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

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.

Jatrophane and rearranged jatrophane-type diterpenes: biogenesis, structure, isolation, biological activity and SARs (1984–2019)

“…It is worth mentioning that the flexibility of the twelve-membered ring can adopt two main conformations: endo-and exo-type depending on the spatial orientation of the 6,17 exo-methylene group (Appendino et al 1998;Jakupovic et al 1998b, c;Marco et al 1998). It is also reported that the conformational option depends on the acylation pattern on the jatrophane core (Corea et al 2005a;Esposito et al 2016;Günther et al 1998). Diagnostic spectral features to discriminate between the two conformations are the 3 J 4,5 value and spatial close NOESY correlations (Appendino et al 1998;Corea et al 2005a;Jakupovic et al 1998c).…”

“…Furthermore, the C-8 substitution influences the activity of jatrophanes (tiglyloxy [ benzoyloxy [ acetyloxy & isobutyryloxy) (Remy and Litaudon 2019). Esposito et al (2016) isolated six new jatrophane esters including euphodendroidins J-O (456-461) from the E. dendroides. The assessment of the antiviral activity of these compounds was performed in a virus-cell-based assay for the Chikungunya (CHIK) virus.…”

Feature-based Molecular Networking in the GNPS Analysis Environment

“…1b) with more than 600 jobs performed in August 2019 and has already been used in more than 80 publications using FBMN during its development since Nov 2017. The molecular networks generated with FBMN enable the efficient visualization and annotation of isomers in LC-MS 2 datasets, as demonstrated below with LC-MS 2 data from a drug discovery project from Euphorbia plant extract 9 (Fig. 2a-b), and the detection of human microbiome-derived lipids, belonging to the commendamide family 10 , detected in fecal samples from the American Gut Project 11 (a crowd-sourced citizen science microbiome project) (Fig.…”

Profiling of Hura crepitans L. latex by ultra‐high‐performance liquid chromatography/atmospheric pressure chemical ionisation linear ion trap Orbitrap mass spectrometry

“…A main characteristic of the plants belonging to the Euphorbiaceae family is the production of an irritant latex displaying many bioactive secondary metabolites with original structures wherein terpenoids, phloracetophenones, sphingolipids, flavonoids and steroids . Previous studies demonstrated that these compounds present many properties such as cytotoxicity, neurotrophic, molluscicidal, piscicidal, antiviral (HIV and chikungunya virus), tumour‐promoting activities and peripheral analgesic, anti‐inflammatory, anti‐arthritic effects . Moreover, some highly bioactive molecules occur only in the Thymelaceae and Euphorbiaceae families.…”

“…Euphorbia genus is a large source of diterpenes with 650 compounds yet isolated comprising 20 different skeletal types . The lower diterpenes in general have demonstrated many specific pharmacological activities especially modulating multidrug resistance cancer cells through modifications of protein kinases C (PKCs) expression, inhibition of P‐glycoprotein or activation of Transient Receptor Potential Vanilloid 1 . Sphingolipids are a class of ubiquitous compounds that can be found in vertebrate and invertebrate animals, higher plants, fungi and bacteria.…”