Search

Walrobsins A (1) and B (2), two limonoids featuring an unprecedented 5-oxatricyclo[5.4.11,4]hendecane ring system, were isolated from the root barks of Walsura robusta. Their structures, including their absolute configurations, were determined by analyses of HR-ESIMS, 1D/2D NMR, and X-ray crystallography. Compounds 1 and 2 possessed a stable hemiketal structure formed between the OH-11 and 3-carbonyl group in the hexatomic oxoheterocyclic ring. Compound 1 showed significant anti-inflammatory activity with an IC50 value of 7.8 μM and inhibited the expression of iNOS and IL-1β in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

A systematic study of the biomimetic pathways to yezo'otogirin C under aerobic and anaerobic conditions has been investigated, and both are found to be feasible pathways to the natural product depending on the physiological conditions. Because of the lower activation energy, the aerobic process would be more favorable when the in vivo oxygen level is high. In the course of this study, a highly efficient synthetic route to (±)-yezo'otogirin C has been established in four steps (31% overall yield) from a readily available compound without using any protecting groups. The natural product and its structural analogues exhibited antitumor activities against several human cancer cell lines and appeared to arrest cell cycles in different phases. [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]

Anditomin and its precursors, andilesins, are fungal meroterpenoids isolated from Aspergillus variecolor and have unique, highly oxygenated chemical structures with a complex bridged-ring system. Previous isotope-feeding studies revealed their origins as 3,5-dimethylorsellinic acid and farnesyl pyrophosphate and suggested the possible involvement of a Diels-Alder reaction to afford the congested bicyclo[2.2.2]octane core structure of andilesins. Here we report the first identification of the biosynthetic gene cluster of anditomin and the determination of the complete biosynthetic pathway by characterizing the functions of 12 dedicated enzymes. The anditomin pathway actually does not employ a Diels- Alder reaction, but involves the nonheme iron-dependent dioxygenase AndA to synthesize the bridged-ring by an unprecedented skeletal reconstruction. Another dioxygenase, AndF, is also responsible for the structural complexification, generating the end product anditomin by an oxidative rearrangement. [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]

The thermal rearrangement of α-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states. [ABSTRACT FROM AUTHOR]

The term "housane" refers to molecules possessing a bicyclo[2.1.0]pentane core. One was designed, synthesized, and used as a precursor of daucene, a member of the carotane class of sesquiterpenes. The total synthesis was completed, thereby marking the first time that housane-derived cation radicals have been used as the key intermediate in the synthesis of a natural product. The transformation used in the construction and featured in the text involves an oxidation to generate the cation radical via either a chemically or an electrochemically mediated electron transfer, the latter process using tris(p-bromophenyl)amine as the mediator. The two methods are compared, and guiding principles are formulated to assist in deciding how best to implement each. Both processes afford an unfavorable equilibrium state that is subsequently drained toward the product by two irreversible events, viz., a 1,2 carbon migration to the site that best stabilizes a positive charge and a second electron transfer, this time being a highly exothermic reduction of the rearranged species to generate the neutral product. A mechanistic proposal calling for the use of a catalytic quantity of the electrochemical mediator and the consumption of exceptionally small quantities of current is advanced. Experimental deviations from these predictions are noted, and a rationale to account for them is presented. Finally, significant differences were noted between the cyclic voltammograms of housanes bearing a CH2OR substituent rather than a methyl group at the bridgehead carbon. Those having the inductively withdrawing group displayed broad and ill-defined curves. The differences were investigated quantum mechanically, and a stereoelectronic argument is formulated stating that broadness of the curve for the ROCH2-substituted systems is the result of a time-averaged sampling of the HOMO energies over the distribution of conformers. The possible generality of the stereoelectronic effect is noted. [ABSTRACT FROM AUTHOR]

Cipadonoid A ( 1), a novel limonoid with an unprecedented skeleton, was isolated from the leaves of Cipadessa cinerasecns. Its structure and relative configuration were determined by spectroscopic analysis and computer modeling. 1represents a new type of limonoid, characterized by a rearranged tetrahydropyranyl ring B incorporating usually exocyclic C-30. A possible biosynthetic pathway of 1was also proposed. [ABSTRACT FROM AUTHOR]

The sesquiterpene nanaimoal was synthesized in 21% overall yield and in a biomimetic manner. As a key step, the acid- catalyzed cyclization of farnesal under zeolite NaY confine- ment conditions was used. The intrazeolite cyclization of farnesal affords as major product a double-bond isomer of nanaimoal, via a novel diastereoselective tandem I ,5-diene cyclization/Prins-type reaction. [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]

