Key structural features in cis-carane, (+)-3-carene,cis-pinane, (+)-α-pinene,and (−)-β-pinene influencing red turpentine beetle primary attraction when released with ethanol

1. In US Pacific Northwest ponderosa pine forests the primary attraction order shown previously for red turpentine beetle, Dendroctonus valens (Coleoptera: Curculionidae: Scolytinae), is (−)-β-pinene+ethanol > (+)-3-carene+ethanol > (+)-α-pinene+ethanol. The monoterpenes are bicyclic C₁₀H₁₆ isomers containing one 6-carbon ring with one double bond. Both pinenes have a 4-carbon second ring and differ only by their endocyclic or exocyclic double bond. The (+)-3-carene second ring has 3-carbons; its double bond is endocyclic like (+)-α-pinene.
2. Ring system and double bond influences on primary attraction were evaluated by hydrogenating (+)-3-carene and (+)-α-pinene to cis-carane and cis-pinane, respectively. Field test primary attraction strengths were (−)-β-pinene+ethanol > cis-carane+ethanol > cis-pinane+ethanol > ethanol.
3. In combination with ethanol (i) a double bond is not required in either ring system to attract D. valens, (ii) the cis-carane bicyclic 3, 6-carbon ring system provides stronger beetle attraction than the cis-pinane 4, 6-carbon bicyclic ring system, and likely structural basis for stronger (+)-3-carene attraction over (+)-α-pinene, (iii) adding an exocyclic double bond to the 4, 6-carbon ring system elevates attraction above the 3, 6-carbon ring system with no double bond, and (iv) the 4, 6-carbon ring system is a much stronger attractant with an exocyclic rather than endocyclic double bond.

     

Cyclic fatty esters: Stereochemistry of monounsaturated products from the hydrogenation and reduction of 9-(6-propyl-3-cyclohenxenyl)-8-nonenoic acid or its ester

Diunsaturated, C-18 cyclic fatty acid methyl esters (CFAME) were previously synthesized as model derivatives for characterization and biological evaluation of cyclic fatty acids (CFA) formed in heat-abused vegetable oils. The propyl substituted, diunsaturated CFMAE (I) was selectively reduced to prepare two monounsaturated, positional isomers with the double bond located either in the ester substituent (alkene isomer II) or in the ring (cyclohexene isomer III). The stereochemistry of these monounsaturated products was investigated by capillary GLC and NMR. Capillary GLC showed that each positional isomer was a mixture of two ‘ring’ isomers (i.e. a mixture of two isomers with side chains either cis or trans). The ring double bond in diene I was readily hydrogenated with various metal catalysts, and no cyclohexene isomer III was detected in the product. Platinum oxide poisoned with Ph₃P was the most selective catalyst examined to convert diene I to monoene II. Diimide reduction was the only method foud to reduce selectively the double bond in the ester side chain of diene I. This diimide reduction was facilitated when the Z-double bond in the side chain was isomerized to E-double bond with p-toluenesulfinic acid. Cyclohexene isomer III and alkene isomer II were separated by argentation HPLC. These two isomeric monoenes were characterized by GC-MS, capillary GLC, micro-ozonolysis, IR and NMR. Catalytic hydrogenation with Ph₃P-poisoned PtO₂ and diimide reduction of the diunsaturated cyclic ester may provide useful methods to synthesize and label monounsaturated cyclic fatty esters.     

UV-spectroscopy,electronic structure and ozonolytic reactivity of sesquiterpenes: a theoretical study

Sesquiterpenes, one of the most important classes of biogenic volatile organic compounds, are potentially significant precursors to secondary organic aerosols (SOAs) in nature. The electronic structure of sesquiterpenes and their reactivity in the ozonolysis reaction were investigated by density functional theory. Results from the CIS calculations combined with an analysis of transition intensities show that the first peaks in the ultraviolet (UV) spectra for saturated and unsaturated isomers are σ–σ* and π–π* transitions, respectively. The UV absorption wavelength and absorbency are dictated by the electronic structures of these compounds. An increase in the number of double bonds and formation of a conjugated system expand the range of absorption in the UV region. An isomer with an endocyclic C = C bond presents weaker UV transition intensity than its corresponding exocyclic isomer. Results from conceptual DFT chemical reactivity indices of isomers suggest that no quantitative linear relationships between the structural changes and their reactivity, such as different degrees of unsaturated C = C double bonds, or the number of substituents attached to the C = C bond were discovered. In the ozonolysis reaction of sesquiterpenes, isomers with larger steric hindrance of substituents or endocyclic C = C bond possess higher chemical reactivity compared to isomers with smaller steric hindrandce or with an exocyclic C = C bond. These results are imperative to a better understanding of SOAs production mechanisms in the troposphere.     

