抗肿瘤药米铂的合成工艺改进

Improved synthesis of miriplatin,an antitumor drug

目的改进抗肿瘤药米铂的合成工艺。方法以顺式-二碘-(1R,2R)-1,2-环己二胺合铂(Ⅱ)为起始原料,将顺式-二碘-(1R,2R)-1,2-环己二胺合铂(Ⅱ)与硝酸银水解合成含有硝酸根的水合物溶液,然后与阴离子树脂交换生成顺式-二羟基-(1R,2R)-1,2-环己二胺合铂(Ⅱ)的水溶液,再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、热分析和比旋光度对其结构进行表征。结果与结论合成的化合物结构与标题化合物一致,收率约75%。该方法便于操作,收率高。

Miriplatin （1）, a novel lipophilic platinum complex, had been developed to treat hepatoceUular carcinoma. An improved synthetic route was designed and used to prepare the target compound. The intermediate Pt（C6a14N2） （H2O）2 （NO3）2 solution was synthesized from Pt （C6H14N2 ）（I） 2 and AgNO3, and it was treated with the anion exchange resin to give the key intermediate Pt（ C6H14N2 ） （OH） 2 （2）. The key intermediate 2 was subsequently reacted with CH3（ CH2 ）12COOH in n-butanol to give target compound with satisfied yield 75 % （based on Pt（ C6H14N2 ）I2 ）. The structure of the target compound was identified by elemental analysis, ESI-MS, FT-IR, 1^H-NMR, thermal analysis and specific rotatory power, and the structure was consistent with the target compound.