FLUORO CARBOCYCLIC NUCLEOSIDES - SYNTHESIS AND ANTIVIRAL ACTIVITY OF 2'-FLUORO 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

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 ID50values of 4.4 and 11 µg/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. © 1990, American Chemical Society. All rights reserved.