Enantiomeric Neolignans and a Sesquiterpene from Solanum erianthum and Their Absolute Configuration Assignment

One pair of new C‐8–C‐3′/C‐7–O–C‐4′ linked neolignan enantiomers ( 1a / 1b ) and one new guaiane sesquiterpene ( 2 ) first featuring the 1(2),9(10)‐conjugated double bond were isolated from the stems of Solanum erianthum (Solanceae). Their structures were characterized on the basis of extensive spectroscopic analyses, especially from their 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations of 1a / 1b were rigorously elucidated by electronic circular dichroism (ECD) experiments combined with the reversed helicity rule for the 2,3‐dihydrobenzo[b]furan chromophore, and compound 2 is the first report on the sterochemical assignment of a guaiane sesquiterpene by using the allylic axial chirality rule for the conjugated diene chromophore in combination with the calculated ECD spectrum. Chirality 28:259–263, 2016. © 2016 Wiley Periodicals, Inc.     

Formation of adducts of parthenin and related sesquiterpene lactones with cysteine and glutathione.

Parthenin, the major sesquiterpene lactone of Parthenium hysterophorus, a weed responsible for dermatitis in man is primarily restricted to leaf and stem trichomes. Parthenin forms a monoadduct with L-cysteine through the alpha-methylene group of the gamma-lactone and a biadduct with the endocyclic double bond on the cyclopentenone ring. Studies with other sesquiterpene lactones support the view that the types of adducts formed are correlated with the biological activity of the sesquiterpene lactones.     

Alcoxyhalogenation d'acides gras ethyleniques. IV: Cas des octadécadienoates de méthyle 9c, 12c et 9t, 11t et de composés apparentés

Methoxybromination, with HBBT, of long chain methylene interrupted dienes led to simultaneous formation of methoxybromides and dimethoxydibromides. Formation of dimethoxydibromides in which methoxy groups are both internal is limited by steric hindrance.Methoxybromination of long chain conjugated dienes forms, in nearly equal quantities, methoxybromides resulting from a 1,4 addition and methoxybromides from 1,2 addition in which the methoxy group is adjacent to the double bond.     

Control of female pheromones in Drosophila melanogaster by homeotic genes

We have investigated the role of the Antennapedia and Bithorax complexes (ANT-C and BX-C) on the production of cuticular hydrocarbons in Drosophila melanogaster. In males, there is little, if any, influence of these complexes on the hydrocarbon pattern. In females, there are large and opposite effects of these complexes on diene production: two ANT-C mutations cause an increase in diene production and a reduction of monoenes, whereas most BX-C mutations result in a decrease in dienes and an increase in monoenes, although their sum remains constant. The effect is the highest in Mcp and iab6 females. It is suggested that a factor originating from the prothorax might activate the conversion of monoenes to dienes in females. The abdomen seems to have a crucial role in the production or control of pheromones: abdominal segments four to seven have the main effects, with a most dramatic effect for segments four and five.     

