Guaiane Sesquiterpene Research Articles

Four new guaiane sesquiterpenes from Agarwood of Aquilaria sinensis and their biological activity toward renal fibrosis

Four undescribed guaiane sesquiterpenes, aquisinenoids I–L (2–5) and five known compounds were isolated from the resins of Aquilaria sinensis. Their structures were deduced based on spectroscopic data analysis, X-ray crystallography and ECD calculations. Biologically, compounds 1, 5, 6 and 9 showed anti-renal fibrosis activity, significantly reducing the levels of fibronectin, collagen I, and α-SMA. Compounds 2–4, 7 and 8 could reduce one or two of these proteins at non-toxic concentrations in TGF-β1 induced NRK-52E cells.

Highly oxidized guaiane 12(8),15(6)-dilactones with neuroprotective activities from the roots of Lindera aggregata (Sims) Kosterm

In our search for neuroprotective agents, six previously undescribed highly oxidized guaiane sesquiterpenes, linderaggrols A−F (1−6), together with three known sesquiterpenes, were isolated from the roots of Lindera aggregata (Sims) Kosterm. Their structures including absolute configurations were established by a combination of NMR spectroscopic techniques and single crystal X-ray diffraction experiments. Compounds 1−6 represented the first instances of guaiane 12(8),15(6)-dilactones. Additionally, compound 6 possessed a rare 1,8-O-bridge. Neuroprotective effects against erastin-induced ferroptosis on HT-22 cells showed that some compounds demonstrated neuroprotective effects at 20.0 μM.

Undescribed sesquiterpene-diterpene heterodimers from the fruits of Aphanamixis polystachya selectively modulate inflammatory markers in RAW 264.7 cells

Aphanapolystachones A–C (1–3), three undescribed sesquiterpene-diterpene heterodimers, were obtained from the fruits of Aphanamixis polystachya. Their structures and absolute configurations were identified by extensive analysis of HR-ESI-MS, NMR, experimental and TD-DFT calculated ECD spectra. The biosynthetic pathway of them was also proposed, which is produced by key intermolecular Diels-Alder [4 + 2]-cycloaddition reaction between a guaiane sesquiterpene and an acyclic diterpene. Compounds 1–3 inhibited NO production in LPS activated RAW 264.7 cells with the IC50 values of 1.7 ± 0.2, 3.0 ± 0.3, 5.3 ± 0.3 μM, respectively, lower than that of the positive control L-NMMA (31.5 ± 2.6 μM). In addition, compounds 1–3 significantly reduced IL-6 secretion at diluted concentration of 0.4 μM.

Ten undescribed eremophilane and guaiane sesquiterpenes from Penicillium roqueforti

Nine undescribed eremophilane sesquiterpenes, one undescribed guaiane sesquiterpene, along with ten known analogues were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures were elucidated on the basis of various spectroscopic analyses, mainly including NMR and HRESIMS data, 13C NMR calculations with DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, all twenty compounds were evaluated for the in vitro cytotoxic activities against seven human tumor cell lines, and the result suggested that 14-hydroxymethylene-1(10)-ene-epi-guaidiol A exhibited considerable cytotoxic activity against the Farage (IC50 < 10 μM, 48 h), SU-DHL-2, and HL-60 cells. Further mechanism study demonstrated that 14-hydroxymethylene-1(10)-ene-epi-guaidiol A could significantly promote apoptosis by inhibiting tumor cell respiration and decreasing intracellular ROS levels, thereby inducing S-phase blockade in tumor cells.

Cinnamigones A–C, three highly oxidized guaiane-type sesquiterpenes with neuroprotective activity from Cinnamomum migao

Cinnamigones A–C, three undescribed highly oxidized guaiane-type sesquiterpenes were isolated from the fruits of Cinnamomum migao. Cinnamigone A (1), structurally artemisinin-like, is a natural 1,2,4-trioxane caged endoperoxide with an unprecedented tetracyclic 6/6/7/5 ring system. Compounds 2–3 are classic guaiane sesquiterpene featuring different epoxy units. Guaiol (4) is considered to be the precursor of 1–3 in the biosynthesis pathway hypothesis. The planar structures and configurations of cinnamigones A–C were elucidated by spectral analysis, HRESIMS, X-ray crystallography and ECD calculations. Evaluation of the neuroprotective activity of 1–3 on N-methyl-ᴅaspartate (NMDA) toxicity was demonstrated that compounds 1–2 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity.

