Aromatic Sesquiterpenes Research Articles

Two New Aromatic Sesquiterpenes from the Leaves of Nicotiana tabacum and Their Aroma Character

Two New Aromatic Sesquiterpenes from the Leaves of Nicotiana tabacum and Their Aroma Character

Two New Antifungal Aromatic Sesquiterpenes from the Leaves of Cigar Tobacco

Two New Antifungal Aromatic Sesquiterpenes from the Leaves of Cigar Tobacco

Valencene, Nootkatone and Their Liposomal Nanoformulations as Potential Inhibitors of NorA, Tet(K), MsrA, and MepA Efflux Pumps in Staphylococcus aureus Strains.

Valencene and nootkatone are aromatic sesquiterpenes with known biological activities, such as antimicrobial, antioxidant, anti-inflammatory, and antitumor. Given the evidence that encapsulation into nanosystems, such as liposomes, could improve the properties of several compounds, the present study aimed to evaluate the activity of these sesquiterpenes in their isolated state or in liposomal formulations against strains of Staphylococcus aureus carrying efflux pumps. The broth microdilution method evaluated the antibiotic-enhancing activity associated with antibiotics and ethidium bromide (EtBr). The minimum inhibitory concentration was assessed in strains of S. aureus 1199B, IS-58, and RN4220, which carry the efflux proteins NorA, Tet(K), and MsrA. In tests with strain 1199B, valencene reduced the MIC of norfloxacin and EtBr by 50%, while the liposomal formulation of this compound did not show a significant effect. Regarding the strain IS-58, valencene, and its nanoformulation reduced norfloxacin MIC by 60.3% and 50%, respectively. In the non-liposomal form, the sesquiterpene reduced the MIC of EtBr by 90%. Against the RN4220 strain, valencene reduced the MIC of the antibiotic and EtBr by 99% and 93.7%, respectively. Nootkatone and its nanoformulation showed significant activity against the 1199B strain, reducing the EtBr MIC by 21.9%. Against the IS-58 strain, isolated nootkatone reduced the EtBr MIC by 20%. The results indicate that valencene and nootkatone potentiate the action of antibiotics and efflux inhibitors in strains carrying NorA, Tet(K), and MsrA proteins, which suggests that these sesquiterpenes act as efflux pump inhibitors in S. aureus. Therefore, further studies are needed to assess the impact of incorporation into liposomes on the activity of these compounds in vivo.

Influence of the Drying Method on the Volatile Component Profile of Hypericum perforatum Herb: A HS-SPME-GC/MS Study

Hypericum perforatum L. (St. John’s wort) is one of the most popular medicinal plants in the world. Due to its documented antimicrobial and antioxidant properties, it is used in the treatment of bacterial and viral infections as well as inflammations. It is also used to treat gastrointestinal diseases and mild to moderate depression. In recent years, there has been an increase in the popularity of herbal medicine. Many people collect their own herbs and dry them at home. A common choice for quick drying of fruits, vegetables and herbs at home are food dehydrator machines. There are not many publications in the scientific literature examining the quality of dried herbal material obtained in such dryers. We characterized St. John’s wort harvested in southern Poland and investigated the effect of specific drying methods on the volatile component profile. The herbal raw material was dried using three methods: indoors at room temperature, in an incubator at 37 °C and in a food dehydrator machine. Volatile components were analysed by HS-SPME GC/MS. The herb dried in a food dehydrator, compared to other drying methods, retained similar or slightly smaller amounts of the compounds from the mono- and sesquiterpenes group, aromatic monoterpenes, aromatic monoterpenoids, sesquiterpenoids, aromatic sesquiterpenes and alkanes. However, monoterpenoids and compounds coming from decomposition reactions, such as alcohols, short-chain fatty acids and esters, were noticed in larger quantities. Usage of a food dehydrator at home can be a convenient alternative to drying herbs. However, due to a different profile of volatile components depending on the drying method, the amount of biologically active substances needs to be considered. By using various methods of drying, the medical effects of herbs can be enhanced or weakened; therefore, further research in this direction should be continued.

