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Sterostreins A–E (1, 2, 3a/3b, 4, and 5), five novel terpenoids, were isolated from cultures of the mushroom fungus Stereum ostreaBCC 22955. Sterostrein A (1) exhibited antimalarial activity (IC502.3 μg/mL) and cytotoxicity (IC505.3–38 μg/mL). [ABSTRACT FROM AUTHOR]

The first enantioselective synthesis of (−)-jiadifenin (1), a potent neurite outgrowth promoter isolated from the Illiciumspecies, is described. The synthetic strategy builds upon bicyclic motif 6, which represents the AB ring of the natural product and proceeds in 19 steps and 1.1% overall yield. Key to our approach is a Mn(III)-mediated oxidation reaction of A ring that, following a regio- and diastereoselective α-hydroxylation and methylation sequence, produces the desired functionalities of (−)-jiadifenin. The effect of synthetic 1in NGF-mediated neurite outgrowth was also measured in PC-12 cells. [ABSTRACT FROM AUTHOR]

Many terpenes used as fragrance compounds autoxidize when exposed to air, forming allylic hydroperoxides that have the potential to be skin contact allergens. To trigger the immunotoxidty process that characterizes contact allergy, these hydroperoxides are supposed to bind covalently to proteins in the skin via radical pathways. We investigated the formation of reactive radical intermediates from 7-hydroperoxy3,7-dimethylocta-1,5-dien-3-ol and 2-hydroperoxylimonene, responsible for the sensitizing potential acquired by au toxidized linalool and limonene. Both compounds were synthesized through new short and reproducible synthetic pathways. The hydroperoxide decomposition catalyzed by Fe(II)/Fe(III) redox systems, playing a key role in degradating peroxides in vivo, was examined by spin-trapping-EPR spectroscopy. Alkoxyl and carbon-centered free radicals derived from the hydroperoxides were successfully trapped by the spin-trap 5,5-dimethyl-1-pyrroline N-oxide, whereas peroxyl radicals were characterized by spin-trapping studies with 5-diethoxyphosphoryI-5-methyl-1-pyrroline N-oxide. Using liquid chromatography combined with mass spectrometry, we demonstrated the formation of adducts, via radical mechanisms induced by Fe(II)/Fe(III), between the hydroperoxides and Nacetylhistidine methyl ester, a model ammo acid that is prone to radical reactions. Free radicals derived from these hydroperoxides can thus induce amino acid chemical modifications via radical mechanisms. The study of these mechanisms will help to understand the sensitizing potential of hydroperoxides. [ABSTRACT FROM AUTHOR]

Three new briarane diterpenoids, briareolate esters L–N (1–3), have been isolated from a gorgonian Briareum asbestinum. Briareolate esters L (1) and M (2) are the first natural products possessing a 10-membered macrocyclic ring with a (E,Z)-dieneone and exhibit growth inhibition activity against both human embryonic stem cells (BG02) and a pancreatic cancer cell line (BxPC-3). Briareolate ester L (1) was found to contain a “spring-loaded” (E,Z)-dieneone Michael acceptor group that can form a reversible covalent bond to model sulfur-based nucleophiles. [ABSTRACT FROM AUTHOR]

Schicagenins A–C (1–3), three unprecedented nortriterpenoids characterized with a tetracyclic oxa-cage motif and C9side chain, were discovered from the leaves and stems of Schisandra chinensis. Their structures were determined on the basis of extensive spectroscopic analysis, and the absolute stereochemistries were established by single-crystal X-ray diffraction and CD experiments. A plausible biosynthetic pathway of 1–3was also discussed. [ABSTRACT FROM AUTHOR]

Nonactivated trienes and aryltrienes were cyclized into polycyclic compounds in good to excellent yields under bismuth triflate catalysis in a biomimetic fashion. The reaction showed broad applicability and allowed for the formation of functionalized bicyclic to tetracyclic structures from simple precursors in one pot. For some specific substrates, the cyclization was followed by a methyl shift as encountered in terpenoid biosynthesis. [ABSTRACT FROM AUTHOR]

In this study, mono- and pentacyclic C35 terpenes from Bacillus subtilis were biosynthesized via the cyclization of C35 isoprenoid using purified enzymes, including the first identified new terpene cyclase that shows no sequence homology to any of the known terpene cyclases. On the basis of these findings, we propose that these C35 terpenes should be called the new family of "sesquarterpenes." [ABSTRACT FROM AUTHOR]

The first total synthesis of the unique terpene rippertenol, a molecule with dense stereochemical complexity arrayed on a compact framework largely devoid of functional groups, is described. Key elements include orchestrated and unique applications of aldol condensations, Diels-Alder chemistry, and a ring expansion to advance a chiral starting material containing a single chiral center into the final target in a concise and diastereocontrolled manner. [ABSTRACT FROM AUTHOR]

