Synthesis and antitumor activity of 2'-bromo- and 2'-chloro-3'-acetoxy-3'-deaminodaunorubicin analogs.
Bromination of 3,4-di-O-acetyl-L-rhamnal (7) and subsequent glycosidic coupling under Koenigs-Knorr conditions with daunomycinone gave a mixture of three compounds having the beta-L-gluco (10), alpha-L-gluco (11), and alpha-L-manno (12) configurations. Analogous bromination of 3,4-di-O-acetyl-L-fucal (13) followed by coupling with daunomycinone gave a mixture of three glycosides having the beta-L-galacto (16), alpha-L-galacto (17), and alpha-L-talo (18) configurations. Chlorination of 7 and coupling with daunomycinone in the presence of silver triflate gave products having the alpha-L-gluco (21) and alpha-L-manno (22) configurations, whereas 13, under similar conditions, gave only one stereoisomeric product, that having the alpha-L-galacto (24) configuration. Compounds 12 and 22 showed high in vivo activity in the P-388 lymphocytic leukemia assay.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; D003630:Daunorubicin