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Macrophorins are representative examples of isoprenoid epoxycyclohexenones containing cyclized drimane moieties. We located and characterized the biosynthetic gene cluster of macrophorin from Penicillium terrestris. MacJ encoded by this cluster was characterized to be the first example of a membrane-bound type-II terpene cyclase catalyzing the cyclization of meroterpenoids via direct protonation of the terminal olefinic bond in acyclic yanuthones. The late-stage functionalization and substrate promiscuity of MacJ make it a potential biocatalyst for the synthesis of macrophorin analogues. [ABSTRACT FROM AUTHOR]

The pool of abundant chiral terpene building blocks (i.e., "chiral pool terpenes") has long served as a starting point for the chemical synthesis of complex natural products, including many terpenes themselves. As inexpensive and versatile starting materials, such compounds continue to influence modern synthetic chemistry. This review highlights 21st century terpene total syntheses which themselves use small, terpene-derived materials as building blocks. An outlook to the future of research in this area is highlighted as well. [ABSTRACT FROM AUTHOR]

Wickerol A (1) is an unusual diterpene with remarkable activity against the H1N1 influenza virus. Its tetracyclic skeleton contains three quaternary carbons and is marked by several syn-pentane interactions which force a six-membered ring into a twist-boat conformation. We present an asymmetric synthesis of wickerol A (1) that is based on a Jung Diels-Alder reaction, an intramolecular alkylation to complete the 6-5-6-6 ring system, and a conjugate addition, all of which overcome considerable steric strain. During the synthesis, we isolated an unexpected cyclopropane that presumably stems from a carbonium ion intermediate. [ABSTRACT FROM AUTHOR]

The structurally intriguing terpenes pallambins C and D have been assembled in only 11 steps from a cheap commodity chemical: furfuryl alcohol. This synthesis, which features a redox-economic approach free of protecting-group manipulations, assembles all four-ring systems via a sequential cyclization strategy. Of these fourring constructing operations, two are classical (Robinson annulation and Mukaiyama aldol) and two are newly devised. During the course of this work a method for the difunctionalization of enol ethers was developed, and the scope of this transformation was explored. [ABSTRACT FROM AUTHOR]

The nitrate radical (NO3) is the dominant nighttime oxidant in most urban and rural environments and reacts rapidly with biogenic volatile organic compounds toform secondary organic aerosol (SOA) and organic nitrates (ON). Here, we study the formation of SOA and ON from the NO3 oxidation of two monoterpenes (α-pinene and β-pinene) and investigate how they evolve during photochemical aging. High SOA mass loadings are produced in the NO3+β-pinene reaction, during which we detected 41 highly oxygenated gas- and particle-phase ON possessing 4 to 9 oxygen atoms. The fraction of particle-phase ON in the β-pinene SOA remains fairly constant during photochemical aging. In contrast to the NO3+β-pinene reaction, low SOA mass loadings are produced during the NO3+α-pinene reaction, during which only 5 highly oxygenated gas- and particle-phase ON are detected. The majority of the particle-phase ON evaporates from the α-pinene SOA during photochemical aging, thus exhibiting a drastically different behavior from that of β-pinene SOA. Our results indicate that nighttime ON formed by NO3+monoterpene chemistry can serve as either permanent or temporary NOx sinks depending on the monoterpene precursor. [ABSTRACT FROM AUTHOR]

Terpenoid spiroethers are abundant natural flavors with significant impact, particularly in the food industry. We present in this article the synthesis of new derivatives of the well-known flavors theaspirane and vitispirane using a variant of the Prins cyclization starting from α,β-unsaturated or heterocyclic ketones. When aromatic ketones were used as the starting materials for Lewis acid-mediated cyclizations, an alternative pathway involving a domino sequence of Prins cyclization, followed by an intramolecular Friedel--Crafts alkylation, gave benzoannelated oxabicyclo[3.3.1]nonane derivatives. Different reaction pathways may be triggered by the reaction temperature to give with good selectivity either tetrahydropyran derivatives as conventional Prins products or oxabicyclo[3.3.1]nonane derivatives. [ABSTRACT FROM AUTHOR]

