Improved synthesis and evaluation of 17-substituted aminoalkylgeldanamycin derivatives applicable to drug delivery systems

The 17-methoxy group of geldanamycin was substituted with 1,3-diaminopropane and 1,3-diamino-2-hydroxypropane to introduce a primary amino group useful for conjugation with targeting moieties and drug carriers. We have developed a procedure that has provided improved yield and reproducibility of the syntheses. Both geldanamycin derivatives demonstrated antiproliferative activity towards the human ovarian carcinoma cell line, A2780.