Highly Oxygenated Dimeric Grayanane Diterpenoids as Analgesics:TRPV1 and TRPA1 Dual Antagonists from Rhododendron molle  

作　　者：Lang Huang Guijuan Zheng Yuanyuan Feng Pengfei Jin Biao Gao Hanqi Zhang Xiaomin Ma Junfei Zhou Guangmin Yao 

机构地区：[1]Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation,School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,430030 China [2]State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany,Chinese Academy of Sciences,Kunming,Yunnan,650201 China [3]Laboratory of Xinjiang Native Medicinal and Edible Plant Resource Chemistry,College of Chemistry and Environmental Science,Kashi University,Kashgar,Xinjiang,844007 China

出　　处：《Chinese Journal of Chemistry》2022年第19期2285-2295,共11页中国化学（英文版）

基　　金：This work was supported by the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2022-KF08);the Fund of Laboratory of Xinjiang Native Medicinal and Edible Plant Resource Chemistry(KSUZDSYS202101);the National Natural Science Foundation of China(22107033 and U1703109);the Traditional Chinese Medicine of Hubei Provincial Health Commission(ZY2021M056);the China Postdoctoral Science Foundation(2021M691152)。

摘　　要：Six highly oxygenated dimeric grayanane diterpenoids(1—6)including three new ones,bismollethers A—C(1—3),were isolated from the flowers of Rhododendron molle collected at Qichun,Hubei,China.The structures and relative configurations of 1—6 were determined by comprehensive spectroscopic data analysis and 13C NMR calculation with DP4+analysis.The absolute configurations of bismollethers A—C(1—3)and birhodomollein B(5)were indubitably assigned by single-crystal X-ray diffraction analysis,revealing the head-to-tail linking manner of diterpenoid monomers.Bismollether A(1)is a caged dimeric grayanane diterpenoid linked through two oxygen-bridges of C-2−O−C-14′and C-14−O−C-2′,featuring a unique 1,8-dioxacyclotetradecane motif.The plausible biosynthesis pathways of 1—6 are proposed.All the isolates displayed significant analgesic activities and their structure-activity relationships were discussed.Grayanane diterpenoid dimers were found to be TRPV1 and TRPA1 dual antagonists,and docking studies provide a structural basis to design potent analgesics.

关 键 词：Biological activity Dimeric grayanane diterpenoids Natural products Rhododendron molle(Ericaceae) Structure elucidation 

分 类 号：O62[理学—有机化学]