Triterpenoids comprise a very diverse family of polycyclic molecules that is well-known to possess a myriad of medicinal properties. Therefore, triterpenoids constitute an attractive target for medicinal chemistry and diversity-oriented synthesis. Photochemical transformations provide a promising tool for the rapid, green, and inexpensive generation of skeletal diversity in the construction of natural product-like libraries. With this in mind, we have developed a diversity-oriented strategy, whereby the parent triterpenoids bryonolic acid and lanosterol are converted to the pseudosymmetrical polyketones by sequential allylic oxidation and oxidative cleavage of the bridging double bond at the B/C ring fusion. The resultant polyketones were hypothesized to undergo divergent Norrish-Yang cyclization to produce unique 6/4/8-fused triterpenoid analogues. The subtle differences between parent triterpenoids led to dramatically different spatial arrangements of reactive functionalities. This finding was rationalized through conformational analysis to explain unanticipated photoinduced pinacolization, as well as the regio- and stereochemical outcome of the desired Norrish-Yang cyclization. [ABSTRACT FROM AUTHOR]

Relative kinetic techniques have been used to measurethe ratecoefficients for the reactions of oxygenated terpenes (menthol, borneol,fenchol, camphor, and fenchone) and cyclohexanol with hydroxyl radicals(OH) and chlorine atoms (Cl) at 298 ± 2 K and atmospheric pressure.The rate coefficients obtained for the reactions of the title compoundswith OH are the following (in units of 10–11cm3molecule–1s–1): (1.48± 0.31), (2.65 ± 0.32), (2.49 ± 0.30), (0.38 ±0.08), (0.39 ± 0.09) for menthol, borneol, fenchol, camphor,and fenchone, respectively. For the corresponding reactions with Clatoms the rate coefficients are as follows (in units of 10–10cm3molecule–1s–1): (3.21 ± 0.26), (3.40 ± 0.28), (2.72 ± 0.13), (2.93± 0.17), (1.59 ± 0.10), and (1.86 ± 0.29) for cyclohexanol,menthol, borneol, fenchol, camphor, and fenchone, respectively. Thereported error is twice the standard deviation. Product studies ofthe reactions were performed using multipass in situ FTIR (Fouriertransform infrared spectroscopy) and solid-phase microextraction (SPME)with analysis by GC–MS (gas chromatography–mass spectrometry).A detailed mechanism is proposed to justify the observed reactionproducts. [ABSTRACT FROM AUTHOR]

The autoxidation of geranial with O2was studied both experimentally and using density functional theory. Computational results were used to interpret experimentally observed product ratios. Geranial was found to autoxidize, forming 6,7-epoxygeranial as the main oxidation product. Hydroperoxides corresponding to those identified as important skin sensitizers in previous studies of fragrance terpenes could not be detected. Instead, a dioxolan derivative and its corresponding hydroperoxide were identified and detected in high concentrations. The distribution of products in autoxidation generally depends on the stabilities of the intermediate peroxyl radicals. In this study, the formation of a peracyl radical was found to be highly favored. This radical forms peracid which epoxidizes geranial. The epoxide thus produced can react with acyl radical to yield the dioxolan hydroperoxide. The dioxolan derivative is believed to form in an acid catalyzed closed shell reaction between 6,7-epoxygeranial and geranial. The dioxolan hydroperoxide and 6,7-epoxygeranial are strong sensitizers and are considered to be the compounds mainly responsible for the skin sensitization potency of air-exposed geranial. [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]

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]

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 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 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]

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]

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]

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]

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]

The kinetics of limonene epoxidation catalyzed by PW-Amberlite under triphasic conditions is described. A mechanistic pathway was postulated, and a heterogeneous kinetic model was derived following pseudo-stationary-state theory. Using adsorption parameters that were estimated from independent binary adsorption experiments, the resulting kinetic model fitted the experimental data quite well. [ABSTRACT FROM AUTHOR]

An efficient access to 2-isobetulin, 2-isobetulinic acid, 2-isooleanolic acid, and 2-isoursolic acid has been developed. The key step is a novel one-pot conversion of 2,3-dihydroxy triterpenes to 3-deoxy-2-oxo triterpenes. This method provides a new access to 3-deoxy-2-substituted pentacyclic triterpenes as potential therapeutic agents against metabolic diseases, tumors, and HIV infection. [ABSTRACT FROM AUTHOR]

A general preparation method of the all-(E)-polyprenols 12 has been developed from readily available geranyl sulfone by the chain-extension process utilizing the C5 unit 5 and the chain-termination process utilizing the C5 unit 10 together with the chemoselective reductive desulfonylation. The polyprenols 12 were converted to compounds 3 containing two consecutive prenyl sulfone moieties at the tail end, which underwent the controlled electrophilic cyclization only at the carbon-carbon double bonds that were remote from the flat and rigid benzenesulfonyl groups. [ABSTRACT FROM AUTHOR]

