title: Microwave-assisted synthesis of the anticancer drug cisplatin, cis-[Pt(NH3)2Cl2].
abstract: A microwave-assisted synthesis of cisplatin, cis-[Pt(NH3)2Cl2], has been developed and optimized on both a 0.2 and 0.05 millimolar scale. The optimized synthetic procedure was modeled after the Lebedinskii-Golovnya method and is suitable for incorporating the radionuclide, (195m)Pt, into cisplatin for biological studies. Highest yields (47%) and purity are obtained using a K2PtCl4 : NH4OAc : KCl molar ratio of 1 : 4 : 2 at a temperature of 100 °C. The entire synthesis and purification procedure requires approximately 80 min. At a reaction temperature of 150 °C, the trans isomer is the exclusive product, suggesting that complexes of the general form, trans-[Pt(RNH2)2Cl2], can be synthesized directly from K2PtCl4 using [RNH3]OAc (R = alkyl or aryl moieties) via a microwave process. Two novel separation procedures have been developed which efficiently remove the major impurity (1 : 1 Magnus-type salt) from the crude reaction product, yielding a product of purity comparable to that obtained by the Dhara method and suitable for biological studies. These procedures are applicable to both the micro- and macro-scale of synthesis. The question of whether this microwave-assisted synthesis of cisplatin will be a preferred method for incorporating (195m)Pt into cisplatin is yet to be determined.
authors.affiliation: Department of Chemistry, Eastern Michigan University, Ypsilanti, MI 48197, USA. jhoesche@emich.edu.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Petruzzella
authors.forename: Cristian V
authors.initials: CV
authors.lastname: Chirosca
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Heidenga
authors.forename: James D
authors.initials: JD
authors.lastname: Hoeschele
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002945:Cisplatin / Q000138:chemical synthesis*; D008872:Microwaves; D009944:Organoplatinum Compounds / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D002945:Cisplatin