An efficient synthesis of a doxorubicin-peptide conjugate

An efficient synthesis of the sodium salt of the doxorubicin-peptide conjugate 1, useful for the treatment of prostate cancer is described. The EDC-mediated amide formation between the heptapeptide 4 and doxorubicin (2) as the key step has been extensively studied employing peptide-coupling additives, such as 1-hydroxybenzotriazole (HOBt), l-hydroxy-7-azabenzotriazole (HOAt) and 2-hydroxypyridine N-oxide (HOPO), surprisingly, mixing the additives HOAt and HOPO furnished the best results.