Adriamycin analogs. Preparation of 9,10-anhydrodaunorubicin, 9,10-anhydroadriamycin, and some related compounds

Abstract
The title compounds, as well as 9,10-anhydro-N-(trifluoroacetyl)adriamycin 14-valerate (9,10-anhydro-AD 32), were prepared starting from daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate (AD 32), respectively. In addition, 9-deoxydaunorubicin and 9-deoxy-AD 32 were obtained by catalytic hydrogenation of the appropriate olefin. All of the products were significantly less active than the parent drugs in inhibiting the growth of CCRF-CEM (human lymphoblastic leukemic) cells in culture. The results suggest the importance of the tertiary alcohol function, as found in the parent compounds at the anthracycline 9 position, in contributing to the expression of biological activity of these agents.