通过膦催化的[4 + 1]环化反应构建3-氧代-3H-螺[苯并呋喃-2,1'-环戊烷]羧酸衍生物及其抗纤维化的生物学评价

Construction of 3-oxo-3H-spiro[benzofuran-2,1'-cyclopentane] carboxylic acid derivatives via phosphine-catalyzed [4 + 1] annulations and their biological evaluation against fibrosis.

作者信息

Li Sheng-Hong, Lu Feng-Yi, Katta Muralikrishna, Liu Yun-Yun, Huang Danling, Cheng Yong-Xian

机构信息

Institute for Inheritance-Based Innovation of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, School of Pharmacy, Shenzhen University Medical School, Shenzhen 518060, PR China.

出版信息

Bioorg Med Chem. 2025 Jul 1;124:118192. doi: 10.1016/j.bmc.2025.118192. Epub 2025 Apr 9.

DOI:10.1016/j.bmc.2025.118192

PMID:40252564

Abstract

A novel phosphine-catalyzed [4 + 1] cyclization reaction was developed to construct the 3-oxo-3H-spiro[benzofuran-2,1'-cyclopentane] scaffold. Utilizing this innovative method, twenty diverse 3-oxo-3H-spiro[benzofuran-2,1'-cyclopentane] carboxylic acid derivatives were synthesized and evaluated for their anti-fibrotic activities. Compound L10-P1 possessed potential anti-fibrotic activity by inhibiting the expression of fibronectin, collagen I, and α-SMA. This study presents a new synthetic route for 3H-spiro[benzofuran-2,1'-cyclopentan]-3-one derivatives, contributing valuable insights into the chemical and biological diversity of these compounds.

摘要

开发了一种新型的膦催化[4 + 1]环化反应，用于构建3-氧代-3H-螺[苯并呋喃-2,1'-环戊烷]骨架。利用这种创新方法，合成了20种不同的3-氧代-3H-螺[苯并呋喃-2,1'-环戊烷]羧酸衍生物，并对其抗纤维化活性进行了评估。化合物L10-P1通过抑制纤连蛋白、I型胶原蛋白和α-SMA的表达而具有潜在的抗纤维化活性。本研究为3H-螺[苯并呋喃-2,1'-环戊烷]-3-酮衍生物提供了一条新的合成路线，为这些化合物的化学和生物多样性提供了有价值的见解。