Initial Biotransformations of Daunorubicin to Aglycones by Rat Liver Microsomes¹

Anaerobic incubations of rat liver microsomes convert daunorubicin into at least six or seven aglycones in the presence of reduced nicotinamide adenine dinucleotide phosphate or a reduced nicotinamide adenine dinucleotide phosphate-generating system. The partial identification of some of the aglycones is based on cochromatographs of chemically synthesized derivatives by isocratic high-pressure liquid chromatography. The first major reaction is the reductive cleavage of daunorubicin to 7-deoxydaunorubicin aglycone which is converted to another product that cochromatographs with 7-deoxydaunorubicinol aglycone. The reaction follows first-order kinetics in a linear sequential pathway. Formation of 7-hydroxydaunorubicin aglycone is also identified as a product. Other reaction products are not yet identified.