Sesquiterpene Skeleton Research Articles

Sesquiterpene constituents of the liverwort Lophozia ventricosa

The essential oil of Lophozia ventricosa was investigated and yielded the two new sesquiterpenoids ventricos-7(13)-ene and 6,7-epoxyeudesm-3-ene. The first has a new skeleton, which is named ventricosane and is numbered after the structurally closest known sesquiterpene skeleton pentalenane. The absolute configuration of the latter compound was established by conversion to known compounds. The isolated compounds and reaction products were investigated using enantioselective GC and extensive NMR measurements ( 1H; 1H– 1H COSY; HSQC; HMBC and NOE experiments).

New sesquiterpene dilactones from Mikania micrantha.

Four new sesquiterpene dilactones, mikamicranolide (1), 11 beta,13-dihydromikamicranolide (2), 3 alpha-hydroxy-11 beta,13-dihydrodeoxymikanolide (3), and 2 beta,3 beta-dihydroxy-11 beta,13-dihydrodeoxymikanolide (4), were isolated from the whole plants of Mikania micrantha. Their structures were elucidated on the basis of spectroscopic analysis. Compounds 1 and 2 possess an unusual rearranged 12,8-germacranolide sesquiterpene skeleton.

Trilobolide-6-O-isobutyrate, a eudesmanolide fromWedelia trilobata

The structure of trilobolide-6-O-isobutyrate, C23H32O9, isolated from the flower of Wedelia trilobata, shows an eudesmanolide sesquiterpene skeleton constructed from the fusion of two cyclo­hexane rings and a lactone ring.

Novel Sesquiterpenes and a Lactone from the Jamaican Sponge Myrmekioderma styx.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Macrocarpane, a new sesquiterpene skeleton from the leaves of Porcelia macrocarpa

The volatile oil and the hexane extract from the leaves of Porcelia macrocarpa (Warm.) R.E. Fries, Annonaceae, were submitted to chromatographic separations. Nine sesquiterpenes (a-cubebene, a-copaene, germacrene-D, bicyclogermacrene, g-cadinene, d-cadinene, spathulenol, globulol and cis-cubenol) and one diterpene (phytol) were identified in the volatile oil (83.1 % in weight). Two sesquiterpenes (spathulenol and macrocarp-11(15)-en-8-ol), the latter with a novel skeleton, one diterpene (phytol) and two steroids (sistosta-5,25-dien-3b-ol and sitosta-5,22,25-trien-3b-ol) were isolated from the hexane extract. These compounds were characterized by 1H and 13C NMR spectroscopy, including bidimensional analysis and mass spectrometry.

Probing sesquiterpene hydroxylase activities in a coupled assay with terpene synthases.

5-epi-Aristolochene dihydroxylase (EAH) catalyzes unique stereo- and regiospecific hydroxylations of a bicyclic sesquiterpene hydrocarbon to generate capsidiol. To define functional and mechanistic features of the EAH enzyme, the utility of a coupled assay using readily available sesquiterpene synthases and microsomes from yeast overexpressing the EAH enzyme was determined. Capsidiol and deoxycapsidiol biosyntheses were readily measured in coupled assays consisting of 5-epi-aristolochene synthase and EAH as determined by the incorporation of radiolabeled farnesyl diphosphate into thin-layer chromatography-isolated products and verified by gas chromatography-mass spectrometry analysis. The assays were dependent on the amounts of synthase and hydroxylase protein added, the incubation times, and the presence of nicotinamide adenine dinucleotide phosphate. The utility of this coupled assay was extended by examining the relative efficiency of the EAH enzyme to catalyze hydroxylations of different sesquiterpene skeletons generated by other terpene synthases.

Novel sesquiterpenes and a lactone from the Jamaican sponge Myrmekioderma styx

Two novel sesquiterpenes, styxone A ( 1 ) and styxone B ( 2 ), and a novel lactone, styxlactone ( 3 ), were isolated from the Jamaican sponge Myrmekioderma styx. Their structures were elucidated by detailed 1H, 13C and 2D NMR data and the absolute stereochemistry of styxone A and B was determined by CD spectra. Styxone A represents a novel sesquiterpene skeleton. ( S)-(+)-Curcuphenol ( 4 ), ( S)-(+)-curcudiol ( 5 ), and abolene ( 6 ) were also isolated. An activity enhancement by cyanthiwigin B ( 7 ) to curcuphenol was observed in the antimicrobial assays when the two compounds were administered together.