This article presents research targeted toward the isolation and detection of unique molecular structures from what is believed to be the world's most complex organic mixture: dissolved organic matter (DOM). Hydrophilic interaction chromatography (HILIC) was used to separate Suwannee River DOM (SRDOM) into 80 fractions, simplified to the extent that detection with nuclear magnetic resonance spectroscopy (NMR) results in many sharp signals that are indicative of individual compounds, some of which are identifiable with multidimensional NMR. Parallel factor analysis (PARAFAC) of fluorescence excitation-emission matrices (EEMs) was additionally employed on HILIC-simplified fractions to further confirm the effectiveness of the HILIC separations as well as draw insight into how structural characteristics relate to DOM fluorescence signals. Findings suggest that material believed to be derived from both cyclic and linear terpenoids was dominant in the most hydrophobic fractions as were the majority of the fluorescence signals, whereas hydrophilic material was highly correlated with carbohydrate-type structures as well as high contributions from amino acid fluorescence. NMR spectra of DOM, typically featureless mounds, are substantially more detailed with HILIC-simplified fractions to the point where hundreds of signals are present and 2D NMR correlations permit significant structural identifications. [ABSTRACT FROM AUTHOR]

Six novel monoterpene chromane esters were isolated from the aerial parts of Peperomia obtusifolia (Piperaceae) using chiral chromatography. This is the first time that chiral chromane esters of this kind, ones with a tethered chiral terpene, have been isolated in nature. Due to their structural features, it is not currently possible to assess directly their absolute stereochemistry using any of the standard classical approaches, such as X-ray crystallography, NMR, optical rotation, or electronic circular dichroism (ECD). Herein we report the absolute configuration of these molecules, involving four chiral centers, using vibrational circular dichroism (VCD) and density functional theory (DFT) (B3LYP/6-31G*) calculations. This work further reinforces the capability of VCD to determine unambiguously the absolute configuration of structurally complex molecules in solution, without crystallization or derivatization, and demonstrates the sensitivity of VCD to specify the absolute configuration for just one among a number of chiral centers. We also demonstrate the sufficiency of using the so-called inexpensive basis set 6-31G* compared to the triple-ζ basis set TZVP for absolute configuration analysis of larger molecules using VCD. Overall, this work extends our knowledge of secondary metabolites in plants and provides a straightforward way to determine the absolute configuration of complex natural products involving a chiral parent moiety combined with a chiral terpene adduct. [ABSTRACT FROM AUTHOR]

As a result of a combined theoretical and experimental study, we describe a two-step protocol for the preparation of an optically pure, multifunctional, cyclopentanic core shared by a number of natural products. This process is based on a hitherto unreported Ti (III)-mediated diastereoselective cyclization in which the hydroxy-directed template effect played by the Ti (III) species was found to be crucial for the stereoselective outcome of the reaction. The viability of this concept was confirmed with the first protecting-group free synthesis of three enantiopure chokols, namely, chokols K, E, and B. [ABSTRACT FROM AUTHOR]

Two novel sesterterpenoids, leucosceptroids C (1) and D (2), possessing unusual antipodal cyclopentenones while maintaining the stereochemistry and functionality of the tricyclic cores, were discovered from the leaves of Leucosceptrum canum(Labiatae). Their structures including absolute stereochemistries were determined by comprehensive NMR, MS, and single-crystal X-ray diffraction analyses. The potent antifeedant activity of 1against the generalist plant-feeding insect Helicoverpa armigera(EC50= 0.017 μmol/cm2) suggested them to be new defensive sesterterpenoids of L. canum. [ABSTRACT FROM AUTHOR]

Three novel triterpenoids, henrischinins A−C (1−3), featuring the unique motif of a 3-one-2-oxabicyclo[3.2.1]-octane, were isolated from the leaves and stems of Schisandra henryi. Their structures were elucidated by spectroscopic methods, and the absolute configuration of 2was confirmed by a single crystal X-ray diffraction. Compounds 1and 2showed weak cytotoxicity against HL-60 cell lines. [ABSTRACT FROM AUTHOR]

Two new sesterterpenoids, phorbasones A (1) and B (2), were isolated from the Korean marine sponge Phorbassp. Their complete structures were elucidated by spectral data and chemical reactions. Phorbasone A exhibited a positive effect on the calcium deposition activity in C3H10T1/2 cells. The biogenic origin of the core structure is believed to be through a novel rearrangement from the ansellone carbon structure. [ABSTRACT FROM AUTHOR]

A short, stereoselective approach to the fused tricyclic carbon skeleton found in the tigliane and daphnane classes of diterpene natural products is described. Convergent coupling of the A- and C-rings, followed by diastereoselective cerium enolate addition and formation of a double acetal set the stage for generation of an oxonium ylide via a transient metallocarbene. An efficient Stevens [1,2]-shift furnished the 7-membered B-ring, possessing the bridgehead oxygenation pattern found in the natural systems. [ABSTRACT FROM AUTHOR]

