Cyclic Terpenes Research Articles

Thermo-oxidative decomposition of lime, bergamot and cardamom essential oils

The thermal decomposition of three essential oils has been studied at 300 °C, using a 9% oxygen in nitrogen atmosphere, to mimic the thermal environment of flavours under low-temperature tobacco heating conditions. The starting compositions of the lime, bergamot and cardamom oils were determined by gas chromatography/mass spectrometry (GC/MS). The thermo-oxidative decomposition was evaluated by applying on-line pyrolysis-GC/MS. The main constituents of the oils studied were cyclic and linear monoterpenoids; however, the relative intensities of these components were characteristically different between oils. Lime oil was dominated by monoterpene hydrocarbons, while the other citrus oil, bergamot oil contained in addition a significant number of esters and alcohols. Oxygen-containing monoterpenoids were the dominant constituents of cardamom oil. The relative proportion of the constituents of all three essential oil samples significantly altered during oxidative pyrolysis at 300 °C. The strained rings of bicyclic monoterpenes (pinenes, sabinene, and thujene) underwent scission, resulting in the formation of monocyclic monoterpenes (limonene etc.). Both linear and cyclic terpene acetates decomposed via elimination of acetic acid, so linalyl acetate produced myrcene and ocimene, while terpinyl acetate formed mostly limonene and terpinolene. The relative intensities of linalool and eucalyptol were reduced during pyrolysis, which can be explained by dehydration reactions resulting in the formation of myrcene and ocimene, or limonene and terpinolene, respectively. The chemical reactions that occurred were explained by bond splitting and intramolecular rearrangement mechanisms, with oxygen playing a role in the initiation processes.

Biosynthetic studies on teleocidins in Streptomyces.

Teleocidin B, with its unique indolactam-terpenoid scaffold, is a potent activator of protein kinase C. This short review summarizes our recent research progress on the biosynthesis of teleocidins in Streptomyces blastmyceticus NBRC 12747. We first identified the biosynthetic genes for teleocidin B, which include genes encoding a non-ribosomal peptide synthetase (tleA), a cytochrome P450 monooxygenase (tleB), an indol prenyltransferase (tleC), and a C-methyltransferase (tleD). Notably, the tleD gene is located outside the tleABC cluster. Our in vivo and in vitro analyses revealed that TleD not only catalyzes the C-methylation of the prenyl chain but also produces the indole-fused cyclic terpene structure. This is the first report of terpene cyclization initiated by the C-methylation of the prenyl double bond. In contrast, TleC catalyzes the geranylation of the C-7 position of the indole ring, in the reverse fashion. Our X-ray crystallographic analyses provided the structural basis for the reverse prenylation reactions, and structure-based mutagenesis successfully resulted in the production of unnatural, novel prenylated indolactams.

Limonene dehydrogenase hydroxylates the allylic methyl group of cyclic monoterpenes in the anaerobic terpene degradation by Castellaniella defragrans

The enzymatic functionalization of hydrocarbons is a central step in the global carbon cycle initiating the mineralization of methane, isoprenes, and monoterpenes, the most abundant biologically produced hydrocarbons. Also, terpene-modifying enzymes have found many applications in the energy-economic biotechnological production of fine chemicals. Here, we describe a limonene dehydrogenase that was purified from the facultatively anaerobic betaproteobacterium Castellaniella defragrans 65Phen grown on monoterpenes under denitrifying conditions in the absence of molecular oxygen. The purified limonene:ferrocenium oxidoreductase activity hydroxylated the methyl group of limonene (1-methyl-4-(1-methylethenyl)-cyclohex-1-ene) yielding perillyl alcohol ([4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol). The enzyme had a DTT:perillyl alcohol oxidoreductase activity yielding limonene. Mass spectrometry and molecular size determinations revealed a heterodimeric enzyme comprising CtmA and CtmB. Recently, the two proteins had been identified by transposon mutagenesis and proteomics as part of the cyclic terpene metabolism (ctm) in C. defragrans and are annotated as FAD-dependent oxidoreductases of the protein domain family phytoene dehydrogenases and related proteins (COG1233). CtmAB is the first heterodimeric enzyme in this protein superfamily. Flavins in the purified CtmAB are oxidized by ferrocenium and are reduced by limonene. Heterologous expression of CtmA, CtmB, and CtmAB in Escherichia coli demonstrated that limonene dehydrogenase activity required both subunits, each carrying a flavin cofactor. Native CtmAB oxidized a wide range of monocyclic monoterpenes containing the allylic methyl group motif (1-methyl-cyclohex-1-ene). In conclusion, we have identified CtmAB as a hydroxylating limonene dehydrogenase and the first heteromer in a family of FAD-dependent dehydrogenases acting on allylic methylene or methyl CH-bonds. We suggest placing in Enzyme Nomenclature as new entry EC 1.17.99.8.