Electrophysiological Responses of the Mediterranean Fruit Fly, Ceratitis capitata, to the Cera Trap® Lure: Exploring Released Antennally-Active Compounds

The Mediterranean fruit fly (medfly), Ceratitis capitata, is a worldwide pest of agriculture able to use olfactory cues to locate habitat, food sources, mates and oviposition sites. The sensitivity of medfly olfaction has been exploited to develop olfactory-based attractants that are currently important tools for detection, control and eradication of its populations. Among these is Cera Trap® (BIOIBERICA, S.A.U.), a cost-effective bait. Here we used coupled gas chromatography/electroantennographic detection (GC-EAD) and GC/mass spectrometry (GC-MS) approaches to characterize the medfly antennally-active compounds released by this lure. We identified GC peaks corresponding to chemicals belonging to six different classes including heterocyclic aromatic compounds, aliphatic alcohols, aldehydes, esters, sesquiterpene hydrocarbons, and aromatic alcohols. We tested ten potential candidate volatiles belonging to these classes and predicted to be emitted by the lure and found that they were eliciting electroantennographic responses in medfly adults. These results will help in unravelling the physiological mechanisms of odor perception in both sexes, especially in relation to Cera Trap® attractant activity, which in the field has been shown to be female-specific. These findings and their developments will ultimately expand the toolbox for medfly control in the field.

Catalytic enantioselective total synthesis of (−)-ar-Tenuifolene

First catalytic asymmetric total synthesis of aromatic sesquiterpene, (−)-ar-teunifolene (1) is featured (3 steps, 75% overall yields) from commercially available 3-methyl cyclohex-2-enone 16. The enantioenriched 3,3-disubstituted cyclohexanone 11 is obtained from Pd(II)-catalyzed enantioselective (p-tolyl)boronic acid addition to 3-methyl cyclohex-2-enone 16 in 90% ee, which is found to be the key intermediate. A diastereoselective methyllithium addition of this enantioenriched product followed by dehydration completes straightforward access to (−)-ar-teunifolene (1).

Concise total syntheses of (+)- and (−)-ar-macrocarpene

Concise catalytic asymmetric total syntheses of both the enantiomers of aromatic sesquiterpenes, (+)-ar-macrocarpene (1) and (–)-ar-macrocarpene (ent-1) is featured in 4 steps, 66.0% overall yields from commercially available 5,5-dimethylcyclohexane 1,3-dione 13. The enantioenriched 5,5-dimethyl-3-(p-tolyl)cyclohexanone 10 is found to be the key intermediate, which was obtained from catalytic enantioselective p-tolylboronic acid addition onto enone 11 using Pd(II)-(S,S)-DUPHOS (ent-L5) in >99% ee. Finally, a Wolf-Kishner reduction of cyclohexanone 10 completes straightforward access to naturally occurring sesquiterpenoid, (+)-ar-macrocarpene (1).

Catalytic asymmetric total syntheses of sesquiterpenoids, (+)- and (−)-ar-macrocarpene

Concise catalytic asymmetric total syntheses of aromatic sesquiterpenes, naturally occurring (+)-ar-macrocarpene (1) and unnatural (−)-ar-macrocarpene (ent-1) have been featured (6 steps, ∼60–61% overall yields) from commercially available 4,4-dimethylcyclohex-2-enone 16. The enantioenriched allyl alcohol 12 is obtained from catalytic enantioselective reduction of enone 13b using Corey-Bakshi-Shibata catalyst in 93% ee, which is found to be the key intermediate. A highly diastereoselective hydrogenation of enantioenriched allyl alcohol 12 (10.3:1 dr) followed by deoxygenation completes straightforward access to (+)-ar-macrocarpene (1) and (−)-ar-macrocarpene (ent-1).

Isolation and Potential Biological Applications of Haloaryl Secondary Metabolites from Macroalgae.

