Chemoselective Synthesis of Lenalidomide-Based PROTAC Library Using Alkylation Reaction

  • Org Lett. 2019 May 17;21(10):3838-3841. doi: 10.1021/acs.orglett.9b01326.
Xing Qiu  1 ,  Ning Sun  2 ,  Ying Kong  2 ,  Yan Li  2 ,  Xiaobao Yang  2 ,  Biao Jiang  1  2
Affiliations
  • 1. CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry , Chinese Academy of Sciences , 345 Lingling Road , Shanghai 200032 , China.
  • 2. Shanghai Institute for Advanced Immunochemical Studies , ShanghaiTech University , Shanghai 201210 , China.
PMID: 31066567 DOI: 10.1021/acs.orglett.9b01326
Abstract

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.

Products