Inhibitory activities on mammalian central nervous system receptors and computational studies of three sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia

The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native γ-aminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the lactone at carbons 3 and 5, the presence of the hydroxyl group at position 6, and the different electronic distributions observed in tutin and coriamyrtin. The latter has an isopropenyl moiety at carbon 4 in contrast to the dihydrotutin isopropyl group at the same position, which could explain the difference in activity between dihydrotutin and tutin or coriamyrtin. The presence of the hydroxyl group at carbon 2 is not decisive since this functionality is present in tutin, the most active compound, and in dihydrotutin, the less active one.     

New compounds from the roots of Coriaria nepalensis

One new sesquiterpene lactone possessing novel variations in the structure, corialactone E (1), one new neolignan, coriarianeolignan A (2), together with three known apocarotenoids (3-5) and one known neolignan (6), have been isolated from a CHCl₃ extract of the roots of Coriaria nepalensis.     

Coriatone and corianlactone, two novel sesquiterpenes from Coriaria nepalensis

Both coriatone (1). a novel highly oxygenated picrotoxane-type sesquiterpene, and corianlactone (2). with an unprecedented sesquiterpene basic skeleton, named coriane, were isolated from Coriaria nepalensis Wall. The structures of 1 and 2 were determined by analysis of their two-dimensional NMR data, and the structure of 2 was confirmed by X-ray analysis. Compounds 1 and 2 showed no remarkable inhibitory activity toward K(562) cells. They are cytotoxic with IC(50) > 50 microg/mL (cis-platinim: IC(50) = 0.49 microg/mL).     

Biotransformation of aristolane- and 2,3-secoaromadendrane-type sesquiterpenoids having a 1,1-dimethylcyclopropane ring by Chlorella fusca var. vacuolata, mucor species, and Aspergillus niger

Biotransformation of the aristolane-type sesquiterpene hydrocarbon (+)-1(10)-aristolene (1) from the crude drug Nardostachys chinensis and of the 2,3-secoaromadendrane-type sesquiterpene lactone plagiochilide (2) from the liverwort Plagiochila fruticosa by three microorganisms, Chlorella fusca var. vacuolata, Mucor species, and Aspergillus niger was investigated. C. fusca var. vacuolata and Mucor sp. introduced oxygen function into the cyclohexane ring of aristolene while A. niger oxidized stereoselectively one methyl of the 1,1-dimethyl group on the cyclopropane ring of aristolanes and 2,3-secoaromadendrane to give C-12 primary alcohol and C-12 carboxylic acid. The possible metabolic pathway of the formation of new metabolites is discussed. The stereostructures of new metabolites were established by a combination of NMR spectroscopy including HMBC and NOESY, X-ray crystallographic analysis, and chemical reaction.     

A new sesquiterpene and other constituents from Saussurea lappa root

Five sesquiterpenes, dehydrocostus lactone (1), santamarine (5), beta-cyclocostunolide (6), 4alpha-hydroxy-4beta-methyldihydrocostol (7) and 10alpha-hydroxyl-artemisinic acid (9), along with four other compounds, beta-sitosterol (2), daucosterol (3), 5-hydroxymethyl-furaldehyde (4), and trans-syingin (8), were isolated and identified from the roots of Saussurea lappa (Compositae). Based on previous reports and our study, sesquiterpene derivatives are common and characteristic constituents of the genus Saussurea. Among the nine compounds obtained, 9 is a new sesquiterpene. It is an artemisinic acid derivative, whose structural skeleton has not been reported for Saussurea species before, but artemisinic acid is a common compound in another Compositae species, Artemisia annua. Dehydrocostus lactone (1) is present in high-content and is a possible bioprecursor of 10alpha-hydroxyartemisinic acid (9).     

13-Chloro-3-O-β-d-glucopyranosylsolstitialin from Leontodon palisae: the first genuine chlorinated sesquiterpene lactone glucoside

Apart from a number of known sesquiterpenoids, a novel chlorinated sesquiterpene lactone glucoside--13-chloro-3-O-β-d-glucopyranosylsolstitialin--has been isolated from the Southwestern European plant Leontodon palisae (Asteraceae, tribe Lactuceae). The structure has been established by high resolution mass spectrometry and 1D as well as 2D NMR spectroscopy. The compound represents the first naturally occurring chlorinated sesquiterpene lactone glucoside. The cytotoxicity of the new compound and related ones was evaluated using the MTT assay.     

Helivypolide G. A novel dimeric bioactive sesquiterpene lactone

In the course of our ongoing research for new allelochemicals from Helianthus annuus, a novel dimeric bioactive sesquiterpene lactone, helivypolide G has been isolated and characterized from the medium polar active fractions of the leaves of cultivar variety Stella. The monomers are connected through carbons C-15 of each unit and an oxygen bridge, forming an enolic oxane ring.     

Ainsliadimer A, a new sesquiterpene lactone dimer with an unusual carbon skeleton from Ainsliaea macrocephala

A phytochemical investigation of Ainsliaea macrocephala led to the isolation of a new dimeric sesquiterpene lactone, ainsliadimer A (1). The structure of 1 was elucidated by spectroscopic analysis, and confirmed by single crystal X-ray diffraction. Ainsliadimer A represents an unusual carbon skeleton with a cyclopentane system connecting the two monomeric sesquiterpene lactone units. This unique molecule exerted potent inhibitory activity against the production of nitric oxide in RAW264.7 stimulated by LPS.     

A New Sesquiterpene Lactone from Ainsliaea bonatii

A new sesquiterpene lactone, Ainsliaolide A, was isolated from Ainsliaea bonatii. The structure was determined on the basis of spectral data.     

