2-(4-乙基-3-碘苯基)-2-甲基丙酸合成工艺研究

目的改进2-(4-乙基-3-碘苯基)-2-甲基丙酸的合成工艺。方法以α-溴代异丁酸、氯化亚砜和乙基苯为原料,一锅法合成中间体1-(4-乙基苯基)-2-甲基-2-溴代-1-丙酮,再经1,2-芳基迁移重排、碘代和水解反应制备2-(4-乙基-3-碘苯基)-2-甲基丙酸。结果总收率为75.5%,HPLC纯度为99.8%(面积归一化法)。结论优化后的工艺原料价廉易得,操作简便,成本低廉,适合于工业化生产。

艾乐替尼中间体合成的新工艺

艾乐替尼是一种新型抗癌药,2-(3-碘-4-乙基苯基)-2-甲基丙酸作为其重要的中间体,在合成新药中有着重要的研究价值,广阔的市场和良好的发展前景。以对乙基苯乙酮为起始原料,经过水解、酯化、甲基化、碘代化、水解反应后得到。总收率14.2%,其结构经1H NMR和LC–MS确证。该方法具有原料廉价易得,条件温和,危险性小,操作简单等特点。

Crystal Structure of Carboxypeptidase a Complexed with an Inactivator in a New Crystalline Form

A new crystalline form of carboxypeptidase A (CPA) complexes withan inactivator was obtained by the method of hanging drop vapor diffusion. The inacti-’vator, 2-benzyl-3-iodo-propanoic acid (BIPA ), binds covalently to an active siteresidue Glu-27O of CPA. The complex was crystallized in space group P212121 with a= 48. 8 A, b=66. 9 A, c= 96. 0 A. The complex structure was determined by molecu-lar replacement using the native CPA crystal structure as the search model. The finalcrystallographic residual is 0. 152. Except for the modification of Glu-270, the inactiva-tor exhibits normal binding mode compared with other ligand complexes of CPA. Inthe final different electron density maps (2Fo-Fc, Fo-Fc), the density of the iodo ioncould not be found while the conserved molecule remains coordinated to Zn2+ as in thenative CPA. Comparisons of complex of CPA-BIPA with the native CPA and theCPA/D-Phe complex are presented. The mechanism of inactivation of CPA was dis-cussed.