2. Academic Validation
  3. Unusual ent-Labdane Diterpenoid Dimers and their Selective Activation of TRPV Channels

Unusual ent-Labdane Diterpenoid Dimers and their Selective Activation of TRPV Channels

  • J Org Chem. 2019 Nov 1;84(21):13595-13603. doi: 10.1021/acs.joc.9b01864.
Suyu Gao 1,  Dun Wang 1,  Hao Chai 2 3,  Jiamin Xu 1,  Tianyu Li 2 3,  Yingxue Niu 1,  Xinxin Chen 1,  Feng Qiu 4,  Yang Li 2 3,  Hua Li 1 5,  Lixia Chen 1
Affiliations

Affiliations

  • 1 Wuya College of Innovation, School of Pharmaceutical Engineering, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
  • 2 State Key Laboratory of Drug Research and Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica , Chinese Academy of Sciences , Shanghai 201203 , China.
  • 3 University of Chinese Academy of Sciences , No. 19A Yuquan Road , Beijing 100049 , China.
  • 4 School of Chinese Materia Medica and Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , Tianjin 300193 , China.
  • 5 School of Pharmacy, Tongji Medical College , Huazhong University of Science and Technology , Wuhan 430030 , China.
PMID: 31549831 DOI: 10.1021/acs.joc.9b01864
Abstract

Five unusual dimers of ent-labdane Diterpenoids (1-5) were isolated and identified from Andrographis paniculata, a famous medicinal plant. Bisandrographolide E (1) represents the first example of a labdane dimer possessing an unprecedent tricyclic system that comprised a spiroketal moiety fused with a ketal-γ-lactone unit in its skeleton. Its biosynthetically related intermediates, all four stereoisomers at C-12 and C-15', bisandrographolides F (2, a new compound) and A-C (3-5), were obtained at the same time. The steric configurations of the newly formed asymmetric carbons in 1-5 were first solved by single-crystal X-ray diffraction of the diacetone derivatives of 2-4 and ECD and NMR calculations of 1. More importantly, bisandrographolides 1-5, with different chemical structures or absolute configurations at C-12 and C-15', selectively activated different TRPV1-4 channels and protected cardiomyocytes from hypoxia-reoxygenation injury. Among them, 5 with 12R/15'S configuration activated TRPV1 most effectively and displayed the best cardiomyocyte protection.

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