The glycoterpenoid syphonoside (1) is the main secondary metabolite of both the marine mollusk Syphonota geographica and the sea-grass Halophila stipulacea, two Indo-Pacific species migrated to the Mediterranean Sea through the Suez Canal. The structure and the absolute stereochemistry of 1, which displays unique structural features, has been accomplished by using a combination of spectroscopic techniques, degradation reactions, and conformational analysis methods. Compound 1 was able to inhibit high density induced apoptosis in a number of human and murine carcinoma cell lines. [ABSTRACT FROM AUTHOR]

Synthesis of (23E)-cycloart-23-ene-3β,25-diol (1) and its 23Z-isomer 2 was achieved by using cycloartenol as a starting material, thus revising the proposed structure of natural 2 to 1 unequivocally. These synthetic studies revealed that the structural revision (Z-form → E-form) should also be applied to terpenoids such as (23Z)-3β-acetoxyeupha-7,23-diene-25-ol, (23Z)-tirucalla-7,23-diene-3β,25-diol, quadrangularol A, quadrangularic acid K, and daurichromene C. [ABSTRACT FROM AUTHOR]

An organic tracer method, recently proposed for estimating individual contributions of toluene and α-pinene to secondary organic aerosol (SOA) formation, was evaluated by conducting a laboratory study where a binary hydrocarbon mixture, containing the anthropogenic aromatic hydrocarbon,toluene, and the biogenic monoterpene, α-pinene, was irradiated in air in the presence of NOx to form SOA. The contributions of toluene and α-pinene to the total SOA concentration, calculated using the organic tracer method, were compared with those obtained with a more direct 14C content method. In the study, SOA to SOC ratios of 2.07 ± 0.08 and 1.41 ± 0.04 were measured for toluene and α-pinene SOA, respectively. The individual tracer-based SOA contributions of 156 µg m-3 for toluene and 198 µg m-3 for α-pinene, which together accounted for 82% of the gravimetrically determined total SOA concentration, compared well with the 14C values of 182 and 230 µg m-3 measured for the respective SOA precursors. While there are uncertainties associated with the organic tracer method, largely due to the chemical complexity of SOA forming chemical mechanisms, the results of this study suggest the organic tracer method may serve as a useful tool for determining whether a precursor hydrocarbon is a major SOA contributor. [ABSTRACT FROM AUTHOR]

The nonmevalonate isoprenoid pathway is an established target for antiinfective drug development. This paper describes high-throughput methods for the screening of 2C-methyl-n-erythritol synthase (IspC protein), 4-diphosphocytidyl-2C-methyl-D-erythritol synthase (IspD protein), 4-diphosphocytidyl-2C-methyl-D-erythritol kinase (IspE protein), and 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF protein) against large compound libraries. The assays use up to three auxiliary enzymes. They are all monitored photometrically at 340 nm and are robust as documented by Z-factors of ≥0.86. 13C NMR assays designed for hit verification via direct detection of the primary reaction product are also described. Enzyme-assisted methods for the preparation, on a multigram scale, of isoprenoid biosynthesis intermediates required as substrates for these assays are reported. Notably, these methods enable the introduction of single or multiple 13C labels as required for NMR-monitored assays. The preparation of 4-diphosphos-phocytidyl-2C-methyl-D-erythritol 2-phosphate in multigram quantities is described for the first time. [ABSTRACT FROM AUTHOR]

The article provides insights in structural biology and chemistry of the terpenoid cyclases. Terpenoid cyclases catalyze the most complex chemical reactions occuring in the environment. They generate a unique hydrocarbon product with remarkable structural and stereochemical precision. The article also discusses monototerpene cyclases, diterpene cyclases, triterpene cyclases and antibody catalysis of cationic cyclization reactions.

A laboratory study was carried out to investigate the secondary organic carbon (SOC) yields of α-pinene and isoprene in the presence of SO2, which produces acidic aerosol in the system. Experiments were based on irradiating each hydrocarbon (HC) with NOx in a 14.5 m³ smog chamber operated in the dynamic mode. The experimental design consisted of several multi-part experiments for each HC. In the first part of each experiment, an HC/NOx irradiation was conducted in the absence of SO2 and was followed by irradiations with the addition of SO2 in subsequent parts. Filter-based analyses for organic carbon were made using a thermal-optical approach either with an off-line instrument or in situ with an automated instrument. For isoprene in the absence of SO2, the SOC yield was approximately 0.001, a value consistent with earlier work from this laboratory. With the addition of up to 200 ppb SO2, the yield increased by a factor of 7. For α-pinene in the absence of SO2, the SOC yield of the irradiated mixture was found to average 0.096 from two experiments. With SO2 in the system, the SOC yield increased on average to 0.132. These results suggest that SO2, and by inference acidic aerosol, may play a role in increasing the yield of SOC from the photooxidation products of biogenic hydrocarbons or by the direct uptake of biogenic hydrocarbons onto acidic aerosol. [ABSTRACT FROM AUTHOR]

