Total Synthesis-Enabled Systematic Structure-Activity Relationship Study for Development of a Bioactive Alkyne-Tagged Derivative of Neolaxiflorin L
Total Synthesis-Enabled Systematic Structure-Activity Relationship Study for Development of a Bioactive Alkyne-Tagged Derivative of Neolaxiflorin L
复制标题
新奥拉西弗洛林 L 生物活性炔标记衍生物开发的全合成系统构效关系研究
DOI：
10.1021/acs.joc.9b00748
复制
发表时间：
2019
影响因子：
3.6
通讯作者：
Lee Chi Sing
中科院分区：
文献类型：
--
作者：
Zhang Mengxun;Lee Magnolia Muk Lan;Ye Weijian;Wong Wing Yan;Chan Br;on Dow;Chen Sibao;Zhu Lizhi;Tai William Chi Shing;Lee Chi Sing
Neolaxiflorin L （NL）是一种低丰度的antisodon7,20 -环氧- - kuareoid，在我们之前的研究中被发现是一种很有前途的抗癌候选药物。为了研究其构效关系（SAR），本文开发了两种（±）-NL类似物库的合成途径，包括在相同的7,20-环氧-对-库芳烃骨架中含有不同官能团的类似物和骨架发生变化的类似物。这种全合成SAR的结果成功地产生了具有生物活性的炔标记的NL衍生物，这可能是蛋白质组学研究的有用探针。
Neolaxiflorin L (NL) is a low-abundantIsodon7,20-epoxy-ent-kuarenoid and was found to be a promising anticancer drug candidate in our previous study. In order to study its structure–activity relationship (SAR), a diversity-oriented synthetic route toward two libraries of (±)-NL analogs, including analogs containing different functionalities in the same 7,20-epoxy-ent-kuarene skeleton and analogs with skeletal changes, has been developed. The results of this total synthesis-enabled SAR successfully led to a bioactive alkyne-tagged NL derivative, which could be a useful probe for proteomics studies.