loading page

Unprecedented Nor-seco-diterpene Lactones Inhibited Osteogenic Differentiation of Valve Interstitial Cells
  • +6
  • Jiangchun Wei,
  • Xingpiao Jin,
  • Pingping Fan,
  • Xinping Li,
  • Xuanluan Chen,
  • Wanxia Zhai,
  • Yonghui Zhang,
  • Zhengxi Hu,
  • Zhengzhi Wu
Jiangchun Wei
Huazhong University of Science and Technology Tongji Medical College
Author Profile
Xingpiao Jin
Shenzhen Second People's Hospital
Author Profile
Pingping Fan
Huazhong University of Science and Technology Tongji Medical College
Author Profile
Xinping Li
Shenzhen Second People's Hospital
Author Profile
Xuanluan Chen
Shenzhen Second People's Hospital
Author Profile
Wanxia Zhai
Shenzhen Second People's Hospital
Author Profile
Yonghui Zhang
Huazhong University of Science and Technology

Corresponding Author:[email protected]

Author Profile
Zhengxi Hu
Huazhong University of Science and Technology Tongji Medical College
Author Profile
Zhengzhi Wu
Shenzhen Second People's Hospital
Author Profile

Abstract

The first examples of diterpene lactones with an unusual 2-nor-tetrahydro-2H-pyran-2-one nucleus, eufislactones A (1) and B (2), were isolated from the roots of Euphorbia fischeriana, together with a new (3) and fifteen known biosynthetic congeners (4–18). Compound 1 possesses an unprecedented 2,3-seco-2-nor-ent-atisane diterpenoid skeleton, and 2 features a new 2,3-seco-2-nor-ent-isopimarane diterpenoid core. Their structures incorporating absolute configurations were elucidated via the comprehensive spectroscopic analyses, quantum chemical calculations, electronic circular dichroism (ECD) calculations, and sin-gle-crystal X-ray diffraction analyses. Biogenetically, this compound was constructed by the plausible monomeric precursor, ent-atis-16-ene-3,14-dione (6) and ent-isopimara-8(14),15-dien-3-one (17), via key Baeyer-Villiger oxidation, decarboxylation, and recyclization to form an unique 2-nor-tetrahydro-2H-pyran-2-one core. Our bioassays have revealed that eufislactone A (EFA, 1) dis-played significant inhibitory effect on the osteogenic differentiation of human valvular interstitial cells (VICs), highlighting its poten-tial as a preventive agent against the progression of human calcific aortic valve disease (CAVD).