An Enantiospecific Synthesis of 5-epi-α-Bulnesene.

As a result of its unique fragrance and wider role in traditional medicine, agarwood produced in Aquilaria spp. and certain other trees has been harvested to near extinction as a natural phenomenon. Artificially induced agarwood production in Aquilaria plantations has sated some of the demand although the product quality is variable. Synthetic chemistry may have a role to play in providing sustainable routes to many of the fragrant components identified in agarwood and its smoke when burnt as incense. In this work, we report efforts towards a total synthesis of the guaiane sesquiterpene α-bulnesene, which is found, along with its more fragrant oxidised derivatives, in agarwood. Following the ring-expansion of (R)-carvone using reported procedures, α-butenylation gave a substrate for samarium diiodide mediated reductive cyclisation, the two butenyl epimers of the substrate each leading to a single bicyclic alcohol (24 and 25). Overall homoconjugate hydride reduction of one of these alcohols was achieved by Lewis acid-mediated ionisation and then hydride transfer from triethylsilane to complete an overall seven-step synthesis of 5-epi-α-bulnesene. This new synthesis paves the way for short routes to both α-bulnesene enantiomers and a study of their aerial and enzymatic oxidation products.

Germacrene B - a central intermediate in sesquiterpene biosynthesis.

Germacranes are important intermediates in the biosynthesis of eudesmane and guaiane sesquiterpenes. After their initial formation from farnesyl diphosphate, these neutral intermediates can become reprotonated for a second cyclisation to reach the bicyclic eudesmane and guaiane skeletons. This review summarises the accumulated knowledge on eudesmane and guaiane sesquiterpene hydrocarbons and alcohols that potentially arise from the achiral sesquiterpene hydrocarbon germacrene B. Not only compounds isolated from natural sources, but also synthetic compounds are dicussed, with the aim to give a rationale for the structural assignment for each compound. A total number of 64 compounds is presented, with 131 cited references.

Anti-Cancer Effect of Sesquiterpene and Triterpenoids from Agarwood of Aquilaria sinensis.

Two new guaiane sesquiterpenes, aquisinenoids A and B (1 and 2), two new eudesmane-type sesquiterpenoids, aquisinenoids C and D (3 and 4), one new cucurbitacin, aquisinenoid E (5), and five known cucurbitacins (6–10) were isolated from agarwood of Aquilaria sinensis. The structures of these new compounds, including their absolute configurations, were characterized by spectroscopic and computational methods. The biological evaluation showed that compounds 3 and 9 had an anti-cancer effect on most of the cancer cells at 5 μM, especially in human breast cancer cells. Interestingly, the new compound 3 exhibited more sensitivity on cancer cells than normal cells, highlighting its potential as a novel anti-cancer agent. Mechanically, compound 3 treatment increased the ROS generation and triggered apoptosis of human breast cancer cells.

Polyhydroxylated sesquiterpenes and ergostane glycosides produced by the endophytic fungus Xylaria sp. from Azadirachta indica

The investigation of the metabolites from the endophytic fungus Xylaria sp. YM 311647 in solid fermentation resulted in the isolation of six undescribed compounds, namely xylarioxides A–F, respectively. These included one eremophilane sesquiterpene, three guaiane sesquiterpene glycosides, and two ergostane glycosides. The structures of the compounds were determined by extensive analyses of spectroscopic data, including 1D and 2D NMR, as well as HRESIMS data. The stereochemistry of xylarioxide A was confirmed by X-ray crystallographic analysis. All of the isolated compounds were assayed for their antifungal activities against seven phytopathogenic fungi and two human pathogenic fungi. Among them, xylarioxides A, E and F showed potent activities against the tested phytopathogens. Particularly, xylarioxide E exhibited the highest activity against Gibberella saubinetii, Curvularia lunata, and Colletotrichum gloeosporioides with MIC values of 4, 4, and 8 μg/mL, respectively, which were comparable to the positive control of nystatin. Interestingly, guaiane sesquiterpene glycosides have been rarely reported from fungal sources. Additionally, xylarioxide E represented an unusual naturally occurring 3,4-seco-steroidal glycoside with a seven-membered lactone in ring A.