Macroalgae have been reported as an important source of halogenated aromatic secondary metabolites, being the majority of these derivatives isolated from red algae. Halophenols and haloindoles are the most common haloaryl secondary metabolites isolated from these marine organisms. Nevertheless, some halogenated aromatic sesquiterpenes and naphthalene derivatives have also been isolated. Most of these secondary metabolites showed interesting biological activities, such as antitumor, antimicrobial, antidiabetic, and antioxidant. This review describes in a systematic way the distribution and natural occurrence of halogenated aromatic secondary metabolites from extracts of red, brown, and green algae, as well as biological activities reported for these compounds.

Functional Characterisation of New Sesquiterpene Synthase from the Malaysian Herbal Plant, Polygonum Minus.

Polygonum minus (syn. Persicaria minor) is a herbal plant that is well known for producing sesquiterpenes, which contribute to its flavour and fragrance. This study describes the cloning and functional characterisation of PmSTPS1 and PmSTPS2, two sesquiterpene synthase genes that were identified from P. minus transcriptome data mining. The full-length sequences of the PmSTPS1 and PmSTPS2 genes were expressed in the E. coli pQE-2 expression vector. The sizes of PmSTPS1 and PmSTPS2 were 1098 bp and 1967 bp, respectively, with open reading frames (ORF) of 1047 and 1695 bp and encoding polypeptides of 348 and 564 amino acids, respectively. The proteins consist of three conserved motifs, namely, Asp-rich substrate binding (DDxxD), metal binding residues (NSE/DTE), and cytoplasmic ER retention (RxR), as well as the terpene synthase family N-terminal domain and C-terminal metal-binding domain. From the in vitro enzyme assays, using the farnesyl pyrophosphate (FPP) substrate, the PmSTPS1 enzyme produced multiple acyclic sesquiterpenes of β-farnesene, α-farnesene, and farnesol, while the PmSTPS2 enzyme produced an additional nerolidol as a final product. The results confirmed the roles of PmSTPS1 and PmSTPS2 in the biosynthesis pathway of P. minus, to produce aromatic sesquiterpenes.

Total synthesis of panicein A2.

The first total synthesis of the unusual aromatic sesquiterpene panicein A2 is reported and the structure of the natural product has been confirmed. When tested by the NCI against a range of human cancer cell lines, it was found that panicein A2 exhibits very little antiproliferative activity at 10 μM – an observation that is at odds with the earlier report that stated panicein A2 exhibits in vitro cytotoxicity against a number of tumour cell lines.

Production and Chemical Compounds of Gaharu Extract by Using Supercritical Fluid Extraction (SFE) of Unsoaked Gaharu at Different Pressure

Aquilaria species from the family of Thymelaeceae are the main source of gaharu, which has been classified as one of the most highly valuable, non-timber products in the world market. Currently, the method used for extracting gaharu essential oil is by using hydrodistillation. However, this method is inefficient where it produced low yield of oil with long time of extraction and thus increasing the production cost. To overcome this problem, the extraction of gaharu essential oil using Supercritical Fluid Extraction (SFE) with pressure 20MPa, 30MPa and 40MPa at 65 °C for 2 hours was studied. Result obtained after 2 hours of experiment was 0.6% of yield, which was higher compared to 0.2% yield of gaharu essential oil obtained via 3 days of hydrodistillation. After an extraction process, the product will be analyzed by using Gas Chromatography-Mass Spectrometry (GC-MS) to determine the chemical compounds and composition in the Gaharu SFE’s extract. Over eighteen to thirty-one compounds were identified in SFE extract compared with fifty-five identified in the hydrodistillated oil. The mutual occurrence of chemical compounds in all three samples in SFE was dimethyl phthalate, 8-epi-.gama.-eudesmol, diethyl Phthalate and 2-3-Butanediol. In comparison, the major compounds identified in hydrodistillated oil were 4-phenyl-2-butanone, jinkoh-eremol and α-guaiene (Saiful Nizam & Mashitah, 2010). There were certain aromatic sesquiterpenes compounds that were identified in this study, such as Globulol, Alloaromadendrene Naphthalene, 10s, 11s-Himachala-3(12), 4-diene, .delta.-Selinene and (-) - Aristolene.