Norisoprenoids, Sesquiterpenes and Terpenoids Content of Valpolicella Wines During Aging: Investigating Aroma Potential in Relationship to Evolution of Tobacco and Balsamic Aroma in Aged Wine.

During wine aging, tobacco and balsamic aroma notes appear. In this paper, volatile compounds directly or potentially related to those aromas have been investigated in Corvina and Corvinone wines during aging. Corvina and Corvinone are two northern-Italy autochthonous red grape varieties, used to produce Valpolicella Classico and Amarone wines, both characterized by tobacco and balsamic aroma notes. Wines were analyzed shortly after bottling or following model aging at 60°C for 48, 72, and 168 h. Volatile compounds were analyzed by HS-SPME-GC-MS. Results showed that compounds related to tobacco aroma [β-damascenone, 3-oxo-α-ionol, (E)-1-(2,3,6-Trimethylphenyl)-buta-1,3-diene (TPB), and megastigmatrienones] increased in relationship to storage time with different patterns. β-Damascenone and 3-oxo-α-ionol rapidly increased to reach a plateau in the first 48–72 h of model aging. Instead, TPB and megastigmatrienones concentration showed a linear correlation with aging time. During model aging, several cyclic terpenes tended to increase. Among them 1,8-cineole and 1,4-cineole, previously reported to contribute to red wine eucalyptus notes increased proportionally to storage time, and this behavior was clearly associated with reactions involving α-terpineol, limonene, and terpinolene, as confirmed by studies with model wine solutions. Among other relevant volatile compounds, sesquiterpenes appear to contribute potentially balsamic and spicy aroma notes. In this study, linear sesquiterpenes (nerolidol, farnesol) underwent acid hydrolysis during long wine aging, while cyclic sesquiterpenes seemed to increase with time. The chemical pathways associated with evolution of some of the compounds investigated have been studied in model wine.

Forging C–C Bonds with Hindered Nucleophiles and Carbonyl Electrophiles: Reactivity and Selectivity of Allylic Tin Reagents/n-BuLi

Under activation with n-BuLi, trialkylstannanes containing crotyl-, geranyl-, and phenyldienylmethyl appendages were reacted with efficiency and selectivity to various ketone and enone electrophiles with low reactivity. The straightforward process gives access to tertiary alcohols that are vicinal to quaternary carbons. With α,α′-dimethoxy-γ-pyrone, on the other hand, the grafting of a dienyl side chain was effected to prepare dienyl α′-methoxy-γ-pyrone in a stereo- and regioselective and convergent manner. Furthermore, the advantages of this route were highlighted for the preparation of organolithium species at low temperature with the formation of a minimum amount of salts. Synthetic manipulations were demonstrated to illustrate the potential of the chemistry for constructing acyclic and cyclic terpene scaffolds.

Direct Probing of Criegee Intermediates from Gas-Phase Ozonolysis Using Chemical Ionization Mass Spectrometry.

Criegee intermediates (CIs), mainly formed from gas-phase ozonolysis of alkenes, are considered as atmospheric oxidants besides OH and NO3 radicals as well as ozone. Direct CI measurement techniques are inevitably needed for reliable assessment of CIs' role in atmospheric processes. We found that CIs from ozonolysis reactions can be directly probed by means of chemical ionization mass spectrometry with a detection limit of about 104-105 molecules cm-3. Results from quantum chemical calculations support the experimental findings. The simplest CI, CH2OO, is detectable as an adduct with protonated ethers, preferably with protonated tetrahydrofuran. Kinetic measurements yielded k(CH2OO + SO2) = (3.3 ± 0.9) × 10-11 and k(CH2OO + acetic acid) = (1.25 ± 0.30) × 10-10 cm3 molecule-1 s-1 at 295 ± 2 K, in very good agreement with recent measurements using diiodomethane photolysis for CH2OO generation. CIs from the ozonolysis of cyclohexene, acting as surrogate for cyclic terpenes, are followed as protonated species (CI)H+ using protonated amines as reagent ions. Kinetic investigations indicate a different reactivity of cyclohexene-derived CIs compared with that of simple CIs, such as CH2OO. It is supposed that the aldehyde group significantly influences the CI reactivity of the cyclohexene-derived CIs. The direct CI detection method presented here should allow study of the formation and reactivity of a wide range of different CIs formed from atmospheric ozonolysis reactions.