Guaiane sesquiterpenes from the gorgonian Echinogorgia flora collected in the South China Sea.

Echinoflorine (1), a new dimethylamino-substituted guaipyridine alkaloid with a novel γ-lactone-cyclohepta[c]pyridine fused skeleton, and three new guaiane sesquiterpene lactones, echinofloranolides A–C (2–4), together with eight known guaiane sesquiterpenes were isolated from the gorgonian Echinogorgia flora collected in the South China Sea. Their structures were elucidated by 1D and 2D NMR, HRESIMS, calculated ECD and DP4+ probability analyses.

Characteristic guaiane sesquiterpenes from Daphne penicillata and ECD/NMR-based assignment of C-1 configuration

40 compounds including the first C17 homo-guaiane sesquiterpene (1) were isolated from Daphne penicillata and an efficient method using ECD/NMR strategy to access the C-1 configuration of characteristic guaiane sesquiterpenes has been developed.

Three Unusual Sesquiterpenes with Distinctive Ring Skeletons from Daphne penicillata Uncovered by Molecular Networking Strategies

Daphnenoids A-C (1-3), three unusual sesquiterpenes with distinctive ring skeletons, together with a biogenetically related daphnenoid D (4) were obtained from the herb of Daphne penicillata by molecular networking strategies. Daphnenoid A (1) possesses a unique caged tetracyclo [5.3.2.01,6.04,11] dodecane scaffold by unexpected cyclizations of C-1/C-11 and C-2/C-14. Daphnenoids B and C (2 and 3) were the first discovered natural sesquiterpenes with unique 5/5 spirocyclic systems in nature. Their structures were determined by NMR spectroscopic analysis, computer-assisted structure elucidation methods, quantum chemical calculations, and X-ray diffraction. A hypothetical biogenetic pathway begins with typical guaiane sesquiterpene (a), including a key intermediate (4) was proposed. Daphnenoids B and C (2 and 3) exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.

Phytochemical Analysis of Anvillea garcinii Leaves: Identification of Garcinamines F-H and Their Antiproliferative Activities.

Anvillea garcinii is a medicinal plant used in the Arab region for intestinal diseases, lung and liver diseases, digestive problems, and as an antidiabetic agent. Repeated chromatographic purifications of A. garcinii leaves led to the isolation of three undescribed guaiane sesquiterpene derivatives, named garcinamines F–H, characterized by the presence of an amino acid unit, along with five known sesquiterpene lactones (garcinamines B–E and 9β-hydroxyparthenolide). The structures of the new compounds were established using spectroscopic (1D and 2D NMR) and spectrometric methods (ESIMS). Garcinamine H possesses a double bond at the Δ1,10 position, a structural feature rarely reported in guaianolide-type sesquiterpenes. The antiproliferative activity of the isolated sesquiterpenes was screened against three different cancer cell lines, and 9β-hydroxyparthenolide and garcinamines C and D displayed significant effects against lung carcinoma (A549), colon carcinoma (LoVo), and breast carcinoma (MCF7) cell lines.

Collective Syntheses of Guaiane Sesquiterpenes: Stereoselective Syntheses of (+)-Dysodensiol F, (+)-10β,14-Dihydroxy-allo-aromadendrane, and (-)-Dendroside C Aglycon.

