Synthesis and biological activity of certain derivatives of oxazinomycin and related oxadiazole nucleosides.
Oxazinomycin was converted into 2',3',5'-tri-O-acetyloxazinomycin (2) and 2',3'-O-isopropylideneoxazinomycin (3), respectively. Compound 3 was iodinated and reduced to provide 5'-deoxy-2',3'-O-isopropylideneoxazinomycin (5) which, after acid hydrolysis, provided 5'-deoxyoxazinomycin (6). Alternatively, the iodination of oxazinomycin followed by catalytic hydrogenation also provided 6. Oxazinomycin was treated with 2-acetoxybenzoyl chloride to provide 3'-O-acetyl-2'-chloro-2'-deoxyoxazinomycin (8) which, after reduction with tributyltin hydride, provided 3'-O-acetyl-2'-deoxyoxazinomycin (9). Oxazinomycin was also converted into oxazinomycin 5'-phosphate (10) and into O4,2'-anhydrooxazinomycin (11). 1,2,4-Oxadiazole-3,5-dione (12) was glycosylated to provide 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1,2,4-oxadiazole-3,5-dione (13) which, after deacetylation, provided 2-beta-D-ribofuranosyl-1,2,4-oxadiazole-3,5-dione (14). Similarly, 12 provided 2-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-3,5-dione (17); 14 was also converted into the corresponding 2',3'-O-isopropylidene derivative 15. Compound 14 showed significant antiviral activity against herpes simplex virus type 1, in vitro.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D007939:Leukemia L1210 / Q000188:drug therapy; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D010069:Oxadiazoles; D012263:Ribonucleosides; C002363:minimycin; D014529:Uridine