目的合成铂类抗肿瘤新药米铂。方法以K4PtCl4为起始原料，将与亚硝酸钠反应生成的K4Pt(NO2)4溶液，与(1R，2R)-1，2-环己二胺反应生成顺式-二硝基-(1R，2R)-1，2-环己二胺合铂(II)，使用硫酸肼还原NO2-根后将得到的溶液与正十四碳酸钠的正丁醇溶液反应生成米铂。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。结果合成的化合物结构与标题化合物一致，产率约61%。结论本方法为米铂的合成提供了一条新型的工艺路线。
Abstract
OBJECTIVE To synthesize the platinum-based anti-tumor drug miriplatin. METHODS Miriplatin was synthesized from K4PtCl4. K4PtCl4was reacted with sodium nitrite to give the K4Pt(NO2)4 solution which reacted with(1R,2R)-1,2-cyclohexanediamine thus resulting in the key intermediate Pt(C6H14N2)(NO2)2. The key intermediate was subsequently reacted with hydrazine sulfate and sodium myristate in n-butanol to give the target compound. The structure of the target compound was identified by elemental analysis, ESI-MS, FT-IR, 1H-NMR, thermal analysis and specific optical rotation measurement. RESULTS The structure of the synthesized compound was consistent with the title compound, and the yield was about 61%. CONCLUSION This study provides a novel synthesis process for miriplatin.
关键词
化学合成 /
抗肿瘤药物 /
米铂
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Key words
chemical synthesis /
antitumor drug /
miriplatin
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中图分类号：
R97
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参考文献
TAKUJI O, SHUICHI O, TOSHIO N, et al. Phase Ⅱ trial of inra-arterial chemotherapy using a novel lipophilic platinum derivative(SM-11355) in patients with hepatocellular carcinoma. Invest New Drugs, 2004, 22(2):169-176. KISHIMOTO S, NOGUCHI T, YAMAOKA T, et al. In vitro release of SM-11355,cis-platinum(Ⅱ) suspended in Lipiodol. Biol Pharm Bull, 2000, 23(5): 637-640. MAEDA M, SASAKI T. Liposoluble platinum(Ⅱ) complex and preparation thereof: EP, 0193936(B1). 1986-03-05. TANNO N, KISHIMOTO H, NAKATSU M. Fat soluble platinum(ii) complex hydrate:JP, 11315088(A). 1999-11-16. YOKOYAMA T, KISHIMOTO H. Method for preparing platinum complex: JP, 2004083508(A). 2004-03-18. WANG Q K, PU S P, LUAN C F, et al. Synthesis and structural characterization of miriplatin,a platinum-based anti-tumor drug. Chin New Drugs J(中国新药杂志), 2011, 20(17): 1715-1717. WANG Q K, PU S P, ZHU Z B, et al. A new synthetic method and characterization of miriplatin,an antitumor drug. Chin J Med Chem(中国药物化学杂志), 2011, 21(3): 213-215. WANG Q K, PU S P, ZHU Z B, et al. Improved synthesis of miriplatin,an antitumor drug. Chin J Med Chem(中国药物化学杂志), 2012, 22(1): 36-37.
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脚注
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基金
云南省科技计划项目(2010DH021)；昆明市五华区科技计划项目(201037)
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