Synthesis of gem-bisphosphonic doxorubicin conjugates

Four gem-bisphosphonic doxorubicin conjugates are prepared by coupling the amino function of doxorubicin with the activated carboxylic functions of 3,3-bis(diethylphosphono)propanoic acid 2, 4,4-bis(diethylphosphono)butanoic acid 3, and (R + S)-N-(9-fluorenylmethyloxycarbonyl)-2-amino-4,4-bis(diethylphosphono)butanoic acid 6. The last compound provides two epimers which are separated by chromatography. Sodium salts are obtained. These original products participate in a biological study about a delivery-targeting concept of antineoplastic agents in bone cancer therapy, with the assistance of gem-bisphosphonic building blocks.