A unified strategy for the chemical synthesis of the icetexane diterpenoids brussonol and 5,6-dihydro-6-hydroxysalviasperanol has led to a structural revision of the recently isolated natural products abrotandiol and abrotanone. [ABSTRACT FROM AUTHOR]

The reaction of natural product derived propargylic alcohols with CpCo(CO)2 produces three new types of natural product hybrids having two or three terpene or steroid fragments. The tether joining the natural product subunits is built during the reaction. Type 1 hybrids have two terpene or steroid moieties joined by a CpCo-cyclobutadiene tether, with the two units disposed in a 1,2-arrangement (9, 14, 22). Type 2 hybrids have a Co-cyclopentadienone tether (10). Type 3 has three units of terpene or steroid joined to a benzene ring (11, 12, 15). An unusual Co-mediated β-carbon elimination pathway of propargylic alcohols leading to ketones (an unknown process in this chemistry) has been observed. [ABSTRACT FROM AUTHOR]

The first total synthesis of an (E)-cladiellin diterpene, (-)-cladiella-6,11-diene-3-ol (1), was accomplished featuring an intramolecular amide enolate alkylation-intramolecular Diels-Alder strategy. In addition, a highly stereo-, regio-, and chemoselective synthetic strategy for other members of the cladiellin diterpenes such as (+)-polyanthellin A (2), (-)-cladiell-11-ene-3,6,7-triol (3), and (-)-deacetoxyalcyonin acetate (4) was developed utilizing the synthetic (E)-cladiellin 1 as a common intermediate by taking advantage of the unique chemical properties of its C(6)-(E)-oxatricyclic skeleton. [ABSTRACT FROM AUTHOR]

Total syntheses of two new (±)-kempane derivatives 30 and 47 were achieved with transannular Diels-Alder reaction (TADA) serving as the key step for the stereoselective formation of tricyclic [6.6.5J system 3. This synthetic approach also reveals that the geometry of the C3 group of such a tricyclic system plays an important role for the formation of the seven-membered kempane skeleton. [ABSTRACT FROM AUTHOR]

The complex 8 of isopinocampheylborane and p-(dimethyl-amino)pyridine (DMAP) can be obtained with >99% ee starting from α-pinene with 80–90% ee by hydroboration using DMAP·BH3 (5) activated by 5% iodine, or by the conventional hydroboration of α-pinene, followed by addition of DMAP. Purification of the air-stable 8 is readily accomplished by crystallization from methanol. Conversion of 8 into the trifluoroborate adduct 1 using KHF2 occurs without erosion of ee. Generation of the derived 2 in situ with TMSC1 as the fluorophile also occurs with little, if any, loss of ee, as evidenced by the preparation of the salicaldimine complex 11 and the derived amino alcohol 12 with 94% ee overall. [ABSTRACT FROM AUTHOR]

Regioselective halogenation of the terminal isopropylidene unit of different acyclic polyolefinic polyprenoids (farnesyl acetate, geranylgeranyl acetate, squalene, etc.) using NCS/catalytic polymer-supported selenenyl bromide is described; good to excellent yields are obtained (68–96%). The first applications of this protocol include the concise synthesis of bioactive terpenoids 1–3. [ABSTRACT FROM AUTHOR]

The biosynthesis of geosmin (1) and (1(10)E,5E)-germacradien-11-ol (2), two volatile terpenoid compounds emitted by the myxobacteria Myxococcus xanthus and Stigmatella aurantiaca, was investigated in feeding experiments with different labeled precursors. In these experiments, the volatiles released by the cell cultures grown on agar plates were collected with a closed-loop stripping apparatus (CLSA) and analyzed by GC-MS. [²H10]Leucine and [4,4,4,5,5,5-²H6]dimethylacrylate were fed to wild-type strains and bkd mutant strains, which are impaired in the degradation of leucine to isovaleryl-CoA. [²H10]Leucine was incorporated into 1 and 2 only by the wild-type strains via the biosynthetic pathway that involves leucine degradation and branching into the mevalonate pathway. Dimethylacrylyl-CoA (DMA-CoA) is an intermediate in the leucine degradation and in the recently discovered pathway from HMG-CoA to isovaleryl-CoA. The corresponding free acid, [4,4,4,5,5,5-²C;H6]dimethylacrylic acid, was incorporated into 1 and 2 only by the mutants impaired in leucine degradation. [4,4,6,6,6-²H5]Mevalonic acid lactone (12) was synthesized and fed to M. xanthus and S. aurantiaca wild-type strains and a double mutant strain of M. xanthus. This strain does not degrade leucine and is impaired in the reduction of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid. The mass spectral analysis of labeled 1 and 2 obtained in these feeding experiments led to a biosynthetic scheme to 1 with intermediate 2. This pathway differs from that observed in the liverwort Fossombronia pusilla and thus suggests microbial geosmin biosynthesis following a route different from that in liverworts. Our results are supported by a 1,2-hydride shift of the tertiary hydrogen atom at C-4a into the ring opposite to that in F. pusilla. [ABSTRACT FROM AUTHOR]

