1. Ligand‐Enabled Pd‐Catalyzed sp3 C−H Macrocyclization: Synthesis and Evaluation of Macrocyclic Sulfonamide for the Treatment of Parkinson's Disease.
- Author
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Bi, Tongyu, Cui, Yunxia, Liu, Shuai, Yu, Haiyue, Qiu, Weirong, Hou, Ke‐Qiang, Zou, Jiaqi, Yu, Zhipeng, Zhang, Feili, Xu, Zhongliang, Zhang, Jian, Xu, Xiaojun, and Yang, Weibo
- Subjects
PARKINSON'S disease ,SULFONAMIDES ,LABORATORY mice ,MEDICAL screening ,ARYLATION - Abstract
The development of simplified synthetic strategy to create structurally and functionally diverse pseudo‐natural macrocyclic molecules is highly appealing but poses a marked challenge. Inspired by natural scaffolds, herein, we describe a practical and concise ligand‐enabled Pd(II)‐catalyzed sp3 C−H alkylation, olefination and arylation macrocyclization, which could offer a novel set of pseudo‐natural macrocyclic sulfonamides. Interestingly, the potential of ligand acceleration in C−H activation is also demonstrated by an unprecedented enantioselective sp3 C−H alkylation macrocyclization. Moreover, a combination of in silico screening and biological evaluation led to the identification of a novel spiro‐grafted macrocyclic sulfonamide 2 a, which showed a promising efficacy for the treatment of Parkinson's disease (PD) in a mouse model through the activation of silent information regulator sirtuin 3 (SIRT3). [ABSTRACT FROM AUTHOR]
- Published
- 2024
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