Atmospheric standards containing parts-per-billion levels of 14 semivolatile hydrocarbon compounds, including eight sesquiterpenes (SQTs) (longipinene, α-copaene, isolongifolene, α-cedrene, trans-caryophyllene, aromadendrene, α-humulene,δ-cadinene), two oxidized sesquiterpenoids (cis-nerolidol, trans-nerolidol), one biogenic ketone (geranyl-acetone) and three aromatic compounds (1,3,5-tri-isopropylbenzene, diphenylmethane, nonylbenzene), were collected onto four solid adsorbent materials at increasing ozone mixing ratios (0-100 ppbv O3) for analysis by thermodesorption-gas chromatography. Substantial sampling losses of up to >90% were found for the most reactive SQT, even at the lowest ozone level investigated of 20 ppbv. Loss rates from the ozone–SQT reaction were used to derive estimates of gas-phase ozone reaction rate constants for longipinene, α-copaene, isolongifolene, geranylacetone, aromadendrene, δ-cadinene, cis-nerolidol, and trans-nerolidol. Three different ozone mitigation techniques were investigated to prevent these sampling losses. These strategies included (a) placing glass fiber filters impregnated with sodium thiosulfate (Na2S2O3) into the sampling line, (b) titration of ozone in the sampling stream with nitric oxide (NO), and (c) catalytically removing ozone with a commercially available manganese dioxide (MnO2) catalyst. All three techniques reduced ozone-mixing ratios from 100 ppbv to <0.6 ppbv at sampling flow rates of 1 L min-1. When the Na2S2O3 fitters and the NO-titration techniques were applied, SQT loss rates decreased from 25-60% to 0-5% for most SQT compounds and from >90% to ∼-10-50% for the two most reactive compounds at ozone mixing ratios of up to 100 ppbv. The commercial manganese dioxide scrubber, however, caused complete analyte losses (>98%) even at 0 ppbv ozone. These results underline the need and present applicable techniques for removal of ozone in air samples for SQT analysis by solid adsorption techniques. [ABSTRACT FROM AUTHOR]

In nature there are several terpenoids with a characteristic γ-dioxygenated system on the A ring, and many of them show interesting pharmacological properties. We have developed a novel strategy for the synthesis of these terpenoids involving three stages: (a) the selective epoxidation of commercial polyenes, (b) titanium(III)-catalyzed cyclization of the epoxypolyprenes thus obtained, and (c) Pd-mediated remote functionalization of the equatorial methyl group attached at C-4 on ring A of the cyclic terpenoid thus formed. This strategy has proved to be useful for the synthesis of the natural labdane rostratone (1) and related terpenoids, as well as for advanced synthetic approaches toward the pharmacologically active products aphidicolin (2) and pyripyropene A (3). [ABSTRACT FROM AUTHOR]

A liquid chromatography/sonic spray ionization mass spectrometry method (LC/SSI-MS) was developed for qualitative and quantitative analyses of ginkgo terpene trilactones. Five ginkgo terpene trilactones were successfully protonated for qualitative and quantitative analyses under the study conditions. The typical ion adducts were identified as (M + H)+, (M + NH4)+, and (M + Na)+. The limits of detection were achieved between 2.5 and 10 ng with RSD of 0.173-4.82% and a linear range of 10-80 ng with R² = 0.991-0.999. This method was used to identify and quantify ginkgo terpene trilactones in extractions of ginkgo biloba leaves obtained from three different extraction methods. This is the first completely validated LC/MS method for quantification of ginkgo terpene trilactones. The factors that contributed to reduce the errors of identification and quantification of ginkgo terpene frilactones are systematically reported, and the advantages and disadvantages of LC/MS method in quantitative analysis are also discussed. [ABSTRACT FROM AUTHOR]

A new and efficient synthesis of a variety of highly embellished bicyclooctenones having an endo- vinyl moiety and their sigmatropic shifts in ground and excited states leading to a stereoselective route to substituted cis-decalins and diquinane frameworks have been described. Functionalized bicyclo[2.2.2]octenones having an endo-vinyl group and a β,γ-enone chromophore were prepared by in situ generation of 6-chloromethyl-6-hydroxycyclohexadienones and cycloaddition with butadiene (also generated in situ) followed by manipulation of the adducts. The presence of contiguous carbonyl, hydroxyl, and chloromethyl groups in adducts led to the introduction of various alkyl groups α to the ketone in a stereoselective fashion. The 3,3-sigmatropic shift in the bridged bicyclic compounds gave the corresponding cis-decalins, whereas the triplet sensitized irradiation led to the formation of diquinanes as a result of a 1,2-acyl shift. [ABSTRACT FROM AUTHOR]

