3'-Hydroxyesorubicin. Synthesis and antitumor activity.
A novel route to 4'-deoxy anthracycline analogues has been developed starting from previously unavailable, optically active 4,6-dideoxy-hex-1-enitol 9. Coupling of daunomycinone (11) or 14-O-tert-butyldimethylsilyladriamycinone (12) with glycosyl chloride 10 in Koenigs-Knorr condition gave mainly alpha anomers, which were successfully deblocked to final 3'-deamino-4'-deoxy-3'-hydroxydaunorubicin (7) and 3'-deamino-3'-hydroxyesorubicin (8). Analogues were evaluated in vitro against P388 and L1210 leukemia and M5076 cells and in vivo against P388 leukemia. Compared with doxorubicin (1), 3'-hydroxyesorubicin (8) showed in vitro similar cytotoxic potential and in vivo higher antitumor activity.
Priebe
W
W
University of Texas M. D. Anderson Cancer Center, Houston 77030.
Neamati
N
N
Perez-Soler
R
R
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D014407:Tumor Cells, Cultured / Q000187:drug effects
C065445:3'-hydroxyesorubicin; D004317:Doxorubicin