz, Krzysztof W.
AU - Nawrot, Barbara
AU - Gadler, Hakan
AU - Price, Richard W.
AU - Watanabe, Kyoichi A.
PY - 1987/12/1
Y1 - 1987/12/1
N2 - The synthesis of 5-(2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-/?-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-0-acetyl-2'-0-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur(l+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-0-acetyl-2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2.
AB - The synthesis of 5-(2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-/?-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-0-acetyl-2'-0-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur(l+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-0-acetyl-2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2.
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U2 - 10.1021/jm00395a023
DO - 10.1021/jm00395a023
M3 - Article
C2 - 2824777
AN - SCOPUS:0023618704
SN - 0022-2623
VL - 30
SP - 2314
EP - 2316
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 12
ER -