Duboscic acid (1), a triterpenoid with a unique carbon backbone, was isolated from Duboscia macrocarpaBocq. It is the first member of a new class of triterpenoids, for which the name “dubosane” is proposed. Duboscic acid has a potent α-glucosidase inhibition, and its structure was unambiguously deduced by a single-crystal X-ray diffraction study. [ABSTRACT FROM AUTHOR]

A biomimetic total synthesis of (±)-rossinone B has been achieved through a highly efficient strategy featuring a series of rationally designed reactions, including a one-pot allylic rearrangement/oxidation reaction to generate the vinyl quinone 27, an intramolecular vinyl quinone Diels−Alder reaction to construct the linear 6−6−5 tricyclic core of 28, and a double conjugate addition/β-elimination cascade to complete the total synthesis of 1. [ABSTRACT FROM AUTHOR]

Twenty marine-engine lubricants from five Japanese oil companies were discriminated on the basis on a hopane analysis using a gas chromatograph−mass spectrometer (GC−MS). The hopane ratios of 18α-22,29,30-trisnorneohopane (1) to 17α-22,29,30-trisnorhopane (2) and of 17α-21β(H)-norhopane (3) to 17α-21β(H)-hopane (5) were determined. Each lubricant can be discriminated by combining the figures represented by the 1to 2and 3to 5ratios and principal component analysis from 1through (22R)-17α-21β(H)-29-pentakishomohopane (15). Oleanane (4), one of the biomarkers inherent in the crude oils from Southeast Asia, has been detected in the lubricants of eight out of 20 types, and 4represents a significant feature for the discrimination. The discrimination of the lubricants in the spilled oils was also investigated. [ABSTRACT FROM AUTHOR]

The mechanism of the reaction of the sulfur dioxide (SO2) with four stabilized Criegee intermediates (stabCI−CH3−OO, stabCI−OO, stabCIx−OO, and stabCH2OO) produced via the ozonolysis of limonene have been investigated using ab initio and DFT (density functional theory) methods. It has been shown that the intermediate adduct formed by the initiation of these reactions may be followed by two different reaction pathways such as H migration reaction to form carboxylic acids and rearrangement of oxygen to produce the sulfur trioxide (SO3) from the terminal oxygen of the COO group and SO2. We found that the reaction of stabCI−OO and stabCH2OO with SO2can occur via both the aforementioned scenarios, whereas that of stabCI−CH3−OO and stabCIx−OO with SO2is limited to the second pathway only due to the absence of migrating H atoms. It has been shown that at the CCSD(T)/6-31G(d) + CF level of theory the activation energies of six reaction pathways are in the range of 14.18−22.59 kcal mol−1, with the reaction between stabCIx−OO and SO2as the most favorable pathway of 14.18 kcal mol−1activation energy and that the reaction of stabCI−OO and stabCH2OO with SO2occurs mainly via the second reaction path. The thermochemical analysis of the reaction between SO2and stabilized Criegee intermediates indicates that the reaction of SO2and stabilized Criegee intermediates formed from the exocyclic primary ozonide decomposition is the main pathway of the SO3formation. This is likely to explain the large (∼100%) difference in the production rate in the favor of the exocyclic compounds observed in recent experiments on the formation of H2SO4from exocyclic and endocyclic compounds. [ABSTRACT FROM AUTHOR]

Chemical analysis of a marine-derived Streptomycessp. (CMB-M0423) isolated from beach sand off Heron Island, Australia, yielded three new members of the rare pyrroloterpene biosynthetic structure class. Identified by detailed spectroscopic analysis as the first reported examples of naturally occurring 2-nitropyrroles, heronapyrroles A−C (1−3) displayed promising biological activitywith low to submicromolar IC50activity against Gram-positive bacteria but no cytotoxicity toward mammalian cell lines. [ABSTRACT FROM AUTHOR]

Psiguadials A (1) and B (2), two novel sesquiterpenoid-diphenylmethane meroterpenoids with unusual skeletons, along with a pair of known epimers, psidial A (3) and guajadial (4), were isolated from the leaves of Psidium guajava. Their structures with absolute configurations were elucidated by means of NMR, X-ray diffraction, and quantum chemical CD calculation. Compounds 1, 2, and 4exhibited potent inhibitory effects on the growth of human hepatoma cells. [ABSTRACT FROM AUTHOR]

Although there are many reagent combinations that can initiate polyene cyclizations, simple electrophilic halogen sources have not yet proven broadly effective as promoters of such processes. Herein is described a readily prepared and stable class of reagents capable of effecting such transformations for a wide range of electron-rich and -deficient terpenes derived from geraniol, farnesol, and nerol, thereby enabling the effective synthesis of a diverse array of complex chlorine-, bromine-, and iodine-containing polycyclic frameworks. Efforts to date have led to the first racemic laboratory total synthesis and structural revision of the anti-HIV natural product peyssonol A as well as an efficient and concise inaugural total synthesis of peyssonoic acid A. They have also permitted formal racemic total syntheses of aplysin-20, loliolide, K-76, and stemodin to be achieved through routes that are typically shorter, higher-yielding, and more environmentally conscious than previous efforts. Preliminary attempts to use chiral forms of the reagent class for enantioselective alkene halogenation are also described. [ABSTRACT FROM AUTHOR]