Aroma Profile of Galangal Composed of Cinnamic Acid Derivatives and Their Structure-Odor Relationships

Cinnamic acid derivatives are important odorants due to their characteristic scent. Some fragrance materials, such as cinnamon bark, matsutake mushrooms, and Kaempferia galanga L. rhizome (galangal), contain several cinnamic acid derivatives as important odor constituents. The main odor constituent of glangal is (E)-ethyl 4-methoxycinnamate, but the odor of this compound is different from that of galangal. We investigated the aroma profile of galangal using our previously described method that considers the intermolecular interactions of the odorant compounds with their receptors. Odorant compounds in galangal were extracted by hexane extraction, steam distillation, and headspace sampling. The odor of the hexane extract was different from that of the steam - distillate and similar to that of galangal; therefore, we searched for the key compounds contributing to the aroma profile of galangal by separating the constituents of the hexane extract. A fraction with a galangal-like odor was obtained by bulb-to-bulb distillation of the hexane extract. The main component of this fraction was not (E)-ethyl 4-methoxycinnamate, but rather ethyl cinnamate. These results indicate that ethyl cinnamate is more important in the aroma profile of galangal than (E)-ethyl 4-methoxycinnamate. GC-MS analysis revealed that this fraction contained aromatic compounds, cyclic terpenes, and linear chain compounds in addition to ethyl cinnamate. We synthesized cinnamic acid derivatives and examined the importance of the odor expression of these cinnamic acid derivatives. Cinnamic acid derivatives lacking a p-methoxy group had a strong fruity odor. Replacement of the hydrogen atom at the para position with a methoxy group altered and weakened the odor. We found that a p-methoxy group in cinnamic acid derivatives plays an important role in the aroma profile of galangal.

Measurement of volatile organic compounds (VOCs) in libraries and archives in Florence (Italy)

Indoor air samples from libraries and archives in Florence, Italy, were collected and analysed for a variety of volatile organic compounds. The aim was to perform a characterisation of the indoor air quality, and try to elucidate if there are VOCs that may cause or result from the determination of the cultural heritage institutions.All compounds of interest were regularly detected, with BTEXs (Benzene, Toluene, Ethylbenzene, Xylenes) being the most abundant and followed by cyclic volatile methylsiloxanes, aldehydes, terpenes and organic acids. The prevalence and qualitative characteristics, such as concentrations, profiles and indoor/outdoor ratios of BTEXs underline the important influence of the outdoor air infiltrations on the indoor air concentrations. Acetic acid that is a substance that can oxidise books and other exposed objects was detected at concentrations ranging between 1.04 and 18.9μgm−3, while furfural, that is a known marker of paper degradation, was constantly present at concentrations that ranged between 5.26 and 32.6μgm−3.This work shows the importance that indoor air quality monitoring campaigns can have in order to give early warning to cultural heritage institution managers about the impact that indoor air quality can have on exposed and/or preserved objects.

Biomimetic Total Synthesis of Hyperjapones A–E and Hyperjaponols A and C

AbstractHyperjapones A–E and hyperjaponols A–C are complex natural products of mixed aromatic polyketide and terpene biosynthetic origin that have recently been isolated from Hypericum japonicum. We have synthesized hyperjapones A–E using a biomimetic, oxidative hetero‐Diels–Alder reaction to couple together dearomatized acylphloroglucinol and cyclic terpene natural products. Hyperjapone A is proposed to be the biosynthetic precursor of hyperjaponol C through a sequence of: 1) epoxidation; 2) acid‐catalyzed epoxide ring‐opening; and 3) a concerted, asynchronous alkene cyclization and 1,2‐alkyl shift of a tertiary carbocation. Chemical mimicry of this proposed biosynthetic sequence allowed a concise total synthesis of hyperjaponol C to be completed in which six carbon–carbon bonds, six stereocenters, and three rings were constructed in just four steps.

