1. Ligand-Enabled Pd-Catalyzed sp 3 C-H Macrocyclization: Synthesis and Evaluation of Macrocyclic Sulfonamide for the Treatment of Parkinson's Disease.
- Author
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Bi T, Cui Y, Liu S, Yu H, Qiu W, Hou KQ, Zou J, Yu Z, Zhang F, Xu Z, Zhang J, Xu X, and Yang W
- Subjects
- Catalysis, Ligands, Cyclization, Animals, Mice, Molecular Structure, Humans, Sirtuin 3 metabolism, Sirtuin 3 antagonists & inhibitors, Palladium chemistry, Sulfonamides chemistry, Sulfonamides chemical synthesis, Parkinson Disease drug therapy, Macrocyclic Compounds chemistry, Macrocyclic Compounds chemical synthesis, Macrocyclic Compounds pharmacology
- 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 sp
3 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)., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
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