We measured the solubility in supercritical carbon dioxide (CO2) of farnesol [(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol] and naringenin [(2S)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one] using a static-analytic method (a high-pressure static equilibrium cell coupled to an HPLC). The molar fraction of farnesol in the saturated CO2-rich phase increased between y2= 0.13·10−3at 333 K and 11.4 MPa to y2= 1.91·10−3at 333 K and 26.0 MPa for farnesol and from y2= 0.49·10−5at 313 K and 10.3 MPa to y2= 1.65·10−5at 333 K and 44.5 MPa for naringenin. The average error of our measurements was about 25 %. Farnesol had an end-temperature crossover point at approximately 17 MPa, whereas naringenin exhibited a monotonous increase in solubility with both temperature and pressure. The differences in solubility between farnesol, naringenin, and other sesquisterpenes or flavonoids reported in the literature were partially explained by differences in molecular weight and polarity between solutes. We correlated experimental data as a function of the system temperature and pressure and the density of the solvent using a literature model that also showed the autoconsistency of the data for CO2densities above 412 kg·m−3for naringenin. [ABSTRACT FROM AUTHOR]

Terpene synthascs are responsible for a large diversity of terpene carbon skeletons found in nature. The multiproduct sesquiterpene synthase MtTPS5 isolated from Medicago truncatula produces 27 products from farnesyl diphosphate (1, FDP). In this paper, we report the reaction steps involved in the formation of these products using incubation experiments with deuterium-containing substrates; we determined the absolute configuration of individual products to establish the stereochemical course of the reaction cascade and the initial conformation of the cycling substrate. Additional labeling experiments conducted with deuterium oxide showed that cadalane sesquitcrpenes are mainly produced via the protonation of the neutral intermediate germacrene D (5). These findings provide an alternative route to the general accepted pathway via nerolidyl diphosphate (2, NDP) en route to sesquiterpenes with a cadalane skeleton. Mutational analysis of the enzyme demonstrated that a tyrosine residue is important for the protonation process. [ABSTRACT FROM AUTHOR]

We are reporting the first total synthesis of the tetracyclic terpene natural product cryptoacetalide. Key steps of the synthesis are a microwave-mediated [2+2+2] cyclotrimerization reaction to construct the central benzcne ring, and a light-mediated radical cyclization to assemble the spiro-ketal moiety. [ABSTRACT FROM AUTHOR]

Alkene ozonolysis reactions proceed through an unstable intermediate, the primary ozonide (POZ). POZ decomposition controls the complex mechanism. We probe the kinetics of primary ozonide decomposition using temperature programmed reaction spectroscopy (TPRS), revealing primary ozonide decomposition barrier heights of 9.1 ± 0.4, 9.4 ± 0.4, and 11.9 ± 1.2 kcal mol−1for cyclohexene, 1-methyl-cyclohexene, and methylene-cyclohexane, respectively. We compare experimental decomposition spectra with spectral predictions using density functional theory (DFT) to reveal decomposition products resembling vinyl-hydroperoxides and dioxiranes. We do not find evidence of secondary ozonides. Additional computations with DFT, scaled with the TPRS barrier height, yield barrier heights ranging from 9.4 to 12.1 kcal mol−1for the four competing decomposition pathways of the 1-methyl-cyclohexene POZ. Entropic differences were minimal, indicating that POZ decomposition branching is controlled purely by enthalpic variations. These kinetic computations were used to calculate a hydroxyl radical yield for 1-methyl-cyclohexene ozonolysis of 0.85 at 298 K. [ABSTRACT FROM AUTHOR]

Cytosporolides A−C (1−3), three caryophyllene-derived meroterpenoids with a unique peroxylactone skeleton, were isolated from cultures of the fungus Cytosporasp. Their structures were elucidated by NMR spectroscopy, and the absolute configuration of the 5,6-diol moiety in 1was assigned using Snatzke’s method. Compounds 1−3showed significant antimicrobial activity against the Gram-positive bacteria Staphylococcus aureusand Streptococcus pneumoniae. [ABSTRACT FROM AUTHOR]

Ansellone A (1) has been isolated from the dorid nudibranch Cadlina luteomarginataand the sponge Phorbassp. It has the new “ansellane” sesterterpenoid carbon skeleton, and it activates the cAMP signaling pathway. [ABSTRACT FROM AUTHOR]

