Ha Jin Joo, Han Hye Jee, Kim Hee Eun, Jin Jong Sung, Jeong Euh Duck, Hyun Myung Ho
Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 609-735, Republic of Korea.
Division of High Technology Materials Research, Busan Center, Korea Basic Science Institute (KBSI), Busan 618-230, Republic of Korea.
J Pharm Biomed Anal. 2014 Nov;100:88-93. doi: 10.1016/j.jpba.2014.07.029. Epub 2014 Aug 2.
As an effort to develop improved ligand exchange chiral stationary phases (CSPs) for the resolution of chiral drugs, the residual silanol groups on the silica surface of a CSP based on sodium N-[(S)-1-hydroxymethyl-3-methylbutyl]-N-undecylaminoacetate, a (S)-leucinol derivative, were protected with n-octyl groups. The residual silanol group-protected CSP was applied to the resolution of proton pump inhibitors (PPIs) such as omeprazole, pantoprazole, lansoprazole and rabeprazole. The resolution of PPIs on the residual silanol group-protected CSP was excellent with the separation factors (α) in the range of 4.32-6.42 and the resolution factors (RS) in the range of 6.70-7.15. The improved chiral recognition ability of the residual silanol group-protected CSP was rationalized to be originated from the protection of the non-enantioselective interaction sites on the silica surface and the improved lipophilicity of the stationary phase.
作为开发用于拆分手性药物的改进型配体交换手性固定相（CSPs）的一项工作，基于N-[(S)-1-羟甲基-3-甲基丁基]-N-十一烷基氨基乙酸钠（一种(S)-亮氨醇衍生物）的CSP的硅胶表面上的残留硅醇基团用正辛基进行了保护。将残留硅醇基团保护的CSP应用于拆分质子泵抑制剂（PPIs），如奥美拉唑、泮托拉唑、兰索拉唑和雷贝拉唑。PPIs在残留硅醇基团保护的CSP上的拆分效果极佳，分离因子（α）在4.32 - 6.42范围内，分离度因子（RS）在6.70 - 7.15范围内。残留硅醇基团保护的CSP手性识别能力的提高被认为源于硅胶表面非对映选择性相互作用位点的保护以及固定相亲脂性的提高。