Total Synthesis of (–)-HM-3 and (–)-HM-4 Utilizing a Palladium-Catalyzed Addition of an Arylboronic Acid to an Allenic Alcohol Followed by Eschenmoser–Claisen Rearrangement

The first asymmetric total synthesis of (–)-HM-3 and (–)-HM-4, aromatic sesquiterpenes isolated from the phytopathogenic fungus Helicobasidium mompa, has been achieved. Highlight of the synthesis is an enantiospecific construction of the quaternary carbon stereocenter utilizing a palladium-catalyzed addition of arylboronic acid to the allenic alcohol followed by Eschenmoser–Claisen rearrangement.

Optimization of Cat's Whiskers Tea (Orthosiphon stamineus) Using Supercritical Carbon Dioxide and Selective Chemotherapeutic Potential against Prostate Cancer Cells.

Cat's whiskers (Orthosiphon stamineus) leaves extracts were prepared using supercritical CO2 (SC-CO2) with full factorial design to determine the optimum extraction parameters. Nine extracts were obtained by varying pressure, temperature, and time. The extracts were analysed using FTIR, UV-Vis, and GC-MS. Cytotoxicity of the extracts was evaluated on human (colorectal, breast, and prostate) cancer and normal fibroblast cells. Moderate pressure (31.1 MPa) and temperature (60°C) were recorded as optimum extraction conditions with high yield (1.74%) of the extract (B2) at 60 min extraction time. The optimized extract (B2) displayed selective cytotoxicity against prostate cancer (PC3) cells (IC50 28 µg/mL) and significant antioxidant activity (IC50 42.8 µg/mL). Elevated levels of caspases 3/7 and 9 in B2-treated PC3 cells suggest the induction of apoptosis through nuclear and mitochondrial pathways. Hoechst and rhodamine assays confirmed the nuclear condensation and disruption of mitochondrial membrane potential in the cells. B2 also demonstrated inhibitory effects on motility and colonies of PC3 cells at its subcytotoxic concentrations. It is noteworthy that B2 displayed negligible toxicity against the normal cells. Chemometric analysis revealed high content of essential oils, hydrocarbon, fatty acids, esters, and aromatic sesquiterpenes in B2. This study highlights the therapeutic potentials of SC-CO2 extract of cat's whiskers in targeting prostate carcinoma.

Cyclopropyl Methyl Bromide–Mediated Gem-Diallylation: Total Synthesis of (±)-α-Cuparenone

The total synthesis of (±)-α-cuparenone, an aromatic sesquiterpene, has been described using the radical mediated gem-diallylation of substituted cyclopropyl methylbromide followed by ring-closing metathesis approach.

Calamenenes – aromatic bicyclic sesquiterpenes – from the Indian gorgonian Subergorgia reticulata (Ellis and Solander, 1786)

Three aromatic sesquiterpene derivatives, (+)-(7R, 10S)-2-methoxy calamenene (1), (+)-(7R, 10S)-2,5-dimethoxy calamenene (2) and (+)-(7R, 10S)-2-methoxy-5-acetoxy calamenene (3) were isolated from the methanol extract of the Indian gorgonian Subergorgia reticulata. Compound 2 has not been previously described in the literature. Compound 3 has not been isolated previously from a natural source. Compounds 1, 2 and 3 showed settlement inhibition activity against cyprids of Balanus amphitrite with EC50 values of 4.4, 7.8 and 0.03 µg mL−1, respectively. These compounds also exhibited considerable activity against Artemia nauplii at 50 µg mL−1, indicative of their potential use as cytotoxic agents.

Antimicrobial activity of the essential oil from the leaves of Croton cajucara Benth.

