Constituents of Bupleurum praealtum and Bupleurum veronense with Potential Immunomodulatory Activity

Abstract

In this investigation, chromatographic separations of the diethyl ether extracts of two European annual Bupleurum taxa, B. praealtum and B. veronense, yielded nine new natural products, namely, a series of esters of stereoisomeric tetradeca-5,7,9,11tetraen-1-ols (1−4 and 8), a tetra-unsaturated γ-tetradecalactone (5), a dibenzylbutyrolactone lignan (7-oxoarcitin, 6), a falcarinolrelated 17-membered macrolide (7) possessing a conjugated diyne-system, and an acylphloroglucinol derivative (9). All these new compounds were fully characterized by NMR, IR, UV, MS, and optical rotation measurement, including 1 H NMR full spin spectral simulation, whereas the absolute configurations of 1, 5, and 9 were determined via chemical correlations and NMR analysis of Mosher esters. The in vitro potential immunomodulatory activities of 1, 4, 5, and (+)-arcitin were assessed by determining their effects on the functional properties of isolated rat splenocytes and peritoneal macrophages. The results obtained support the known immunomodulatory ethnomedicinal usage of Bupleurum species.

The enantioselective total syntheses of (+)-7-oxohinokinin, (+)-7-oxoarcitin, (+)-conicaol B and (−)-isopolygamain

“…7-Oxoarcitin (1) is a recently isolated lignan, found in 2020 in Bupleurum praealtum schizocarp extract. 9 The structure was deemed similar to the well-known (+)-arcitin, which was also isolated from the same plant, but through analysis of its NMR, MS and IR spectra was determined to be an oxygenated deriva-tive. Additionally, 1 H NMR showed the compound to exist solely in the keto tautomeric form.…”

“…1,3,4 Ketone functionalisation is present at either one or both of the benzylic carbons (C-7 or C-7′) in only a few natural lignans. [9][10][11] Whilst natural dibenzyl butyrolactone frameworks have been well studied in the literature, there have been limited syntheses of compounds with substitution at the C-7 position. [12][13][14] The therapeutic potential and unexplored complex structures make these compounds interesting synthetic targets.…”

“…7-Oxoarcitin (1), conicaol B (2),7-oxohinokinin (3) and (2R,3S)-2-(4-hydroxy-3,5-dimethoxybenzoyl)-3-(5-methoxy-3,4methylenedioxybenzyl)butyrolactone are the only reported natural dibenzyl butyrolactones containing ketone functionalisation at C-7, with the remainder of the structure following the classic framework of this lignan class. 9,11,15,16 These natural products contain two contiguous stereocentres in a trans relationship (8S,8′R) and are differentiated in structure only by their aromatic substitutions (Fig. 1).…”

“…A trans relationship between the C-8/C-8′ stereocenters was suggested but NOESY analysis gave inconclusive results, leaving the exact stereochemistry undetermined. 9 The similar lignan conicaol B (2) was isolated for the first time from Saussurea conica in 2006. 11 The two stereocenters were assigned in a trans relationship through their NOESY correlations and by comparison of their NMR data with similar known compounds that were simultaneously isolated.…”

Methyl and Isopropyl N‐Methylanthranilates Affect Primary Macrophage Function – An Insight into the Possible Immunomodulatory Mode of Action

“…To assess in vitro effects of MMA and IMA on macrophage ability to metabolize MTT, eMϕs were treated with these compounds, in the concentration range from 0.25 μM to 25 μM, for 1 h (short-term cell culture). This assay, although regularly used for screening cytotoxicity, [3,[32][33][34] reveals only the possible inhibiting or activating activity of the tested compounds on these mitochondrial enzymes. MMA and IMA caused a statistically significant concentration-dependent decrease of eMϕ ability to metabolize MTT (Figure 1).…”