5-Deoxy,12-deoxy,5,12-bisdeoxy, and 4,5,12-trisdeoxy anthracyclines: Synthesis of new analogues of daunorubicin and doxorubicin by controlled deoxygenation of the C-ring

Hydrogenation of the anthracyclines daunorubicin (1) and doxorubicin (2) ga ve selective deoxygenation at position 5. Hydride reduction of (1) and (2) gave complementary regiocontrol, leading to 12-deoxygenation or 5,12-bis-de oxygenation. This chemistry allows retention of the 7-glycoside and the sid e-chain carbonyl groups. It has led to new anthracycline families possessin g all of the stereochemical and most of the spatial characteristics of the parent compounds (1) and (2). These are typified by 5-deoxy (12), (15); 12- deoxy (22), (23); 5,12-bisdeoxy (34), (35); and 4,5,12-trisdeoxy systems (3 6). All possess high anticancer activity.