A New Phytotoxic Sesquiterpene from Inula japonica

Chemistry of Natural Compounds - A new eudesmane sesquiterpene, 12-acetoxy-1β,2α-dihydroxyeudesma-4(15),11(13)-diene (1), was isolated from Inula japonica. The chemical structure of...     

Complete assignments of 1H and 13C NMR spectral data for three sesquiterpenoids from Inula helenium

The complete assignments of all the (1)H and (13)C NMR signals of three sesquiterpene lactones, 4-oxo-5(6),11-eudesmadiene-8,12-olide (1), 4-oxo-11-eudesmaene-8,12-olide (2) and (1(10)E)-5beta-Hydroxygermacra-1(10),4(15),11-trien-8, 12-olide (3), were carried out by various 2D NMR experiments. Compounds 1-3 were isolated from the roots of Inula helenium for the first time. Among them, 1 was identified as a new nor-sesquiterpene lactone, and 2 was isolated from a natural source for the first time. The (13)C-NMR data of compound 3 was also reported for the first time.     

Structure of anislactone A; a new skeletal type of sesquiterpene from the pericarps of Illicium anisatum

A novel sesquiterpene lactone was isolated from the pericarps of Illicium anisatum, a well known toxic plant in Japan, and its structure was established from spectral data and X-ray crystallographic analysis.     

Abietane diterpenoids from the barks of Cryptomeria japonica

From the bark of Cryptomeria japonica were isolated sugikurojins I (1) and J (2), and an abietane derivative (3) was obtained for the first time as a natural product. These structures were elucidated primarily through extensive NMR experiments. Sugikurojin I (1) has a unique skeleton incorporating an abietane diterpene and a 1,10-secocadinane sesquiterpene. Sugikurojin J (2) is a peroxyester of hydroxyabietane diterpene and isopimarane acid diterpene. Compound 3 was p-quinone acid, which occurred by cleavage between C-7 and C-8 of sugiol; it was deduced to [4'-isopropyl-1(S),3,3-trimethyl-3',6'-dioxo-bicyclohexyl-1',4'-dien-2(R)-yl]-acetic acid. Also obtained in this investigation were three known diterpenes (4-6).     

Structure elucidation and complete NMR spectral assignments of two new sesquiterpene lactone xylosides from Lactuca triangulata

Two new sesquiterpene lactone xylosides, derivatives of the guaianolides 9alpha-hydroxyleucodin and 9alpha-hydroxy-11,13-dehydroleucodin, were isolated from roots of Lactuca triangulata. Their structures were established on the basis of (1)H and (13)C NMR spectra, 2D NMR (HMQC, HMBC, COSY, NOESY) techniques and comparison with the literature data. The compounds represent the first example of sesquiterpene lactone xylosides.     

Terpenoids—XXI The structure of costunolide, a new sesquiterpene lactone from costus root oil

Costunolide, the new sesquiterpene lactone isolated from costus root oil (Saussurea lappa Clarke) is shown to have the structure I on the basis of dehydrogenation, ozonolyses and the formation of santanolide 'C' under mild conditions.     

Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides

Complete (1)H and (13)C NMR signal assignments of two lactucin-type sesquiterpene lactone glycosides, derivatives of 11β,13-dihydrolactucin, isolated from roots of Picris conyzoides, were achieved by one- and two-dimensional NMR experiments, allowing the correction of previously published data for cichorioside B and the structure elucidation of its new ester with 3-hydroxy-2-methylpropanoic acid. In addition, seven known sesquiterpene lactones and three phenolic compounds were isolated from the plant material.     

A New Sesquiterpene Lactones Glucoside from Notoseris psilolepis

As a part of an investigation on plant of the genus Notoseris (Asteraceae), an endemic genus of seed plants of China1, we studied the chemical constituents of N. psololepis Shih. A new sesquiterpene lactone glucoside, named notoserolide C (1) was isolated from the methanolic extract of the whole plant of N. psilolepis by repeated column chromatography (MCI GEL, normal and reversed phase silica gel). This compound showed antibacterial activity against Bacillu cereus.Figure 1. The key HMB…     

Sesquiterpene Lactones from Daucus glaber

Six new sesquiterpene lactone esters, daucoguaianolactones A–F ( 1 – 6 ), and one new sesquiterpene lactone, daucoeudesmanolactone A ( 7 ) were isolated from the leaves and stems of Daucus glaber (Forssk .) Thell ., along with the known sesquiterpene lactones talasins A and B and badkhysin. The structures of 1 – 6 were established on the basis of extensive 1D‐ and 2D‐NMR spectroscopic studies and that of 7 by X‐ray crystallography. Compounds 4, 7 , and talasins A and B showed moderate cytotoxicity against P‐388 leukemia cells.     

5β(H)-Austricin, a New Guaianolide from Artemisia leucodes

A new sesquiterpene lactone 5(H)-austricin was isolated from white wormwood (Artemisia leucodes Schrenk.). Its structure was established by chemical and spectral methods.     

Comparative analysis of sesquiterpene lactones from <Emphasis Type="Italic">Mikania cordifolia</Emphasis> collected from three different locations

The sesquiterpene lactone composition of extracts of Mikania cordifolia collected from Ribeirao Preto-SP (Brazil), Sao Carlos-SP (Brazil), and Campos de Jordao-SP (Brazil) were comparatively analyzed by HPLC. The results indicate that all specimens have the melampolide type sesquiterpene lactones analyzed and this kind of structure can be used as taxonomic marker for M. cordifolia. Published in Khimiya Prirodnykh Soedinenii, No. 2, pp. 117–118, March–April, 2007.