The construction of strained carbon skeletons by ring-closing olefin metathesis (RCM) was investigated. With well-designed diene 4, RCM was found to be applicable to the formation of a highly strained inside-outside bicyclo(4.4.1)undecane skeleton of ingenol, a bioactive diterpenoid, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of the ketone with an allylic chloride unit, 26, and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 6, the key intermediate aldehyde 9 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol. [ABSTRACT FROM AUTHOR]

A method was developed for the extraction and quantification of pharmacologically active terpene trilactones (ginkgolides, bilobalide) from the tissues of Ginkgo biloba L. and pharmaceutical ginkgo products by RP- HPLC, based on the theory of terpene trilactones ionization. Four ginkgolides (GA, GB, GC, GJ) and biobalide (BB) from both the ginkgo leaves and commercially available ginkgo extracts were quantitatively extracted by using this method. The recovery rate of the method was 97.5- 100% with RSD of 1.2-2.8%. The detection limit was 0.05-0.1 μg, and the linear range was 0.1-12 μg. This detection limit represents a marked improvement over previously reported methods, suggesting the new method is a viable technique for routine analysis of ginkgo terpene trilactones in natural and commercial samples. The method reported by van Beek et al. in 1991 (van Beek, T.A.; Scheeren, H. A.; Rantio T.; Melger, W. C.; Lelyveld, G. P. J. Chromatogr. 1991,543,375-387.) was used as a reference method to monitor the accuracy of extraction and analysis in this study. SSI-MS technique was used to identify isolated target components. Carbohydrase treatment and solubility of terpene trilactones in various solvents were also discussed. [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]

Carotenoids play an important role of light harvesting, photoprotection and structural stabilization in the photosynthetic organisms. Despite their functional importance, the molecular basis for binding of carotenoids in the photosynthetic pigment−protein complexes is poorly understood. On the basis of a recent discovery that carotenoids are surrounded either by aromatic residues or by chlorophylls in all known crystal structures of the photosynthetic pigment−protein complexes (J. Am. Chem. Soc. 2002, 124, 8445), it is hypothesized that &pgr;−&pgr; stacking interactions are the molecular forces that bind carotenoids in the photosynthetic pigment−protein complexes. In this article, the &pgr;−&pgr; stacking interactions between the carotenoid molecule peridinins and their surrounding aromatic groups (aromatic residues and chlorophyll-a) in the peridine−chlorophyll−protein complex of Amphidinium carterae are characterized by means of the supermolecular approach with the second-order Møller−Plesset perturbation method (MP2). The modified 6-31G*(0.25) basis set with diffuse d-polarization by Hobza et al. is adopted here. A representative peridinin chlorophyll pair (PID624···Chl602) is chosen to study the structural stabilization role of peridinin, and three unique peridinin and aromatic residue pairs (PID623···TYR270, PID624···PHE301, and PID624···PHE304) are chosen to study the configurational (orientation and distance) dependence of &pgr;−&pgr; stacking interactions between peridinins and their interacting partners. The MP2/6-31G*(0.25) calculations yielded a favorable &pgr;−&pgr; stacking interaction energy of −11.52 kcal/mol between the large conjugated tetrapyrrol &pgr;-system of chlorophyll Chl602 and the long conjugated &pgr;-electrons of peridinin PID624. For the parallelly oriented PID623···TYR270 pair, the MP2/6-31G*(0.25) calculations give rise to a stabilization energy of −7.25 kcal/mol. For the perpendicularly oriented pairs, the calculated MP2/6-31G*(0.25) &pgr;−&pgr; stacking energies are −3.77 and −1.71 kcal/mol for PID624···F301 and PID624···F304, respectively. It is thus concluded that &pgr;−&pgr; stacking interactions between peridinins and the nearby aromatic groups play a substantial role in binding peridinins in the peridine−chlorophyll−protein complex of A. carterae. Consequently, the molecular basis of the structural stabilization function of carotenoids in forming the pigment−protein complexes is unraveled. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the ozonolytic decomposition of terpenoids and terpenes, during sampling on Tenax, in an artificial air system at ambient concentration levels. Dependence of detrimental effect of 8-150 ppbv on chemical structure of compounds; Enhancement of analytical recoveries for many compounds when sampling duration is reduced from 10 minutes to 30 seconds.

(±)-Paeonilide, a novel monoterpenoid metabolite from the roots of Paeonia delavayi showing anti-platelet activating factor activity, is convergently synthesized in five steps with 59% overall yield. The application of benzoyl peroxide-promoted radical addition of unsaturated ester to aldehyde and subsequent topologically favored cyclization greatly simplified the synthesis. [ABSTRACT FROM AUTHOR]

The article reports on the potential of cycloalkane skeleta of terpenoids for the potential of combining polyepoxide cyclizations with biomimetric polyene cyclizations. The viabilities of the cyclization processes for durgamone and nakorone are tested via diepoxide cyclizations terminated by carbon nucleophiles.