Biomimetic Total Synthesis of Hyperjapones A-E and Hyperjaponols A and C.

Hyperjapones A-E and hyperjaponols A-C are complex natural products of mixed aromatic polyketide and terpene biosynthetic origin that have recently been isolated from Hypericum japonicum. We have synthesized hyperjapones A-E using a biomimetic, oxidative hetero-Diels-Alder reaction to couple together dearomatized acylphloroglucinol and cyclic terpene natural products. Hyperjapone A is proposed to be the biosynthetic precursor of hyperjaponol C through a sequence of: 1) epoxidation; 2) acid-catalyzed epoxide ring-opening; and 3) a concerted, asynchronous alkene cyclization and 1,2-alkyl shift of a tertiary carbocation. Chemical mimicry of this proposed biosynthetic sequence allowed a concise total synthesis of hyperjaponol C to be completed in which six carbon-carbon bonds, six stereocenters, and three rings were constructed in just four steps.

Catalytic Coupling of Carbon Dioxide with Terpene Scaffolds: Access to Challenging Bio-Based Organic Carbonates.

The challenging coupling of highly substituted terpene oxides and carbon dioxide into bio-based cyclic organic carbonates catalyzed by Al(aminotriphenolate) complexes is reported. Both acyclic as well as cyclic terpene oxides were used as coupling partners, showing distinct reactivity/selectivity behavior. Whereas cyclic terpene oxides showed excellent chemoselectivity towards the organic carbonate product, acyclic substrates exhibited poorer selectivities owing to concomitant epoxide rearrangement reactions and the formation of undesired oligo/polyether side products. Considering the challenging nature of these coupling reactions, the isolated yields of the targeted bio-carbonates are reasonable and in most cases in the range 50-60 %. The first crystal structures of tri-substituted terpene based cyclic carbonates are reported and their stereoconnectivity suggests that their formation proceeds through a double inversion pathway.

Physical Processing and Emission Characteristics of Firelogs from Cotton Ginning Byproducts

Cotton burr with stems (CBS), a byproduct from cotton ginning operations was evaluated for its suitability in firelogs. Firelog burn quality was examined by varying the CBS to paraffin wax ratio, and firelog processing conditions. The firelogs were burned in a wood stove to quantify the burn quality, burn time, product durability, and gaseous emissions. Firelog composition had no effect on the burn temperatures. Carbon monoxide (CO), ammonium (NH4), hydrogen (H2), and nitrous oxide (NO) gases were not detected in the gaseous emissions. Air emission samples from combustion showed the presence of n-alkanes, n-alkenes, oxygenated volatile organic compounds, polycyclic aromatic hydrocarbons (PAH), halogenated alkane, cyclic terpenes, benzene derivatives and naphthalene. Overall this study showed the potential of CBS as an alternative material for manufacturing firelogs.

ChemInform Abstract: Recent Progress in Sustainable Polymers Obtained from Cyclic Terpenes: Synthesis, Properties, and Application Potential

AbstractReview: [131 refs.

Limonene inhibits streptococcal biofilm formation by targeting surface-associated virulence factors.

The present study explores the efficacy of limonene, a cyclic terpene found in the rind of citrus fruits, for antibiofilm potential against species of the genus Streptococcus, which have been deeply studied worldwide owing to their multiple pathogenic efficacy. Limonene showed a concentration-dependent reduction in the biofilm formation of Streptococcus pyogenes (SF370), with minimal biofilm inhibitory concentration (MBIC) of 400 μg ml - 1. Limonene was found to possess about 75-95 % antibiofilm activity against all the pathogens tested, viz. Streptococcus pyogenes (SF370 and 5 clinical isolates), Streptococcus mutans (UA159) and Streptococcus mitis (ATCC 6249) at 400 μg ml - 1 concentration. Microscopic analysis of biofilm architecture revealed a quantitative breach in biofilm formation. Results of a surface-coating assay suggested that the possible mode of action of limonene could be by inhibiting bacterial adhesion to surfaces, thereby preventing the biofilm formation cascade. Susceptibility of limonene-treated Streptococcus pyogenes to healthy human blood goes in unison with gene expression studies in which the mga gene was found to be downregulated. Anti-cariogenic efficacy of limonene against Streptococcus mutans was confirmed, with inhibition of acid production and downregulation of the vicR gene. Downregulation of the covR, mga and vicR genes, which play a critical role in regulating surface-associated proteins in Streptococcus pyogenes and Streptococcus mutans, respectively, is yet further evidence to show that limonene targets surface-associated proteins. The results of physiological assays and gene expression studies clearly show that the surface-associated antagonistic mechanism of limonene also reduces surface-mediated virulence factors.

