title: Improved antitumor activity by modification of nogalamycin.
abstract: Nogalamycin, an antitumor antibiotic, has been converted to a series of analogs by removal of the carbomethoxy group at C-10 and replacement of the neutral sugar at C-7 by other groups. Removal of the carbomethoxy group to give disnogamycin (6) followed by acidic alcoholysis gave pairs of isomeric 7-alkoxy compounds differing in configuration at C-7. Treatment of 6 with trifluoroacetic acid followed by nucleophiles gave a series of analogs having substituents at C-7 with a configuration at C-7 opposite to that of nogalamycin. Among the analogs prepared, 7-con-O-methylnogarol (7) is a highly active antitumor agent.
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D006331:Heart Diseases / Q000139:chemically induced; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008968:Molecular Conformation; D009279:Naphthacenes / Q000138:chemical synthesis*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009621:Nogalamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D009279:Naphthacenes; D004317:Doxorubicin; D004247:DNA; D009621:Nogalamycin