Sesquiterpene lactones studies

Jorgensen et al. [84] studied how solvent effects could influence the course of Diels-Alder reactions catalyzed by copper(II)-bisoxazoline. They assumed that the use of polar solvents (generally nitroalkanes) improved the activity and selectivity of the cationic copper-Lewis acid used in the hetero Diels-Alder reaction of alkylglyoxylates with dienes (Scheme 31, reaction 1). The explanation, close to that given by Evans regarding the crucial role of the counterion, is a stabilization of the dissociated ion, leading to a more defined complex conformation. They also used this reaction for the synthesis of a precursor for highly valuable sesquiterpene lactones with an enantiomeric excess superior to 99%. 

One final comment on the biological activity of the sesquiterpene lactones in relation to ENE disease in horses. Unfortunately, horses are the only animal which contract this disease. Consequently, acquiring sufficient pure material to be fed to horses becomes a formidable task. At the present time, trial studies are being initiated with solstltlalln-A to observe its effect on horses. Insufficient material is available to permit the testing of the other sesquiterpene lactones. 

Effects of Sesquiterpene Lactones on Seed Germination. Sesquiterpene lactones are common constituents of the Asteraceae but are also found in other angiosperm families and in certain liverworts (31,32). These highly bitter substances exhibit a wide spectrum of biological activities (J 3) which include cytotoxicity, anti-tumor, anti-microbial, insecticidal (34) and molluscicidal (35) properties. Furthermore, they are known causes for livestock poisoning and contact dermatitis in humans (33). Structure-activity relationship studies on sesquiterpene lactones have demonstrated that biological activity frequently depend on the presence of the cr... 

In 1959-61, a Czech group [8,9] reported the isolation of a new sesquiterpene lactone from Chrysanthemum (Tanacetum) parthenium as part of a study of the sesquiterpene lactones of the Compositae family. They named it parthenolide. The initial structure for parthenolide was later revised [10,11] and the accepted structure for parthenolide today is represented by structure (1). Parthenolide is a germacranolide-type sesquiterpene lactone. The crystal structure for parthenolide has also been reported [12]. Extractions of C. (T.) parthenium grown in Mexico, known locally as santamaria, did not yield parthenolide [13], but a closely related compound was isolated and named santamarine (3). This suggests that regional variations in the chemical constituents may occur. 

Parthenolide was only the first of many sesquiterpene lactones to be isolated from feverfew. Two further compounds were isolated and named chrysartemin A (4) and B (5) [14]. The structure of chrysartemin B was later revised [15], Recently, several studies have shown that chrysartemin A and B are not present in feverfew as the structures shown in (4) and (5) but are in fact the isomeric canin (19) and artecanin (20), respectively (see... 

One of the first biological activities for which sesquiterpene lactones were screened was their possible anti-tumour activity. Studies have shown that... 

The ability of feverfew extract to inhibit 5HT-secretion in platelets was used to identify compounds responsible for the inhibitory effects on platelets [44], A crude feverfew extract was separated by chromatography and fractions were screened for antisecretory activity induced by adrenaline. In five active fractions compounds were identified as the sesquiterpene lactones parthenolide (1), canin (19), artecanin (20), secotanapartholide A (24) and 3 8-hydroxyparthenolide (2). The ability of parthenolide to affect platelet activity induced by other agents was confirmed in a study of direct comparison of crude feverfew extract with parthenolide [43], Parthenolide in the micromolar concentration range inhibited platelet 5HT-secretion. 

The capsules contained a mean of 82 mg feverfew and thus the level of activity calculated as parthenolide can be estimated as 0.67%. Other studies quote 0.87% sesquiterpene lactones calculated as parthenolide [27] and 0.25-0.30% of active (antimicrobial) material [33]. Bohlmann s extraction of individual components from the dried plant yielded 116 mg sesquiterpene lactones/kg dried feverfew which amounts to less than 0.01 % [17]. Another extraction yielded 330 mg endoperoxides/kg and 56 mg canin/kg alone [19] which would amount to a level of sesquiterpene lactones of at least 0.04%. Thus, the level of sesquiterpene lactones appears to vary with different sources of the plant and this could have been due to a number of factors including the conditions in which feverfew was grown, the season in which it was picked and the way in which it was stored. Another important determinant of the parthenolide content of feverfew appears to be the geographical location. A recent survey of commercial preparations found that all the North American commercial products tested contained less that 0.1% parthenolide, wheras much higher values were obtained for British products. A minimum level of 0.2% parthenolide in commercial products has been proposed by the Health Protection Branch of Health and Welfare Canada [71]. 