Recent progress in sustainable polymers obtained from cyclic terpenes: synthesis, properties, and application potential.

The functionalization and polymerization of biobased monocyclic terpenes and their derivatives for the synthesis of sustainable polymers is described, especially in view of the synthetic routes and properties of the obtained macromolecular architectures. Comparison of these procedures and the obtained materials with "classical" oil-based approaches, and also with alternative biobased routes, gives interesting insights into the potential of these small terpene building-block structures for modern polymer science and technology.

Emergence of terpene cyclization in Artemisia annua.

The emergence of terpene cyclization was critical to the evolutionary expansion of chemical diversity yet remains unexplored. Here we report the first discovery of an epistatic network of residues that controls the onset of terpene cyclization in Artemisia annua. We begin with amorpha-4,11-diene synthase (ADS) and (E)-β-farnesene synthase (BFS), a pair of terpene synthases that produce cyclic or linear terpenes, respectively. A library of ~27,000 enzymes is generated by breeding combinations of natural amino-acid substitutions from the cyclic into the linear producer. We discover one dominant mutation is sufficient to activate cyclization, and together with two additional residues comprise a network of strongly epistatic interactions that activate, suppress or reactivate cyclization. Remarkably, this epistatic network of equivalent residues also controls cyclization in a BFS homologue from Citrus junos. Fitness landscape analysis of mutational trajectories provides quantitative insights into a major epoch in specialized metabolism.

Impacts of nucleotide fixation during soybean domestication and improvement

BackgroundPlant domestication involves complex morphological and physiological modification of wild species to meet human needs. Artificial selection during soybean domestication and improvement results in substantial phenotypic divergence between wild and cultivated soybeans. Strong selective pressure on beneficial phenotypes could cause nucleotide fixations in the founder population of soybean cultivars in quite a short time.ResultsAnalysis of available sequencing accessions estimates that ~5.3 million single nucleotide variations reach saturation in cultivars, and then ~9.8 million in soybean germplasm. Selective sweeps defined by loss of genetic diversity reveal 2,255 and 1,051 genes were involved in domestication and subsequent improvement, respectively. Both processes introduced ~0.1 million nucleotide fixations, which contributed to the divergence of wild and cultivated soybeans. Meta-analysis of reported quantitative trait loci (QTL) and selective signals with nucleotide fixation identifies a series of putative candidate genes responsible for 13 agronomically important traits. Nucleotide fixation mediated by artificial selection affected diverse molecular functions and biological reactions that associated with soybean morphological and physiological changes. Of them, plant-pathogen interactions are of particular relevance as selective nucleotide fixations happened in disease resistance genes, cyclic nucleotide-gated ion channels and terpene synthases.ConclusionsOur analysis provides insights into the impacts of nucleotide fixation during soybean domestication and improvement, which would facilitate future QTL mapping and molecular breeding practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12870-015-0463-z) contains supplementary material, which is available to authorized users.

Oxidation of Terpenoids with a Cyclohexanone Fragment by Performic Acid

Performic acid is a reactive, inexpensive, and available reagent for Baeyer–Villager oxidation of ketones that is used infrequently in the chemistry of cyclic terpene ketones, e.g., only for the oxidation of isocaranone [1] and allobetulone [2]. The goal of the present work was to expand the scope of this reagent for the oxidation of terpenoids with a cyclohexanone fragment. We found that Baeyer–Villager oxidation of 28-oxoallobetulin-3-one (1), carvomenthone (2), and menthone (3) by performic acid occurred regioand stereospecifically to give lactones 5–7, respectively. Oxidation of isomenthone (4) by H2O2–HCOOH caused racemization of the asymmetric center with the isopropyl substituent (probably due to keto–enol tautomerism under acidic conditions) to give a mixture of diastereomeric lactones 7 and 8 (1:1), in contrast with diastereospecific m-chloroperbenzoic acid [3].

