抗肿瘤药米铂的一种新合成方法及结构表征

A new synthetic method and characterization of miriplatin,an antitumor drug

目的合成抗肿瘤新药米铂。方法以顺式-(1R,2R)-1,2-环己二胺-二碘合铂(Ⅱ)为起始原料,先将顺式-(1R2,R)-12,-环己二胺-二碘合铂(Ⅱ)与硫酸银水解成含有硫酸根的水合物溶液,然后与八水氢氧化钡反应生成顺式-(1R2,R)-12,-环己二胺-二羟基合铂(Ⅱ)的水溶液,最后与正十四碳酸的正丁醇溶液反应合成米铂。采用元素分析、质谱、红外光谱、核磁共振氢谱和热分析对其结构进行表征。结果与结论合成的化合物结构与标题化合物一致,收率约68%。该方法便于操作,收率高,可做进一步研究。

Miriplatin（1）,a novel lipophilic platinum complex has been developed to treat hepatocellular carcinoma.A new synthetic route was designed and used to prepare the target compound.The key intermediate Pt（C6H14N2）（OH）2（2）,synthesized from Pt（C6H14N2）I2 with AgNO3 and Ba（OH）2·8H2O,was subsequently reacted with CH3（CH2）12COOH in n-butanol to give target compound with satisfied yield 68%（based on Pt（C6H14N2）I2）.The structure of the target compound was identified by elemental analysis.ESI-MS,FT-IR,1H-NMR and thermal analysis.And the structure was consistent with the target compound.Compared with reported methods,the new starting compound Pt（C6H14N2）I2 replacing the Pt（C6H14N2）Cl2 is convenient for controlling the Ag＋,and using n-butanol-H2O as the reaction medium can achieve a desirable reaction rate,however a large amount of CH3（CH2）12COONa in the product was not easy to be removed.In addition,using n-butanol is less harmful than chloroform to human body.