Synthesis and antitumor activity of 7-O-(3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl)adriamycinone.
The title compound (7), the 3'-acetoxy-4'-O-acetyl analog of adriamycin (doxorubicin), was synthesized in approximately 50% net yield from daunomycinone by bromination at C-14, glycosylation of the product at O-7 with 3,4-di-O-acetyl-2,6-dideoxy-alpha-L-lyxo-hexopyranosyl chloride, and replacement of the 14-bromo substituent by a hydroxyl group; other possible routes to 7 gave lower yields. The product 7, a non-aminated analog of the anthracycline antibiotics, showed high antitumor activity coupled with low acute toxicity in a broad range of tests in mice.
D000818:Animals; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; C031702:3'-acetoxy-4'-O-acetyldoxorubicin; D004317:Doxorubicin