(+)/(-)-Yanhusamides A-C, three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from Corydalis yanhusuo.
10.1016/j.apsb.2022.10.025
- Author:
Lingyan WANG
1
;
Guiyang XIA
1
;
Huan XIA
1
;
Xiaohong WEI
1
;
Yanan WANG
2
;
Sheng LIN
1
Author Information
1. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
(+)/(−)-Yanhusamides A−C;
Analgesic activity;
Anti-inflammatory;
Corydalis yanhusuo;
Hetero-dimeric alkaloids
- From:
Acta Pharmaceutica Sinica B
2023;13(2):754-764
- CountryChina
- Language:English
-
Abstract:
A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids, (+)/(-)-yanhusamides A-C ( 1- 3), featuring an unprecedented 3,8-diazatricylco[5.2.2.02,6]undecane-8,10-diene bridged system. Their structures were exhaustively characterized by X-ray diffraction, comprehensive spectroscopic data analysis, and computational methods. Guided by the hypothetical biosynthetic pathway for 1- 3, a gram-scale biomimetic synthesis of (±)- 1 was achieved in 3 steps using photoenolization/Diels-Alder (PEDA) [4+2] cycloaddition. Compounds 1‒3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages. The in vivo assay showed that oral administration of 30 mg/kg of (±)- 1 attenuated the severity of rat adjuvant-induced arthritis (AIA). Additionally, (±)- 1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.
