Euphorbia dendroides Latex as a Source of Jatrophane Esters: Isolation, Structural Analysis, Conformational Study, and Anti-CHIKV Activity

J Nat Prod. 2016 Nov 23;79(11):2873-2882. doi: 10.1021/acs.jnatprod.6b00644. Epub 2016 Oct 27.

Abstract

An efficient process was used to isolate six new jatrophane esters, euphodendroidins J (3), K (5), L (6), M, (8), N (10), and O (11), along with seven known diterpenoid esters, namely, euphodendroidins A (4), B (9), E (1), and F (2), jatrophane ester (7), and 3α-hydroxyterracinolides G and B (12 and 13), and terracinolides J and C (14 and 15) from the latex of Euphorbia dendroides. Their 2D structures and relative configurations were established by extensive NMR spectroscopic analysis. The absolute configurations of compounds 1, 11, and 15 were determined by X-ray diffraction analysis. Euphodendroidin F (2) was obtained in 18% yield from the diterpenoid ester-enriched extract after two consecutive flash chromatography steps, making it an interesting starting material for chemical synthesis. Euphodendroidins K and L (5 and 6) showed an unprecedented NMR spectroscopic behavior, which was investigated by variable-temperature NMR experiments and molecular modeling. The structure-conformation relationships study of compounds 1, 5, and 6, using DFT-NMR calculations, indicated the prominent role of the acylation pattern in governing the conformational behavior of these jatrophane esters. The antiviral activity of compounds 1-15 was evaluated against Chikungunya virus (CHIKV) replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antiviral Agents / chemistry
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology
  • Chikungunya Fever / drug therapy
  • Chikungunya virus / drug effects*
  • Crystallography, X-Ray
  • Diterpenes* / chemistry
  • Diterpenes* / isolation & purification
  • Diterpenes* / pharmacology
  • Esters
  • Euphorbia / chemistry*
  • France
  • Latex / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Antiviral Agents
  • Diterpenes
  • Esters
  • Latex
  • jatrophane