Artemisinin (8) doperoxide sesquiterpene lactone Arterolane (RBX11160, OZ-277) (64) Antiparasitic (antimalarial) Under study (on interation of peroxide moiety with parasite targets) Phase III Ranbaxy 561-565... 

Fig. 1.7. Sesquiterpene lactones and thiophenes isolated from species of the Aster-aceae used in synergism study.

Although the first survey listed 45 natural chlorinated sesquiterpene lactones, several such compounds were omitted in that coverage (1) and are described here. The novel sesquiterpene lactone chlorochrymorin (239) was isolated from Chrysanthemum morfolium (499), and the chlorohydrin graminichlorin (240) is found in Liatris graminifolia (500). The antibacterial AA-57 (241), which is related to pentalenolactone, is produced by a Streptomyces sp. (501). The plant Eupatorium chinense var. simplicifolium has yielded eupachifolin D (242) (502) (side-chain double bond stereochemistry revised (518)), and the new guaianolide andalucin (243) was characterized from Artemisia lanata (503). The previously known chlorohyssopifolins (1) have been studied for cytostatic activity, and the presence of one and even two chlorine atoms amplifies this activity (504). 

Hamburger M, Wolfender J-L, Hostettmann K (1993) Search for Chlorinated Sesquiterpene Lactones in the Neurotoxic Thistle Centaurea solstitialis by Liquid Chromatographic-Mass Spectrometry, and Model Studies on Their Possible Artifactual Formation. Nat Tox 1 315... 

Robles M, Aregullin M, West J and Rodriguez E (1995) Recent studies on the zoopharmacognosy, pharmacology and neurotoxicology of sesquiterpene lactones. Planta Med 61, 199-203. 

Fischer, N.H., Weidenhamer, J.D., Riopel, J.L., Quijano, L., Menelaou, M.A. Stimulation of witchweed germination by sesquiterpene lactones a structure-activity study. Phytochemistry 1990 29 2479-2483. 

Galindo, J.C.G., de Luque, A.P., Jorrin, J., Macias, F.A. SAR studies of sesquiterpene lactones as Orobanche cumana seed germination stimulants. J Agric Food Chem 2002 50 1911-1917. 

Sunflower is a rich source of sesquiterpenes,21 especially sesquiterpene lactones.23,28 31 44 Due to its economic importance, sunflower has been extensively studied, thus leading to the isolation and chemical characterization of phenolic compounds (benzoic acid derivatives,9 39,51 coumarins,51 and flavonoids6,10,19), diterpenes, and triterpenes. Most of these studies were performed using... 

Often used in concert with mass spectrometry, NMR spectroscopy remains an invaluable structural diagnostic tool of particular importance to tricyclic natural products chemistry. For example, the tricyclic phenolic compound moracin P (3) was one of eight previously known compounds identified together with two new isoprenoid-substituted flavanones in isolates of the root bark of mulberry trees <89H(29)807>. In a series of studies of 6-7-5 tricyclic natural products, ID and 2D H and l3C NMR spectroscopy were employed extensively in the structure determination of sesquiterpene lactones (4)—(8) found among the aerial natural products of toxic plants (85P1378,90P551, 90P3875). 

TOPQU, G., CORDELL, G.A., FARNSWORTH, N.R. FONG, N.H., Studies on zoapatle. VIII. Novel cytotoxic sesquiterpene lactones from Montanoa tomentosa ssp. microcephala., J. Pharm. Sci., 1988, 77,553-556. 

A case of anomalous 1,3-dioxolane formation has been reported when the sesquiterpene lactone parthenin 9 is treated under Baylis-Hillman conditions with aromatic aldehydes and affords products of type 10 <07TL955>. A computational study of copper-catalysed carbonyl... 

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