The oxygen-independent metabolism of cyclic monoterpenes in Castellaniella defragrans 65Phen.

BackgroundThe facultatively anaerobic betaproteobacterium Castellaniella defragrans 65Phen utilizes acyclic, monocyclic and bicyclic monoterpenes as sole carbon source under oxic as well as anoxic conditions. A biotransformation pathway of the acyclic β-myrcene required linalool dehydratase-isomerase as initial enzyme acting on the hydrocarbon. An in-frame deletion mutant did not use myrcene, but was able to grow on monocyclic monoterpenes. The genome sequence and a comparative proteome analysis together with a random transposon mutagenesis were conducted to identify genes involved in the monocyclic monoterpene metabolism. Metabolites accumulating in cultures of transposon and in-frame deletion mutants disclosed the degradation pathway.ResultsCastellaniella defragrans 65Phen oxidizes the monocyclic monoterpene limonene at the primary methyl group forming perillyl alcohol. The genome of 3.95 Mb contained a 70 kb genome island coding for over 50 proteins involved in the monoterpene metabolism. This island showed higher homology to genes of another monoterpene-mineralizing betaproteobacterium, Thauera terpenica 58EuT, than to genomes of the family Alcaligenaceae, which harbors the genus Castellaniella. A collection of 72 transposon mutants unable to grow on limonene contained 17 inactivated genes, with 46 mutants located in the two genes ctmAB (cyclic terpene metabolism). CtmA and ctmB were annotated as FAD-dependent oxidoreductases and clustered together with ctmE, a 2Fe-2S ferredoxin gene, and ctmF, coding for a NADH:ferredoxin oxidoreductase. Transposon mutants of ctmA, B or E did not grow aerobically or anaerobically on limonene, but on perillyl alcohol. The next steps in the pathway are catalyzed by the geraniol dehydrogenase GeoA and the geranial dehydrogenase GeoB, yielding perillic acid. Two transposon mutants had inactivated genes of the monoterpene ring cleavage (mrc) pathway. 2-Methylcitrate synthase and 2-methylcitrate dehydratase were also essential for the monoterpene metabolism but not for growth on acetate.ConclusionsThe genome of Castellaniella defragrans 65Phen is related to other genomes of Alcaligenaceae, but contains a genomic island with genes of the monoterpene metabolism. Castellaniella defragrans 65Phen degrades limonene via a limonene dehydrogenase and the oxidation of perillyl alcohol. The initial oxidation at the primary methyl group is independent of molecular oxygen.

Concerted Cyclization of Lanosterol C-Ring and D-Ring Under Human Oxidosqualene Cyclase Catalysis: An ab Initio QM/MM MD Study.

Human oxidosqualene cyclase (OSC) is one key enzyme in the biosynthesis of cholesterol. It can catalyze the linear-chain 2,3-oxidosqualene to form lanosterol, the tetracyclic (6-6-6-5 members for A-B-C-D rings) cholesterol precursor. It also has been treated as a novel antihyperlipidemia target. In addition, the structural diversity of cyclic terpenes in plants originates from the cyclization of 2,3-oxidosqualene. The enzyme catalytic mechanism is considered to be one of the most complicated ones in nature, and there are a lot of controversies about the mechanism in the past half a century. Herein, state-of-the-art ab initio QM/MM MD simulations are employed to investigate the detailed cyclization mechanism of C-ring and D-ring formation. Our study reveals that the C and D rings are formed near-synchronously from a stable "6-6-5" ring intermediate. Interestingly, the transition state of this concerted reaction presents a "6-6-6" structure motif, while this unstable "6-6-6" structure in our simulations is thought to be a stable intermediate state in most previous hypothetical mechanisms. Furthermore, as the tailed side chain of 2,3-oxidosqualene shows a β conformation while it is α conformation in lanosterol, finally, it is observed that the rotatable "tail" chain prefers to transfer β conformation to α conformation at the "6-6-5" intermediate state.