QUINOLONE NUCLEOSIDES - 6,7-DIHALO-N-BETA-QUINOLINE-3-CARBOXYLIC AND -GLYCOSYL-1,4-DIHYDRO-4-OXO-QUINOLINE-3-CARBOXYLIC ACIDS AND DERIVATIVES - SYNTHESIS, ANTIMICROBIAL AND ANTIVIRAL ACTIVITY

Reaction of the silylated 6,7-dihaloquinoline bases 10-12 with 1-O-ace tyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (13) gave ethyl nzoyl-beta -D-ribofuranosyl)quinoline-3-carboxylate (14) and the free acids 15 an d 16, respectively, which led on deblocking of the sugar moiety to the free nucleosides 17, 18 and 20, respectively. Treatment of 14 with me thanolic ammonia afforded the amide derivative 19. Ribosylation of 11 with yl-3-azido-3-deoxy-5-p-toluoyl-beta-D-ribofuranose (21) afforded the azido nucleoside 22, which was again converted into the free nucle oside 23. Analogously, reaction of 11 with the chloro deoxyribose deri vative 24 led to a mixture of alpha / beta (2:1) anomers of 25. Debloc king and recrystallization of the product gave mainly the alpha-anomer 26. Compounds 17-19, 23 and 26 were evaluated against Escherichia col i and found inactive. Compound 16-18 and 22 were inactive aganist HIV- 1 (III B) and HIV-2 (ROD) induced cytopathicity in human MT-4 lymphocy te cells.