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 a 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.
ASJC Scopus subject areas
- Drug Discovery