A collective synthetic route for tricyclic guaiane sesquiterpenes and total syntheses of (+)-dysodensiol F, (+)-10β,14-dihydroxy-allo-aromadendrane, and (-)-dendroside C aglycon starting from a versatile hydroazulene intermediate were accomplished. The key features of these syntheses involve late-stage carbene-mediated diastereoselective cyclopropanation, construction of an unusual cis-fused-hydroazulene skeleton via intramolecular Dieckmann condensation, and highly stereoselective tandem conjugate addition/intramolecular allylic alkylation to afford a 5/7/3 tricyclic skeleton of guaiane natural products. The synthesis of (-)-dendroside C aglycon and the first total synthesis of (+)-dysodensiol F and (+)-10β,14-dihydroxy-allo-aromadendrane are described in detail. Activation of the Nrf2/ARE signaling pathway by (-)-dendroside C aglycon is also disclosed via our synthesis.

In vitro anti-Trypanosoma cruzi evaluation of sesquiterpenes from the branches of Oxandra sessiliflora

In this work, the CH2Cl2 phase from the EtOH extract of Oxandra sessiliflora (Annonaceae) branches was subjected to chromatographic fractionation to afford six sesquiterpenoids: 4α,10β-aromadendranediol (1), 4β,10α-aromadendranediol (2), 4α,10α-aromadendranediol (3), 1β,6α-dihydroxy-4(15)-eudesmene (4), 4β,10α-dihydroxy-guai-6-ene (5), and 4β,6β,7β,10α-tetrahydroxy-guaiane (6), the last one identified as a new natural product. The structures of isolated compounds were identified by analysis of NMR and HRESIMS spectral data. Compounds 1–6 exhibited activity against T. cruzi with EC50 values ranging from 16.3–47.5 μM. Additionally, no cytotoxicity to mammalian cells (NCTC- L929 clone) was observed for tested compounds at the highest concentration (200 μM). Sesquiterpenes 5 and 6 exhibited higher selectivity index (SI) with values higher than 12.3 and 11.4, respectively. This data suggests that guaiane sesquiterpenes 5 and 6, isolated from O. sessiliflora, may contribute as scaffolds for the design of novel and selective drug candidates for treatment of neglected diseases, mainly for Chagas disease.

Terpenoids from the Chinese liverwort Heteroscyphus coalitus and their anti-virulence activity against Candida albicans

In this study, 14 previously undescribed terpenoids were isolated from the Chinese liverwort Heteroscyphus coalitus (Hook.) Schiffner, including a rare harziane type diterpenoid, heteroscyphsic acid A; eight ent-clerodane diterpenoids, heteroscyphsic acids B–I; four labdane diterpenoids, heteroscyphins A–D; and one guaiane sesquiterpene, heteroscyphin E; as well as a known ent-junceic acid. Their structures were determined by a combination of MS, NMR spectroscopy, electronic circular dichroism (ECD) and single crystal X-ray diffraction analyses. The anti-virulence activity of the isolated compounds against Candida albicans DSY654 demonstrated that most of them could block hyphal growth at concentrations ranging from 4–32 μg/ml. Further investigation of the most active compound, heteroscyphin D, revealed that it could suppress the ability of C. albicans DSY654 to adhere to A549 cells and form biofilms, and modulate the transcription of related genes in this fungus.

Two new guaiane sesquiterpenes from the fruiting bodies of Lactarius Deliciosus

Two new guaiane sesquiterpenes, 7-(1-hydroxyethyl)-4-methyl-1-azulenecarboxaldehyde (1) and 7-isopropenyl-4-methyl-1-azulenecarboxylic acid (2), together with 5 known sesquiterpenes, were isolated from the fruiting bodies of Lactarius deliciosus. All structures were elucidated based on extensive spectroscopic methods, including 1 D and 2 D-NMR spectroscopy and high resolution mass spectrometry.

The Anti-Proliferative Activity of Anisosciadone: A New Guaiane Sesquiterpene from Anisosciadium lanatum.