A stereocontrolled approach for the construction of ABC ring systems of micrandilactone A and lancifodilactone G has been developed. The synthesis involves construction of an enantiopure functionalized cycloheptene derivative 17 through RCM of the dienol 14 prepared from the known o- mannitol-derived unsaturated ester 12. A remarkable regioselectivity during hydroboration of the cycloheptene derivative 17 was observed during its transformation to the cycloheptanone 20. RCM of the diene 24 prepared stereoselectively from 20 gave the spiro-dihydrofuran 25. The ketal unit in 25 was then converted into the carbinols 28 and 36. A bromonium ion initiated highly stereocontrolled intramolecular etherification in 28 and 37 led to the tricyclic ethers 29 and 38, respectively. Reductive removal of bromine from 29 and 38 followed by RuO4 oxidation led to the furo-furanone derivatives 31 and 40, the C-5-epi ABC ring systems of the schisandra nortriterpenoids 1 and 2. [ABSTRACT FROM AUTHOR]

A biosynthetically inspired synthesis of ()-liphagal has been achieved from ()-sclareolide in 13 steps (9% overall yield). The key step is a biomimetic ring expansion of a highly stabilized benzylic carbocation, which generates the seven-membered ring and the benzofuran of the natural product in a single cascade reaction. [ABSTRACT FROM AUTHOR]

Emissions of biogenic volatile organic compounds (BVOCs) are important precursors to both ozone and secondary organic aerosol formation. In this study, we identify and quantify volatile (C10) and intermediate-volatility (C15) BVOCs stored in and emitted from 22 prominent woody and herbaceous crops with a particular focus on sesquiterpenoids (SQTs), which have presented measurement challenges in previous studies. Monoterpenoids (MNTs) and SQTs were simultaneously emitted from all the crops studied; there were significant correlations between emission rates and leaf content for both MNTs and SQTs and additional correlations between MNTs and SQTs in both emissions and leaf content. Our results suggest that species with high concentrations of stored terpenoids in their leaves, such as those grown commercially for their essential oil content, are likely high BVOC emitters. Emissions from agricultural species were dominated by SQTs at low MNT emission rates (on the order of several tens of ng/(gDM∙h)), while at higher MNT levels (on the order of several hundreds of ng/(gDM∙h)), SQT emissions were approximately equivalent. Based on our empirical correlations, we estimate that global SQT emissions are similar to MNT emissions and on the order of 100 Tg yr-1, which justifies the need for better representation of SQTs in both BVOC emission and atmospheric models. [ABSTRACT FROM AUTHOR]

The simplest form of terpenoid chemistry is found for the monoterpenes, which give plants fragrance, flavor, and medicinal properties. Monoterpene synthases employ geranyl diphosphate as a substrate to generate an assortment of cyclic products. In the current study we present a detailed analysis of the multiple gas-phase reaction pathways in the synthesis of bornyl cation from geranyl diphosphate. Additionally, the fate of the proposed bornyl cation intermediate in the bornyl diphosphate synthase reaction is investigated by molecular dynamics simulations. We employ accurate density functional theory (DFT) methods after careful validation against high-level ab initio data for a set of model carbocations. The gas-phase results for the monoterpene reactions indicate a diverging reaction mechanism with multiple products in the absence of enzymatic control. This complex potential energy surface includes several possible bifurcation points due to the presence of secondary cations. Additionally, the suggested bornyl cation intermediate in the bornyl diphosphate synthase reaction is studied by molecular dynamics simulations employing a hybrid quantum mechanics (DFT)-molecular mechanics potential energy function. The simulations suggest that the bornyl cation is a transient species as in the gas phase and that electrostatic steering directs the formation of the final product, bornyl diphosphate. [ABSTRACT FROM AUTHOR]

The X-ray crystal structure of recombinant epi-isozizaene synthase (EIZS). a sesquiterpene cyclase from Streptomyces coelicolor A3(2), has been determined at 1.60 Å resolution. Specifically, the structure of wild-type EIZS is that of its closed conformation in complex with three Mg2+ ions, inorganic pyrophosphate (PPi), and the benzyltriethylammonium cation (HTAC). Additionally, the structure of D99N EIZS has been determined in an open, ligand-free conformation at 1.90 Å resolution. Comparison of these two structures provides the first view of conformational changes required for substrate binding and catalysis in a bacterial terpenoid cyclase. Moreover, the binding intertctions of BTAC may mimic those of a carbocation intermediate in catalysis. Accordingly, the aromatic rings of F95, F96, and F198 appear to be well-oriented to stabilize carbocation intermediates in the cyclization cascade through cation-π interactions. Mutagenesis of aromatic residues in the enzyme active site results in the production of alternative sesquiterpene product arrays due to altered modes of stabilization of carbocation intermediates as well its altered templates for the cyclization of farnesyl diphosphate. Accordingly, the 1.64 Å resolution crystal structure of F198A EIZS in complex with three Mg2+ ions, PPi and BTAC reveals an alternative binding orientation of BTAC; alternative binding orientations of a carbocation intermediate could lead to the formation of alternative products. Finally, the crystal structure of wild-type EIZS in a complex with four Hg2+ ions has been determined at 1.90 Å resolution, showing that metal binding triggers a significant conformational change of helix G to cap the active site. [ABSTRACT FROM AUTHOR]

