首页 | 本学科首页   官方微博 | 高级检索  
     


Simplifying Access to Targeted Protein Degraders via Nickel Electrocatalytic Cross-Coupling
Authors:Philipp Neigenfind  Dr. Luca Massaro  Dr. Áron Péter  Dr. Andrew P. Degnan  Dr. Megan A. Emmanuel  Dr. Martins S. Oderinde  Dr. Chi He  Dr. David Peters  Tamara El-Hayek Ewing  Dr. Yu Kawamata  Prof. Dr. Phil S. Baran
Affiliation:1. Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, 92037 La Jolla, CA, United States

These authors contributed equally to this work;2. Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, 92037 La Jolla, CA, United States

Department of Chemistry, KTH Royal Institute of Technology, Teknikringen 30, S-10044 Stockholm, Sweden

These authors contributed equally to this work;3. Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, 92037 La Jolla, CA, United States;4. Small Molecule Drug Discovery, Bristol Myers Squibb Research & Early Development, Route 206 & Province Line Road, 08543 Princeton, NJ, United States;5. Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, 08901 New Brunswick, NJ, United States;6. Small Molecule Drug Discovery, Bristol Myers Squibb Research & Early Development, 10300 Campus Point Drive, 92121 San Diego, CA, United States.

Abstract:C−C linked glutarimide-containing structures with direct utility in the preparation of cereblon-based degraders (PROTACs, CELMoDs) can be assessed in a single step from inexpensive, commercial α-bromoglutarimide through a unique Brønsted-acid assisted Ni-electrocatalytic approach. The reaction tolerates a broad array of functional groups that are historically problematic and can be applied to the simplified synthesis of dozens of known compounds that have only been procured through laborious, wasteful, multi-step sequences. The reaction is scalable in both batch and flow and features a trivial procedure wherein the most time-consuming aspect of reaction setup is weighing out the starting materials.
Keywords:Electrochemistry  Proteins  Cross-Coupling  Nickel Catalysis  Radicals
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号