We have initiated a broad synthetic program to investigate the synthesis of selected precious metal complexes (e.g., Pt, Rh, Ir, Ru) using a microwave-assisted approach. We present here a summary of our work on the microwave-assisted synthesis of Cisplatin, a potent anticancer drug known globally1.The goals of our studies were (1) to explore the use of microwave technology to synthesize Cisplatin and (2) to develop a rapid, microscale synthesis of pure Cisplatin in order to facilitate the incorporation of the short-lived radioisotope, 195mPt (t1/2 = 4.1d), and thereby maximize the useful life of radiolabeled Cisplatin in biological studies.Initial syntheses were modeled after the conditions of the Lebedinskii-Golovnya method2 and under exposure to microwave radiation (2450 MHz). K2PtCl4 (0.05 to 0.2 millimoles) was the starting material in all reactions. Reaction parameters (scale of synthesis, reaction time, temperature, ratios of reactant concentrations relative to Pt(II) & various NH4+ salts) were varied systematically while under the influence of the microwave radiation to achieve the highest yields and purity of cisplatin.The optimized procedure permits yields of > 40% of highly pure Cisplatin on a scale of 50-200 mmol. While the synthesis requires a microwave irradiation time of 15 min at 100�C at millimolar ratios of NH4+/ K2PtCl4 = 4, and KCl/ K2PtCl4 = 2, the purification of the crude product requires an additional hour. Purification is achieved by fractionating the major impurity, [Pt(NH3)3Cl][ Pt(NH3)Cl3], using K2PtCl4 to form the insoluble salt, [Pt(NH3)3Cl]2[ PtCl4]. Reaction products were evaluated by 1H-NMR, HPLC, and UV-Vis spectroscopy. While the optimal yield is less than that obtained using the Dhara method, the preparation time is shorter3. References   1. B. Rosenberg, L. VanCamp, T. Krigas, Nature, 1965 , 205, 698.2. V. V. Lebedinskii, V. A. Golovnya, Izv. Sektora Platiny AN SSSR, 1945,  20, 95.3  S. C. Dhara, Indian J. Chemistry, 1970 , 8, 193.

Microwave-assisted synthesis of cisplatin

247th National Meeting (2014)

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