The reactivity of two new bicyclic cyclohexenones (13and 27) with several Nazarov reagents is presented. A flexible synthetic strategy is developed and provides access to highly substituted tricycles related to quassinoids and triterpenes. [ABSTRACT FROM AUTHOR]

The atmospheric oxidation of monoterpenes plays a central role in the formation of secondary organic aerosols (SOAs), which have important effects on the weather and climate. However, models of SOA formation have large uncertainties. One reason for this is that SOA formation depends directly on the vapor pressures of the monoterpene oxidation products, but few vapor pressures have been reported for these compounds. As a result, models of SOA formation have had to rely on estimated values of vapor pressure. To alleviate this problem, we have developed the concatenated gas saturation method, which is a simple, reliable, high-throughput method for measuring the vapor pressures of low-volatility compounds. The concatenated gas saturation method represents a significant advance over traditional gas saturation methods. Instead of a single saturator and trap, the concatenated method uses several pairs of saturators and traps linked in series. Consequently, several measurements of vapor pressure can be made simultaneously, which greatly increases the rate of date collection. It also allows for the simultaneous measurement of a control compound, which is important for ensuring data quality. In this paper we demonstrate the use of the concatenated gas saturation method by determination of the vapor pressures of five monoterpene oxidation products and n-tetradecane (the control compound) over the temperature range 283.15-313.15 K. Over this temperature range, the vapor pressures ranged from about 0.5 Pa to about 70 Pa. The standard molar enthalpies of vaporization or sublimation were determined by use of the Clausius-Clapeyron equation. [ABSTRACT FROM AUTHOR]

Three new sesterterpenoids, phorbaketals A (1), B (2), and C (3) which have a spiroketal of the hydrobenzopyran moiety, were isolated from the Korean marine sponge Phorbassp. Their complete structures were elucidated by spectral and chemical methods. They exhibited moderate cytotoxicity against human colorectal, hepatoma, and lung cancer cell lines. Furthermore, the cultivation of the bacterial fraction from the sponge afforded compound 1. [ABSTRACT FROM AUTHOR]

We previously reported that [[N-[3β-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betulinic acid derivatives were synthesized, and some of them displayed selective anti-HIV-2 activity at nanomolar concentrations. In comparison to compounds with anti-HIV-1 activity, a shorter C-28 side chain is required for optimal anti-HIV-2 activity. [ABSTRACT FROM AUTHOR]

The new sesterterpenoids alotaketals A (1) and B (2) have been isolated from extracts of the marine sponge Hamigerasp. collected in Papua New Guinea. Their chemical structures were elucidated by analysis of spectroscopic data. Alotaketals A and B have the unprecedented alotane carbon skeleton, and they activate the cAMP cell signaling pathway with EC50’s of 18 and 240 nM, respectively. [ABSTRACT FROM AUTHOR]

Dehydroeburicoic acid (DeEA) is a triterpene purified from medicinal fungi such as Antrodia camphorate, the crude extract of which is known to exert cytotoxic effects against several types of cancer cells. We aim to test the hypothesis that DeEA possesses significant cytotoxic effects against glioblastomas, one of the most frequent and malignant brain tumors in adults. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays indicated that DeEA inhibited the proliferation of the human glioblastoma cell U87MG. In addition, Annexin V and propidium iodide staining showed that DeEA treatment led to a rapid increase of glioblastomas in the necrotic/late apoptotic fraction, whereas cell cycle analysis revealed that DeEA failed to significantly enhance the population of U87MG cells in the hypodiploid (sub-G1) fraction. Using electron microscopy, we found that DeEA induced significant cell enlargements, massive cytoplasmic vacuolization, and loss of mitochondrial membrane integrity. DeEA treatment triggered an intracellular Ca2+increase, and DeEA-induced cell death was significantly attenuated by BAPTA-AM but not ethylenediaminetetraacetic acid or ethylene glycol tetraacetic acid. DeEA instigated a reduction of both mitochondrial transmembrane potential and intracellular ATP level. Moreover, DeEA induced proteolysis of α-spectrin by calpain, and DeEA cytotoxicity in U87MG cells was caspase-independent but was effectively blocked by calpain inhibitor. Interestingly, DeEA also caused autophagic response that was prevented by calpain inhibitor. Taken together, these results suggest that in human glioblastomas, DeEA induces necrotic cell death that involves Ca2+overload, mitochondrial dysfunction, and calpain activation. [ABSTRACT FROM AUTHOR]

Two new terpenoids, capillosanol (1) and chabranol (2), possessing unprecedented terpenoid skeletons, were isolated from the soft corals Sinularia capillosaand Nephthea chabroli, respectively. The structures of 1and 2were elucidated through extensive spectroscopic analyses. The cytotoxicities of these compounds were tested in vitro. [ABSTRACT FROM AUTHOR]