Halogenated 2,5-pyrrolidinediones: synthesis, bacterial mutagenicity in Ames tester strain TA-100 and semi-empirical molecular orbital calculations

The chloroimide 3,3-dichloro-4-(dichloromethylene)-2,5-pyrrolidinedione, a tetrachloroitaconimide, is the principal mutagen produced by chlorination of simulated poultry chiller water. It is the second most potent mutagenic disinfection by-product of chlorination ever reported. Six of seven new synthetic analogs of this compound are direct-acting mutagens in Ames tester strain TA-100. Computed energies of the lowest unoccupied molecular orbital (E(LUMO)) and of the radical anion stability (DeltaH(f)(rad)-DeltaH(f)) from MNDO-PM3 for the chloroimides show a quantitative correlation with the Ames TA-100 bacterial mutagenicity values. The molar mutagenicities of these direct acting mutagenic imides having an exocyclic double bond fit the same linear correlation (lnM(m) vs. E(LUMO); lnM(m) vs. DeltaH(f)(rad)--DeltaH(f)) as the chlorinated 2(5H)-furanones, including the potent mutagen MX, 3-chloro-4-(dichloro-methyl)-5-hydroxy-2(5H)-furanone, a by-product of water chlorination and paper bleaching with chlorine. Mutagenicity data for related haloimides having endocyclic double bonds are also given. For the same number of chlorine atoms, the imides with endocyclic double bonds have significantly higher Ames mutagenicity compared to their structural analogs with exocyclic double bonds, but do not follow the same E(LUMO) or DeltaH(f)(rad)-DeltaH(f) correlation as the exocyclic chloroimides and the chlorinated 2(5H)-furanones.     

Selective hydroboration of dieneamines. Formation of hydroxyalkylphenothiazines as MDR modulators

N-dienylphenothiazines synthesized from tetrazolo[1,5-a]pyridinium salts by treatment with phenothiazine were subjected to catalytic hydrogenation to yield N-butylphenothiazines, whereas transformation of these dienes with borane dimethyl sulfide (BH(3) × Me(2)S) resulted in selective hydroboration of one double bond and full reduction of the other double bond to give 2-hydroxybutylphenothiazines. Position of the hydroxyl group was supported by NMR spectroscopy and verified by X-ray analysis. Comparison of MDR modulatory activity of the new derivatives revealed that the hydroxybutyl compounds are promising candidates for development of novel MDR inhibitors.     

Biosynthesis of carvone in Mentha spicata

Degradation of, and measurement of isotope ratios in, (?)-carvone that had been biosynthesized in Mentha spicata from ³H- and ¹⁴C-labelled geraniol and mevalonate indicate that (a) oxidation of limonene or its biogenetic equivalent to form carvone involves shift of the endocyclic double bond; (b) (+)-limonene and (?)-carvone are biogenetically related and are probably formed on divergent pathways from a common intermediate; and (c) the exocyclic double bond of carvone is not formed regiospecifically. These results enable the mechanisms for the introduction of the carbonyl group and for the formation of the isopropenyl side-chain to be delimited.     

Metabolism of monoterpenes: demonstration that (+)-cis-isopulegone, not piperitenone, is the key intermediate in the conversion of (-)-isopiperitenone to (+)-pulegone in peppermint (Mentha piperita)

Piperitenone is commonly considered to be the key intermediate in the conversion of (-)-isopiperitenone to (+)-pulegone in peppermint; however, [3H]piperitenone gave rise only to the inert metabolite (+)-piperitone when incubated with peppermint leaf discs. Under identical conditions, (-)-[3H]isopiperitenone was efficiently incorporated into (+)-pulegone, (-)-menthone, and (+)-isomenthone in leaf discs, and yielded an additional metabolite identified as (+)-cis-isopulegone; piperitenone was poorly labeled. Moreover, (+)-cis-[3H]isopulegone was rapidly converted to (+)-pulegone, (-)-menthone, and (+)-isomenthone in leaf discs, and the reduction of (+)-[3H]pulegone to (-)-menthone and (+)-isomenthone was similarly documented. Each step of the pathway was demonstrated in a crude soluble preparation from peppermint leaf epidermis and each of the relevant enzymes was partially purified in order to compare relative rates of catalysis. The results of these studies indicate that the endocyclic double bond of (-)-isopiperitenone is reduced to yield (+)-cis-isopulegone, which is isomerized to (+)-pulegone as the immediate precursor of (-)-menthone and (+)-isomenthone, and they rule out piperitenone as an intermediate of the pathway.     