Insecticidal sesquiterpene pyridine alkaloids from Euonymus species

Three insecticidal sesquiterpene pyridine alkaloids with a β-dihydroagarofuran sesquiterpene skeleton, euoverrine A ( 1 ), B ( 2 ), and euophelline ( 3 ), and a known compound, euojaponine C ( 4 ), were isolated from the root bark of Euonymus verrucosides, E. fortunei and E. phellomana by bioassay-guided fractionation. Their chemical structures were elucidated mainly by analyses NMR and MS spectral data.

Quirogane, prenopsane, and patzcuarane skeletons obtained by photochemically induced molecular rearrangements of longipinene derivatives.

Ultraviolet irradiation of (1R,3S,4S,5S,10R,11R)-1-acetyloxy-7-oxolongipin-8-ene (6), prepared from longipinene diesters isolated from Stevia salicifolia, afforded the new quirogane (7) and prenopsane (8) derivatives, as the major products, together with the minor secondary photoproduct (1R,3R,5R,8S,11S)-1-acetyloxy-7-oxopatzcuar-9-ene (9), which possesses a novel tricyclic sesquiterpene skeleton. The stereostructures of the new compounds 7-9 were mainly determined by NMR techniques including COSY, HSQC, HMBC, and NOESY in combination with molecular modeling obtained by density functional theory calculations. A reaction mechanism accounting for the observed transformations is proposed.

A novel approach for construction of the naturally occurring dihydroagarofuran sesquiterpene skeleton

A general and efficient approach for the synthesis of a kind of dihydrofuran sesquiterpenes extensively present in the Celastraceae family of plants has been developed by a series of transformations from santonin. The key creative and versatile steps involve the strategic acid-catalyzed double-bond shifting affording 6 , the novel base-promoted epoxide rearrangement of 7 generating two key functions (the C5OH and the Δ 7,11 double bond) and the stereoselective construction of a tetrahydrofuran moiety without particularly controlling the stereochemistry of C7. In particular, this approach can introduce any number of hydroxyls at the required positions for synthesis of many natural dihydroagarofuran sesquiterpenes.

Bioactive sesquiterpenes produced by fungi: are they useful for humans as well?

Higher fungi are characterised by the production of macroscopic fruiting bodies to generate and to distribute their spores. These fruiting bodies are under constant threat of other organisms feeding on them. As a consequence these organisms developed a number of strategies for protection, one of them is the production of toxins. The fungal subdivision Basidiomycotina produce toxic sesquiterpenes many of them are derived from the protoilludane skeleton. This skeleton is transformed and rearranged to a large number of compounds. Some of these sesquiterpenes show interesting biological properties which may be attractive for medicinal chemistry. The overview describes the different types of bioactive fungal sesquiterpenes derived from humulene known to date in Basidiomycotina and their formation. The metabolites are discussed according to their sesquiterpene skeleton and the different metabolites are compared. Where available biological activities concerning antifungal, antibacterial, cytotoxic and enzyme inhibition data are given. Special attention was paid for the different activities of these metabolites and the attempts made to use them in medicinal chemistry. The question whether metabolites produced for the self-protection of fungi can be used for pharmaceutical applications for humans will be addressed and discussed.

Pacifigorgianes and tamariscene as constituents of Frullania tamarisci and Valeriana officinalis

The sesquiterpenoid constituents of the essential oils from the liverworts Frullania tamarisci, Frullania fragilifolia and of the angiosperm Valeriana officinalis were investigated. Tamariscene, a compound with a new sesquiterpene skeleton, valerena-4,7(11)-diene and five new pacifigorgiadienes, namely pacifigorgia-1,10-diene, pacifigorgia-1(6),10-diene, pacifigorgia-1(9),10-diene, pacifigorgia-2,10-diene, and pacifigorgia-2(10),11-diene were isolated and identified. Structure elucidation was carried out by NMR spectroscopy and chemical correlations to establish absolute configurations. Compounds present in both the essential oils of the Frullania species and Valeriana officinalis were enantiomeric to each other. A plausible biogenetic relationship between the pacifigorgiane, valerenane and tamariscane skeletons is postulated. Pacifigorgia-6,11-diene, not yet detected in nature, was generated by dehydration and rearrangement of natural (−)-tamariscol.

A NOVEL BASE-PROMOTED REARRANGEMENT OF EUDESMANOLIDE SESQUITERPENOID TO THE SALVIALANE SESQUITERPENE

An eudesmanolide sesquiterpene epoxide has been transformed to an α-hydroxy ketone with the salviane sesquiterpene skeleton through a novel carbon-carbon rearrangement promoted by excess of NaOMe in Et2O at room temperature which accomplished the first synthesis of the salviane kind of sesquiterpene skeleton. A possible reaction mechanism is also discussed.