Diastereoselective Birch reduction—alkylation reactions of bicyclic β-alkoxy-α,β-unsaturated carbonyl compounds and tricyclic analogues were investigated. Although the relative configuration of the product was altered according to the structure of the starting material, stereoselectivity of the reaction could be accounted for by similar reaction pathways. The product from the tricyclic β-alkoxy-α,β-unsaturated carbonyl compound corresponded to the trichothecene skeleton. [ABSTRACT FROM AUTHOR]

The article focuses on microbial biotransformation methods of producing monoterpenoid and norisoprenoid natural flavor compounds and other approaches of terpene oxidation. It reveals the use of integer cells from plant-cultured cells, fungi and yeasts, and bacteria, of purified enzymes, and of unconventional biocatalysts in biotransformation processes. Moreover, it discloses genetic modifications, plants recombinant enzymes, as well as cloning and expression of terpene biotransforming agents.

In this work the effect of the overall flow rate of the biphasic reaction mixture on hydrogenation distribution products is reported. As it was already presented by us, the reaction rate strongly correlates with the phase equilibrium existing in the system. On the other hand, carbon dioxide is nonreactive; nevertheless by its presence it changes the energy balance. The catalytic performance in four kinds of overall flow rate conditions (1.3, 3.3, 5.3, and 7.3 mL/min) was compared under fixed hydrogen (2.5 MPa) and total pressure (12.5 MPa). The appearance of isomers of limonene and partially hydrogenated products significantly rely upon the flow rate used in the reaction. The 1% Pd SCN catalyst used in the reaction gave the final products trans- and cis-p-menthane in a 2/3to 1/3molar ratio. [ABSTRACT FROM AUTHOR]

Nine esters of a naturally occurring triterpenoid, arjunolic acid (from Terminalia arjuna), with alkyl chains have been synthesized, and their self-assembly has been studied in organic liquids. All of the esters examined were found to be excellent gelators. No birefringence was detected in optical micrographs of the transparent toluene gels with 5% (w/w) ethyl arjunolate or 5% (w/w) p-nitrobenzyl arjunolate as the gelator, but a spherulitic-type pattern was seen for a gel of 1.2% (w/w) p-nitrobenzyl arjunolate in 1/1 (w/w) chloroform/cyclohexane. Electron microscope images revealed self-assembled fibrillar network (SAFIN) structures with right-handed helical ribbons in some gels. With increasing concentration of the gelators, the gel-to-sol transition temperature (Tgel) increased and then approached plateau values. Differential scanning thermograms demonstrated that the heats for transition from transparent gels to sols of ethyl arjunolate or p-nitrobenzyl arjunolate in toluene are very small. Powder X-ray diffractograms revealed that the molecular packing in the SAFINof the 5% (w/w) ethyl arjunoate in the toluene gel was amorphous and similar to the diffractogram recorded for the neat gelator. Although the diffractogram of neat p-nitrobenzyl arjunolate consisted of broad peaks, suggesting disordered packing, the low-angle peaks of the corresponding toluene gel were much sharper; these results indicate more crystalline packing in the SAFINthan in the neat gelator. The kinetics and growth of the transformation of sols of p-nitrobenzyl arjunolate in 1/1 (w/w) chloroform/cyclohexane to their gels have been investigated at different incubation temperatures by circular dichroism spectroscopy. The data have been analyzed to probe the mechanism of SAFINformation and the relationship between the molecular structures of the esters of arjunolic acid and their abilities to function as gelators of a wide variety of organic liquids. [ABSTRACT FROM AUTHOR]

Twenty-four new sesterterpenes, compounds 1−24, were isolated from the aerial parts of Salvia dominica. Their structures were elucidated by 1D and 2D NMR experiments as well as ESIMS analysis and chemical methods. The evaluation of the biological activity of Salvia dominicasesterterpenes by means of a panel of chemical and biological approaches, including chemical proteomics, surface plasmon resonance (SPR) measurements, and biochemical assays were realized. Obtained results showed that 18 out of the 24 sesterterpene lactones isolated from Salvia dominicainteract with tubulin−tyrosine ligase (TTL) an enzyme involved in the tyrosination cycle of the C-terminal of tubulin, and inhibit TTL activity in cancer cells. Besides, results of our studies provided an activity/structure relationship that can be used to design effective TTL inhibitors. [ABSTRACT FROM AUTHOR]

The triterpene product profile is reported for At5g36150 (PEN3), the last unexamined oxidosqualene cyclase in the reference plant Arabidopsis thaliana. PEN3 makes tirucalla-7,24-dien-3β-ol (∼85%) and several minor products. Also discussed are the unexpectedly facile convergent evolution of another Arabidopsistirucalladienol synthase (LUP5), mechanistic origins of the 20Sconfiguration, and active-site remodeling necessary to accommodate the 17α side chain. This work marks the first completed functional characterization of all triterpene synthases in a higher plant. [ABSTRACT FROM AUTHOR]

