Chemical modification of anthracycline antibiotics IV. Synthesis of new anthracyclines with trisaccharide.
The glycosidation products of O-alpha-L-cinerulosyl-(1 leads to 4)-O-(3-O-acetyl-2-deoxy-alpha-L-fucosyl)-(1 leads to 4)-alpha, beta-L-rhodosamine with aklavinone, daunomycinone, adriamycinone and carminomycinone were synthesized and the resulting products were deacylated, yielding anthracyclines having the trisaccharide. We further synthesized N-monomethyl and N-didemethyl derivatives of daunomycinone trisaccharide by photolysis with sunlight. 3"-O-Acyl derivatives of daunomycinone, carminomycinone and aklavinone glycosides showed a marked antitumor activity against L1210 leukemia in mice with ILS 110, 86 and 86%, respectively, while 3"-O-acetyladriamycinone glycoside was highly toxic with a ILS of 44%.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009279:Naphthacenes / Q000138:chemical synthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D009279:Naphthacenes; D012334:RNA, Neoplasm