利用烷基化反应对来那度胺基PROTAC文库进行化学选择性合成。
Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction.
作者信息
Qiu Xing, Sun Ning, Kong Ying, Li Yan, Yang Xiaobao, Jiang Biao
机构信息
CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry , Chinese Academy of Sciences , 345 Lingling Road , Shanghai 200032 , China.
Shanghai Institute for Advanced Immunochemical Studies , ShanghaiTech University , Shanghai 201210 , China.
出版信息
Org Lett. 2019 May 17;21(10):3838-3841. doi: 10.1021/acs.orglett.9b01326. Epub 2019 May 8.
An organic base-promoted chemoselective alkylation of lenalidomide with different halides was developed, which offers a novel approach to a highly functionalized lenalidomide-based PROTAC library under mild reaction conditions. DIPEA was found to act as an efficient base to trigger facile generation of arylamine alkylation products compared with inorganic bases. This library was successfully applied to BET PROTAC, which not only degraded BET protein but also effectively inhibited cancer cell proliferation.
开发了一种有机碱促进的来那度胺与不同卤化物的化学选择性烷基化反应，该反应在温和的反应条件下为构建高度官能化的基于来那度胺的PROTAC文库提供了一种新方法。与无机碱相比，发现二异丙基乙胺（DIPEA）作为一种有效的碱可引发芳胺烷基化产物的轻松生成。该文库已成功应用于BET PROTAC，它不仅能降解BET蛋白，还能有效抑制癌细胞增殖。
Zotero 插件