The CYP51 lanosterol 14α-demethylases are evolutionarily ancient enzymes ubiquitously distributed throughout the biological domains. The experimental X-ray crystal structure of Mycobacterium tuberculosis(Mtb) CYP51 is the first of an enzyme capable of catalyzing inert C−C bond cleavage. Amino acid sequence comparisons of CYP51 family members with other members of the CYP superfamily reveal the almost universally conserved “acid-alcohol” pair, putatively involved in proton transport and O2activation, is replaced with a His-Thr dyad. In this study, extended molecular dynamics (MD) simulations and hybrid quantum mechanics/molecular mechanics calculations (QM/MM) are applied to characterize reactive oxygen intermediates and to unravel mechanisms of O2activation vis-à-visproton transport for this important enzyme. MD confirms stable His259δH+-Thr260OH−O2(Mtbnumbering) hydrogen bonding early in the simulations, suggesting these amino acids could function similarly to the Asp251-Thr252 pair in CYP101. QM/MM calculations support this dyad competently catalyzes the peroxo to Compound 0 (Cmpd 0) reaction, albeit an endothermic homolytic O−O scission mechanism affording Compound I (Cmpd I) was identified. Disruption of the His259H+-Thr260OH hydrogen bond in MD simulation divulges a second previously unidentified hydrogen-bond network, including three water molecules linking Glu173 in the CYP51 F-helix to the distal O2atom. Expansion of the QM region to contain these atoms unveils an unprecedented triradicaloid electronic structure of the peroxo intermediate characterized by spin polarization to the Glu173 side chain, attributable to the protein electrostatic environment. This amino acid, in concert with an active-site water network, catalyzes a facile protonation of the peroxo intermediate and offers a series of redundant heterolytic and homolytic mechanisms, affording exothermic formation of the ultimate oxidant Cmpd I. In summary, this study highlights the importance of the protein electrostatic environment to tune the electronic structure of CYP catalytic intermediates in addition to Cmpd I and illustrates the diversity of proton transport pathways available to these enzymes to drive catalysis. [ABSTRACT FROM AUTHOR]

In a continuing study of potent anti-HIV agents, seventeen 28,30-disubstituted betulinic acid (BA, 1) derivatives and seven novel 3,28-disubstituted BA analogues were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, compound 21showed an improved solubility and equal anti-HIV potency (EC50= 0.09 μM) when compared to HIV entry inhibitors 3b(IC9564, (3R,4S)-N′-[N-[3β-hydroxy-lup-20(29)-en-28-oyl]-8-aminooctanoyl]-4-amino-3-hydroxy-6-methylheptanoic acid) and 4(A43-D, [[N-[3β-O-(3′,3′-dimethylsuccinyl)-lup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane). Using a cyclic secondary amine to form the C-28 amide bond increased the metabolic stability of the derivatives significantly in pooled human liver microsomes. The most potent compounds 47and 48displayed potent anti-HIV activity with EC50values of 0.007 and 0.006 μM, respectively. These results are slightly better than that of bevirimat (2, 3′,3′-dimethylsuccinylbetulinic acid), which is currently in phase IIb clinical trials. Compounds 47and 48should serve as attractive promising leads to develop next generation, metabolically stable, 3,28-disubstituted bifunctional HIV-1 inhibitors as clinical trials candidates. [ABSTRACT FROM AUTHOR]

Chamber studies to quantify formation yields of oxygenated organic reaction products were performed for gas-phase reactions of the hydroxyl radical (OH·) and ozone (O3) with the common cleaning product terpene compounds limonene, α-terpineol, and geraniol. The reaction products observed were identified and quantified using derivatization by O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and gas chromatography/mass spectrometry. Limonene rate constants and product mechanisms have been examined previously. Several of these investigations have measured product yields from limonene reactions and those results are compared with the results presented here. Although rate constants and product mechanisms have previously been investigated for α-terpineol and geraniol, yields of oxygenated organic reaction products have not been measured. Reactions from the fragrance compounds in this study produced several dicarbonyl reaction products such as glyoxal, methylglyoxal, and 4-oxopentanal which were observed from all three terpenes. Total carbonyl yields ranged from 5.1% for the limonene + O3 reaction to 92% for the geraniol + O3 reaction. [ABSTRACT FROM AUTHOR]

The total synthesis of (+)-paeonisuffrone starting from (+)- 10-hydroxycarvone is described. The key step of our synthetic strategy is a titanium-catalyzed stereoselective cyclization initiated by epoxide opening through electron transfer. This reaction stereoselectively affords the highly oxygenated pinane skeleton present in the target molecule and opens a new and effective approach to the synthesis of the complex, biologically active terpenoids isolated from the roots of the Chinese paeony (Paeonia albiflora Pallas and Paeonia suffruticosa Andrews). [ABSTRACT FROM AUTHOR]