Ligand-Enabled Pd-Catalyzed sp3 CâH Macrocyclization: Synthesis and Evaluation of Macrocyclic Sulfonamide for the Treatment of Parkinson's Disease.
Angew Chem Int Ed Engl
; : e202412296, 2024 Jul 30.
Article
in En
| MEDLINE
| ID: mdl-39078406
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)-catalysed sp3 CâH alkylation, olefination and arylation macrocyclization, which could offer a novel set of pseudo-natural macrocyclic sulfonamides. Interestingly, the potential of ligand acceleration in CâH activation is also demonstrated by an unprecedented enantioselective sp3 CâH alkylation macrocyclization. Moreover, a combination of in silico screening and biological evaluation led to the identification of a novel spiro-grafted macrocyclic sulfonamide 2a, 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).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Germany