We describe a novel convergent procedure that has proved useful in the synthesis of a wide range of meroterpenoid-related structures containing a mono-, ses- qui-, or diterpenoid moiety linked to a nonfused aromatic subunit with various substitution patterns. The key steps were the Stille-type coupling of aryl stannanes and allylic carbonates, followed by the titanocene-catalyzed domino cyclization of aryl epoxypolyprenes. The coupling reaction was perfectly compatible with preformed epoxides, while the sequential cyclization, which presumably proceeded via alkyl radicals inert to benzene derivatives, selectively provided exocyclic alkenes. [ABSTRACT FROM AUTHOR]

A novel terpenoid-related compound, stolonilactone (1), was isolated from the Okinawan soft coral Clavularia koellikeri. The structure of I was elucidated on the basis of spectroscopic analysis. A possible biogenesis of 1 through the [4 + 2]-cycloaddition of a trisnorsesquiterpenoid-type diene and a cembranolide-type dienophile is proposed. [ABSTRACT FROM AUTHOR]

An asymmetric total synthesis of (+)-chatancin was achieved via a transannular Diels-Alder (TADA) reaction of an in situ generated macrocyclic pyranophane pseudobase. The presented route constitutes the second of two proposed biosynthetic pathways that involves a TADA reaction. It links this diterpene biogenetically to the cembranoids. A set of TADA selection rules that rationalize the formation of (+)-chatancin from a dynamic equilibrium of four 2-hydroxy-2H-pyrane bicycles and their 16 potential TADA transition states are also outlined. Beyond the TADA reaction, highlights of the synthetic work include the assembly of a chiral acyclic macrocyclization substrate from (S)-citronellol and an efficient macrocyclization via a β-ketosulfoxyde/enone Michael addition. [ABSTRACT FROM AUTHOR]

Examines the solid-state 13C chemical shift tensors in terpenes using nuclear magnetic resonance (NMR) analyses. Evidence of mixed polymorphic forms in solid verbenol; Structural predictions from computed and experimental NMR shift tensors; Characterization of the minor polymorphic form of verbenol.

Presents the results of a study in which the reaction between NO... and ...pinene has been studied in large reaction chambers of 0.5-200m... volume, using long path FT-IR, GC-ECD, and GC-FID for the analyses. Description of the reaction from a chemical perspective; Presentation of the first quantitative identification of pinonaldehyde and alkylnitrates from the reaction of pinonaldehyde in the system.

Extension of anion relay chemistry (ARC) beyond the area of dithianes has been achieved by the design of two effective ARC linchpins capable of three- and four-component couplings. To showcase the ARC tactic in natural product synthesis, a cytotoxic gorgonian linear sesquiterpene was constructed, and the absolute configuration assigned via the Kakisawa/Mosher method. The synthesis proceeded in five steps with an overall yield of 22%. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effect of 1-deoxy-xylulose-5-phosphate (DXP) reductoisomerase-catalyzed reaction through a secondary kinetic isotope. It explores the evidence for a retroaldol-aldol rearrangement. Under the study, terpenoids are biosynthesized with two 5-carbon isoprene units, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP).

The article discusses a study which demonstrates that the substitution of an Ile for Thr of hydroxyl group at the relevant position in a native primaradiene synthase leads to an increase in reaction complexity. It is found out that substitution of a conserved Ile by Thr was sufficient to convert diverse ent-kaurene specific synthases to the specific production of ent-primara-8(14),15-diene. It is concluded that the terpene synthases played a major role in ionization.