Lipid peroxidation and nutrition

Levels of conjugated dienes of fatty acids (first peroxidation product) in relation to their substrates and promotors (triacylglycerols, homocysteine, iron) as well as to their inhibitors (essential antioxidative vitamins) were assessed in a vegetarian group (n=24) and compared with subjects on a mixed diet (traditional nutrition, n=24). Positive significant linear correlation between conjugated dienes and triacylglycerols, homocysteine, iron as well as inverse relationship between conjugated dienes and vitamin E, vitamin C, beta-carotene were observed in pooled groups. Lipid peroxidation risk in vegetarians seems to be caused predominantly by hyperhomocysteinemia, whereas in a mixed diet group this was due to a higher supply of substrates or risk iron values. The incidence of only 8 % of risk conjugated diene values in vegetarians in contrast to 42 % in the group with traditional diet indicates that vegetarians have a better antioxidative status as a consequence of regular consumption of protective food.     

Chiroptical properties of binuclear rhodium complexes of lanostane alcohols

The circular dichroism (CD) of the in situ-formed Rh2(OCOCF3)4 complexes of sterically hindered, secondary lanostane alcohols was investigated. The main object of the present studies are derivatives of 3beta-, 7alpha-, 7beta-, and 11beta-hydroxylanostanes with or without an additional functional group, e.g., double bond, oxo-, hydroxy-, or acetoxy groups. Up to five Cotton effects (CEs) can be found in the CD spectra of Rh-complexes of these alcohols in the spectral range between 650-300 nm. Correlation of the CEs signs with the absolute stereochemistry at the carbon atom bearing the hydroxy group was investigated. The Rh-complex with the 3beta-acetoxylanostan-11beta-ol ligand was isolated in the crystalline form. Its polymeric structure, determined by the X-ray method, shows the di-Rh-units linked by the axially ligating oxygen atoms of the hydroxy and acetoxy groups. In the latter case, the coordination takes place through the carbonyl oxygen.     

Phenylalanine ammonia-lyase: enzymic conversion of 3-(1,4-cyclohexadienyl)-L-alanine to trans-3-(1,4-cyclohexadienyl)acrylic acid.

The phenylalanine analogue 3-(1,4-cyclohexadienyl)-L-alanine is converted to the hitherto unknown cinnamate analogue trans-3-(1,4-cyclohexadienyl)acrylic acid by L-phenylalanine ammonia-lyase (EC 4.3.1.5) from maize, potato, or Rhodotorula glutinis. The structure assigned to the product is confirmed by its 1H nuclear magnetic resonance spectrum and by the chemical synthesis to be described in a subsequent paper. On comparing the above substrate analogue with L-phenylalanine, the Km was lowered only slightly but kcat was reduced 14--40-fold depending on the source of the enzyme. Because the compounds closely resemble each other in size and hydrophobic properties, this lowering of kcat may be attributed to the electronic effect of replacing the pi electrons of the aromatic system by those of a double bond. Correct alignment at the active site appears to depend upon the space-filling properties of the ring system; open chain analogues that retain the gamma, beta double bond were found to be inhibitors, not substrates.     

Olefin isomerization regiochemistries during tandem action of BacA and BacB on prephenate in bacilysin biosynthesis

BacA and BacB, the first two enzymes of the bacilysin pathway, convert prephenate to an exocylic regioisomer of dihydrohydroxyphenylpyruvate (ex-H(2)HPP) on the way to the epoxycyclohexanone warhead in the dipeptide antibiotic, bacilysin. BacA decarboxylates prephenate without aromatization, converting the 1,4-diene in prephenate to the endocyclic 1,3-diene in Δ(4),Δ(8)-dihydrohydroxyphenylpyruvate (en-H(2)HPP). BacB then performs an allylic isomerization to bring the diene into conjugation with the 2-ketone in the product Δ(3),Δ(5)-dihydrohydroxyphenylpyruvate (ex-H(2)HPP). To prove that BacA acts regiospecifically on one of the two prochiral olefins in prephenate, we generated 1,5,8-[(13)C]-chorismate from bacterial fermentation of 5-[(13)C]-glucose and in turn produced 2,4,6-[(13)C]-prephenate via chorismate mutase. Tandem action of BacA and BacB gave 2,4,8-[(13)C]-7R-ex-H(2)HPP, showing that BacA isomerizes only the pro-R double bond in prephenate. Nonenzymatic isomerization of the BacA product into conjugation gives only the Δ(3)E-geometric isomer of Δ(3),Δ(5)-ex-H(2)HPP. On the other hand, acceleration of the allylic isomerization by BacB gives a mixture of the E- and Z-geometric isomers of the 7R- product, indicating some rerouting of the flux, likely through dienolate geometric isomers.     

