Fluoro carbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluoro carbocyclic pyrimidine nucleosides including carbocyclic 1- (2-deoxy-2-fluoro-beta-D-arabinofuranosyl) -5-methyluracil and carbocyclic 1- (2-deoxy-2-fluoro-beta-D-arabinofuranosyl) -5-iodouracil
Borthwick, A.D.; Evans, D.N.; Kirk, B.E.; Biggadike, K.; Exall, A.M.; Youds, P.; Roberts, S.M.; Knight, D.J.; Coates, J.A.
Journal of Medicinal Chemistry 33(1): 179-186
1990
ISSN/ISBN: 0022-2623 PMID: 2153201 DOI: 10.1021/jm00163a030
Accession: 007355682
The racemic carbocyclic 2'-fluoroarabinosyl pyrimidine nucleosides, 8, 9 (C-FIAU), 12, and 13 (C-FMAU) and the 2'-fluororibosyl pyrimidine nucleosides 17, 20, and 21 were prepared from their respective protected 2'-fluoro amino diols 5 and 14. The carbocyclic 2',2'-difluorothymidine analogue 27 was obtained from the protected difluoro amino diol 24 which was prepared from the ketone 23 and (diethylamino)sulfur trifluoride (DAST). The chiral carbocyclic 2'-deoxy-6'-fluorouridines 33, 34, 38, and 39 were synthesized from the protected 6-fluoro amino diols 30 and 36, which were prepared by reduction of the azides 28 and 35. C-FMAU (13) and C-FIAU (9) were active in vitro against HSV-1 with ID50 values of 4.4 and 11 .mu.g/mL, respectively, but they were inactive against HSV-2. The cytidine analogues 12 and 20 displayed modest activity in vitro against HSV-1 and HSV-2 but were inactive against human influenza A virus.