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

Author:
Esposito, Mélissa, Nothias, Louis-Félix, Nedev, Hirsto, Gallard, Jean-François, Leyssen, Pieter, Retailleau, Pascal, Costa, Jean, Roussi, Fanny, Iorga, Bogdan I., Paolini, Julien, Litaudon, Marc
Source:
Journal of natural products 2016 v.79 no.11 pp. 2873-2882
ISSN:
1520-6025
Subject:
Chikungunya virus, Euphorbia, X-ray diffraction, acylation, antiviral properties, chromatography, diterpenoids, esters, latex, molecular models, nuclear magnetic resonance spectroscopy, spectral analysis, synthesis
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.
Agid:
5590307