The increase in cancer rate and the development of resistant tumors require a continuous search for new anticancer agents. This study aimed to analyze and identify the chemical constituents of Anisosciadium lanatum, and to investigate the antiproliferative activity of the identified constituents against various human cell lines (HepG2, MCF7, HT29, A549, and PC3) along with the possible molecular mechanisms involved. The structure of the isolated compounds was determined by spectroscopic techniques including HRFABMS, GC-MS, IR, and 400 MHz 1D and 2D NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY). The antiproliferative activity and IC50 value of the isolated compounds were measured and compared to doxorubicin. A new guaiane sesquiterpene containing a rare epoxide structural element, 10β,11β-epoxy-1α,4β,5β,7αΗ- guaiane-9-one, anisosciadone (1), and stigmasterol (2) have been isolated from the plant. Anisosciadone (1) showed a significant antiproliferative activity against liver, colon, and lung cells only, while stigmasterol (2) had a significant activity against liver, colon, and breast cells. Both 1 and 2 caused no cytotoxicity to normal fibroblasts. Anisosciadone elevated the expression and activity of Caspase 3 as well as p53 expression without affecting Caspase 9 in HepG2 cells. It also caused ~ 50% downregulation in cdk1 expression. Taken together, anisosciadone was specific in action against cancer cells and induced apoptosis in liver cells. It also has a unique feature by elevating the expression and activity of Caspase 3 without affecting the initiator Caspase 9. Therefore, anisosciadone deserves more investigation as a targeted therapy for cancer.

Isolation Process and Compound Identification of Agarwood Essential Oils from Aquilaria crassna Cultivated at Three Different Locations in Vietnam

Agarwood and agarwood essential oils are commodities with great commercial value. In Vietnam, the agarwood industry has been growing, with more than 10,000 ha of forest land reserved for the cultivation of Aquilaria crassna, an agarwood-producing tree. The aim of this study was to present a hydrodistillation process to recover agarwood essential oil and to compare chemical compositions of agarwood samples harvested from various locations in Vietnam. Three agarwood samples representing products from A. crassna trees cultivated in the provinces of Bac Giang and Khanh Hoa, and on the Phu Quoc island (Kien Giang province) of Vietnam were subjected to hydrodistillation, resulting in essential oil yields of 0.32%, 0.27%, and 0.25% (w/w), respectively. Using GC–MS analysis, a total of 44 volatile compounds were identified in the obtained oils. Most of the constituents were oxygenated sesquiterpenes and had been previously found in other agarwood oil samples. Notable compounds of other chemical classes were aromatics and fatty acids. The three oil samples showed a common volatile profile, which is characterized by the dominance of eremophilane, agarofurans, and eudesmane sesquiterpenes, while vetispirane and guaiane sesquiterpenes were found in smaller quantities. Desired compounds, such as neopetasane (7.47–8.29%), dihydrokaranone (2.63–3.59%), β-agarofuran (3.04–6.18%), and agarospirol (2.98–3.42%), were present in substantial quantities, suggesting that the essential oils could be commercialized as fragrant materials of high value.

Chemical profiling from water extract of Wikstroemia indica by UPLC-Q-TOF-MS/MS

In this study,a method using ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) was established to identify complicated chemical constituents of Wikstroemia indica. Chromatographic separation was performed on an AcclaimTMRSLC 120-C18 column( 2. 1 mm×100 mm,2. 2 μm) using gradient elution with 0. 2% ammonium formate buffer salt solution( A)-0. 2% ammonium formate buffer salt solution methanol( B) as mobile phase. The column temperature was maintained at 30 ℃. The analytes were determined by positive and negative ion modes with electro-spray ionization source. A total of 52 compounds( including eleven coumarins,thirteen flavonoids,ten lignans,two amides,four phenolic acids,six sesquiterpenes and six other compounds) were identified or tentatively characterized from the water extract of W. indica by comparing their retention times and MS spectra with those of authentic standards or literature datas. Three compounds were found for the first time from W.indica namely isomer of indicanone,β-hydroxypropiovanillone and epiprocurcumenol. Furthermore,the fragmentation rules of some compounds were speculated and summarized. In addition,the cleavage pathways of guaiane sesquiterpenes were described for the first time,which can provide reference for studying the fragmentation pathways of similar compounds. This study provides an easy way to identify chemical constituents of traditional Chinese medicine and a basis for the further study on chemical fundamentals of W. indica.