Croton cajucara Benth. (family Euphorbiaceae), locally known as „sacaca“, is a very important plant resource in the Amazon area, being used in folk medicine against gastrointestinal and liver disorders, diabetis and for cholesterol reduction. Several biological effects have been associated to cleordanes present in leaves and bark infusions [1]. A germplasm bank was established for agronomic studies of this species with individuals collected from different areas of the Amazon. Two morphotypes were identified, namely white sacaca and red sacaca. From chemical studies, the essential oils of these plants could be classified in two groups: one rich (up to 45%) in linalool [2], and other containing (up to 44%) of an aromatic sesquiterpene, isolated and identified by NMR as 7-hydroxycalamenene [3]. It was shown that the linalool rich oil is active against Leishmania amazonensis [4] and oral planktonic microorganisms [5]. Herein we present some results on the antimicrobial activity of the essential oil rich in 7-hydroxycalamenene. Minimum inhibitory concentration (MIC) was evaluated in triplicate according standard methods from the National Committee for Clinical Laboratory Standards (CLSi/NCCLS). Growing inhibition was observed for Mycobacterium smegmatis, M. tuberculosis (H37Rv), methicillin resistant Staphylococcus aureus (MRSA, BMB9393) and Rhizopus oryzae. The calculated MIC's were 156µg/mL for M. smegmatis, 4.9µg/mL for M. tuberculosis, 0.0012µg/mL for the MRSA and 0.15µg/mL for R. oryzae. From the bioautography test, the activity was associated to the presence of 7-hydroxycalamenene in the oil. The results observed were related to an essential oil containing 33% of 7-hydroxycalamenene.

Aromatic compounds from three Brazilian Lauraceae species

Phytochemical investigations on three Brazilian Lauraceae species from the Cerrado region of Sao Paulo State, Ocotea corymbosa (Meins) Mez., O. elegans Mez. and Persea pyrifolia Nees & Mart. ex Nees resulted in the isolation of flavonoids, an ester of the 4-O-E-caffeoylquinic acid, an aromatic sesquiterpene besides furofuran lignans. This is the first chemical study on the leaves of Ocotea elegans and O. corymbosa as well as the first report of non-volatile compounds from Persea pyrifolia.

The Chemistry and Cytotoxicity effects of Essential Oils of Leaves and Flowers of Albizia lebbeck (L.) Benth (Fabaceae) Growing in Nigeria

The chemical composition of the essential oil from the leaves and the flowers of Albizia lebbeck (L.) growing in Nigeria were studied using GC and GC-MS. The leaves oil contains 24 compounds which constituted about 91.2 % of the oil and was dominated by aromatic hydrocarbons (35.9 %), oxygenated monoterpenes (32.3 %), n-hydrocarbons (13.7 %), alkanals (8.1 %), and sesquiterpenes (0.4 %). The flowers oil contains 14 compounds which constituted about 96.2 % of the oil and was dominated by n-hydrocarbons (54.4 %), aromatic hydrocarbons (14.1 %), alkanals (13.2 %) and oxygenated monoterpenes (8.2 %). The cytotoxicity assay of the two oils against brine shrimp larvae gave LC50 = 0.5283 μg/mL (flowers) and 9.4507 μg/mL (leaves). Some of the identified compounds have not been reported in any previous literature known to us and hence novel.

Comparison of the Chemical Composition of the Essential Oil and the Water Soluble Oil of Baccharis dracunculifolia DC. (Asteraceae)

This study aimed to evaluate the chemical composition of Baccharis dracunculifolia essential oil and the water soluble oil obtained by steam distillation that were analyzed by GC and GC/MS. In the first hour of distillation B. dracunculifolia aerial parts yielded 0.08% oil and in the second hour, 0.27%. The oil recovered from the distillate water yielded 0.18 g/L in the first hour and 0.44 g/L in the second hour of distillation. The main volatile compounds identified in the distillate water were aromatic compounds and sesquiterpene alcohols.