手性流动相添加剂法拆分西那卡塞原料及中间体

Enantiomeric Separation of Raw Material and Intermediate of Cinacalcet Using Chiral Mobile Phase Additives

以自制1-萘万古霉素(Na-VAN)为手性固定相(CSP),D-酒石酸(D-Tar)、L-酒石酸二乙酯(L-TADE)、D-酒石酸二乙酯(D-TADE)分别为手性流动相添加剂(CMPA),建立了西那卡塞原料1-(1-萘基)乙胺(化合物1)及西那卡塞中间体(化合物2)的高效液相色谱手性拆分方法。考察了流动相中醇类改性剂、CMPA对对映体分离的影响,初步探讨了手性识别机理。以Na-VAN为CSP,正相模式下,添加不同种类的CMPA,化合物1、化合物2均可获得一定程度的分离,其中以D-TADE为CMPA时,化合物1、化合物2获得最佳分离。结果表明,醇的分子体积、CMPA的立体构型均对手性分离有影响。

An HPLC method was established for the chiral separation of cinacalcet raw material,1-（1-naphthyl） ethylamine（compound 1） and intermediate of cinacalcet（compound 2）,by using selfmade 1-naphthalene vancomycin as chiral stationary phase（Na-VAN CSP）,and D-tartaric acid（DTar）,L-tartaric acid diethyl ester（L-TADE） and D-tartaric acid diethyl ester（D-TADE） as chiral mobile phase additives（CMPA）,respectively. The influences of alcohol modifiers and CMPA types were studied. The mechanism of enantioseparation was also discussed. On Na-VAN CSP,compound 1 and 2 got certain degree of enantioseparation with different CMPA under normal phase conditions. When D-TADE was used as CMPA,the optimal enantioseparation for both compound 1 and 2was obtained. The results showed that the size of alcohol modifier and the three dimensional configuration of CMPA played an important role in the enantioseparation.