Synthesis of Tricyclic Ketones with Sesquiterpene Skeletons by Acid-Catalyzed Rearrangement ofβ-Monocyclofarnesol

Starting from dihydro-β-ionone (6) a mixture of three tricyclic ketones with sesquiterpene skeletons 14, 15, and 16 was prepared by Wittig-Horner reaction with triethyl phosphonoacetate, Red-Al® reduction, acid-catalyzed rearrangement of the resulting β-monocyclofarnesol (7), alkaline hydrolysis of the formates 8 – 10, and subsequent molybdenium-catalyzed oxidation. The mechanistic background of the acid-catalyzed rearrangement of β-monocyclofarnesol (7) is discussed in detail. The resulting tricyclic ketones 14 – 16 exhibit intense woody odor notes with peppery vetiver or camphoraceous cedarwood aspects.

An approach to the tremulane skeleton: Synthesis of (±)-6a- epi-tremulenolide B and related hydroazulenes

An approach to the skeleton of the tremulane sesquiterpenes and the synthesis of the title compound 8 are described.

Patch testing for Compositae allergy.

The main allergenic constituents of Compositae plants are the sesquiterpene lactones (SLs). In recent years, a mixture of three SLs, each with a different sesquiterpene skeleton (alantolactone, dehydrocostuslactone or costunolide), has been routinely used to detect Compositae allergy. The purpose of our study was to establish the value of testing with a range of Compositae extracts. Ninety-seven consecutive patients with exposure pattern dermatitis or hand eczema and gardening as a hobby or occupation were patch tested to the European standard series including SL mix 0.1% pet., Compositae extracts and other relevant allergens. Twenty-six of the 97 patients tested showed allergic reactions to SL mix or Compositae extracts. Fifteen of these showed positive reactions to both the SL mix and Compositae extracts. Eleven patients showed a negative reaction to the SL mix but positive reaction to the Compositae extracts. Dandelion elicited a positive reaction in eight of the 11 SL mix-negative patients and three patients reacted to feverfew. The SL mix failed to detect 38% of our Compositae-sensitive patients. Dandelion extract alone detected 73% of SL-negative patients. Additional testing with feverfew extract would have detected 91% of the SL mix-negative individuals. Our study highlights the importance of testing the response of SL-negative patients to additional Compositae extracts when there is a clinical suspicion of Compositae allergy.

The structures of three novel sesquiterpenoids from Valeriana jatamansi Jones

Three new sesquiterpenoids valeriananoids A ( 1), B ( 2) and C ( 3), possessing an unprecedented sesquiterpene skeleton, have been isolated from the roots and rhizomes of Valeriana jatamansi Jones. The structures were elucidated by chemical and spectroscopic means and, in the case of 1, confirmed by X-ray crystallography.

The biosynthesis of the new tremulane sesquiterpenes isolated from Phellinustremulae

The tremulane sesquiterpenes isolated from the wood-rotting fungus Phellinustremulae are irregular isoprenoids derived from the cyclization and rearrangement of farnesyl pyrophosphate (FPP). The most interesting feature in the formation of the tremulane skeleton seems to involve the migration of a methyl group from one of the isoprene units. To investigate the biosynthetic origin of this unique sesquiterpene skeleton, labelling experiments were carried out by adding 13C-labelled sodium acetate to liquid cultures of Phellinustremulae. The labelling pattern was determined by 13C NMR spectral analysis of labelled tremulenediol A, which was purified as its di-p-bromobenzoate. A possible route to the tremulane skeleton, which accounts for the observed labelling pattern, proceeds from FPP, via humulene. The stereochemical course of the tremulane biosynthesis is discussed. Keywords: fungal metabolites, aspen, perhydroazulene sesquiterpenes, labelling experiments.

Synthesis based on cyclohexadienes. Part 24.1 A new total synthesis of pupukean-2-one and a facile entry to copa and ylanga type sesquiterpene skeletons

A novel tandem 5-exo-trig allyl and 3-exo-trig radical cyclisation and rearrangement to copa and ylanga type sesquiterpene skeletons from easily prepared cyclohexadienes is reported. A new total synthesis of pupukean-2-one 8, which belongs to a novel class of sesquiterpenes, involving a 5-exo-trig allyl radical cyclisation as the key step is also reported.

Photochemical rearrangements of highly functionalized longipinene derivatives

Ultraviolet irradiation of 7β,9α-diacetyloxylongipin-2-en-1-one ( 3) affords the vulgarone A derivative 5 and compound 7 which possesses a novel tricyclic sesquiterpene skeleton named pingilonane. The photorearrangements of 3 occur via [1,3] sigmatropic shifts of the C 4C 10 or of the C 4C 5 bond, respectively. Similarly, irradiation of 7β,8α,9α-triacetyloxylongipin-2-en-1-one ( 4) affords 6 and 8. Some biogenetic implications of these transformations are discussed.