Studies on the Oral Anticancer Drug JM-216:  Synthesis and Characterization of Isomers and Related Complexes

The complex cis,trans,cis-[PtCl2(OAc)2NH3(c-C6H11NH2)] (JM-216) is currently undergoing clinical evaluation as an antitumor agent. In support of characterization and analysis of this complex a study of its isomers and other complexes [PtCl m (OAc)(4 - m )NH3(c-C6H11NH2)] (m = 0−4) has been undertaken. The complexes have been obtained by a variety of synthetic routes which now extend the scope for the preparation of platinum(IV) antitumor complexes. As platinum(IV) complexes are very stable to substitution in the absence of catalysis, use has been made of both light and base catalysis to promote substitution. Oxidative addition to platinum(II) using hypervalent iodine reagents has also been used. The stereochemistry of the complexes has been confirmed by spectroscopic studies, primarily NMR including natural abundance 15N NMR spectroscopy.