Bestatin衍生物的立体选择性合成及活性研究  

The stereoselective synthesis and primary activity assay of Bestatin′s derivatives

作　　者：牟佳佳[1] 张涛 徐文方[1] 

机构地区：[1]山东大学药学院药物化学研究所,山东济南250012 [2]上海药明康德新药开发有限公司,上海200131

出　　处：《中国药物化学杂志》2009年第6期401-406,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家高技术研究发展计划项目(2007AA02Z314);国家自然科学基金重大专项研究计划课题(90713041);国家自然科学基金项目(30772654);教育部博士点基金项目(20060422029)

摘　　要：目的立体选择性地合成Bestatin衍生物。方法利用普通的硅胶加压柱联合L-氨基酸甲酯盐酸盐作为手性衍生化试剂将具有同一结构式的4个外消旋混合物进行了分离。结果成功地合成并分离了Bestatin衍生物12个,体外抑酶活性表明12a、13a、15a等化合物有较高的抑制氨肽酶N(APN)的活性。结论该实验的方法能立体选择性地合成Bestatin的衍生物,但化合物的绝对构型还有待确定。Aim The derivatives of Bestatin were synthesized stereoselectively. Methods Combined normal silica pressure column with L-aa-OCH3· HCI as chiral pool, four racemic mixtures were synthesized and separated. Results 12 Bestatin＇s derivatives were synthesized and separated successfully, and activity assay in vitro showed that compounds 12a,13a and 15a had high inhibitory activities against APN. Conclusion The method we used could stereoselectively synthesize Bestatin＇s derivatives. The determination of the absolute configurations of our target compounds is under way.

关 键 词：立体选择性合成 氨肽酶N BESTATIN 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]