Biological origins of normal-chain hydrocarbons: a pathway model based on cuticular wax analyses of maize silks

Long-chain normal hydrocarbons (e.g. alkanes, alkenes and dienes) are rare biological molecules and their biosynthetic origins are obscure. Detailed analyses of the surface lipids that accumulate on maize silks have revealed that these hydrocarbons constitute a large portion (>90%) of the cuticular waxes that coat this organ, which contrasts with the situation on maize seedling leaves, where the cuticular waxes are primary alcohols and aldehydes. The normal hydrocarbons that occur on silks are part of a homologous series of alkanes, alkenes and dienes of odd-number carbon atoms, ranging between 19 and 33 in number. The alkenes and dienes consist of a homologous series, each of which has double bonds situated at defined positions of the alkyl chains: alkenes have double bonds situated at the sixth, ninth or 12th positions, and dienes have double bonds situated at the sixth and ninth, or ninth and twelfth positions. Finding a homologous series of unsaturated aldehydes and fatty acids suggests that these alkenes and dienes are biosynthesized by a series of parallel pathways of fatty-acid elongation and desaturation reactions, which are followed by sequential reduction and decarbonylation. In addition, the silk cuticular waxes contain metabolically related unsaturated long-chain methylketones, which probably arise via a decarboxylation mechanism. Finally, metabolite profiling analyses of the cuticular waxes of two maize inbred lines (B73 and Mo17), and their genetic hybrids, have provided insights into the genetic control network of these biosynthetic pathways, and that the genetic regulation of these pathways display best-parent heterotic effects.     

Lipid peroxidation and molecular damage to polyunsaturated fatty acids in rat liver. Recognition of two classes of hydroperoxides formed under conditions in vivo

The diene conjugates formed during the autoxidation of microsomal lipid extracts, and in endoplasmic reticulum in vivo after exposing rats to CCl4 have been examined by second derivative absorption spectrophotometry. Within a few minutes after administering CCl4 to a rat there is a pronounced signal in microsomal lipid extracts that is ascribed to the cis-trans diene conjugates of microsomal polyunsaturated fatty acids. Somewhat later a second signal becomes evident that is ascribed to trans-trans isomers. The appearance of the trans-trans isomer is very strongly suppressed by prior administration of vitamin E to the rat. It is concluded that the relative contents of cis-trans and trans-trans dienes in lipid extracts of tissue reflect the tissue contents of hydrogen donors as already established for model experiments with polyunsaturated fatty acids in vitro.     

Molecular mechanics (MM3(pi)) conformational analysis of molecules containing conjugated pi-electron fragments: Leucomycin-V

The conformations of the 16-membered macrolide antibiotic leucomycin-V (1) were studied with molecular mechanics. Leucomycin-V contains a conjugated pi-electron fragment and necessitates special treatment with the MM3(pi) modeling protocol. Comparison was made with results from the standard MM3 scheme. The CONFLEX conformational search procedure was used for finding low-energy conformations. The computed data are indicative for the existence of mainly one conformation of the macro-ring of 1 and minor participation of several others. Intramolecular hydrogen bonds play important roles for the preferred geometry of the macro-ring and the conformations of the side chains. The most probable macro-ring conformation of 1 is very similar to the preferred conformation of another 16-ring macrolide antibiotic, tylosin. The same order of conformational preference for 1 was estimated with the MM3 and the MM3(pi) methods. Surprisingly, when changing the chirality of the C(9) macro-ring atom of 1, the two methods produced different order of conformational preferences for the 9-epi form (2), as well as enhanced population of several clusters of conformations.     

Relationships between lipid peroxidation and anoxia tolerance in a range of species during post-anoxic reaeration

Peroxidation was studied in anoxically treated plant tissues and quantified as conjugated dienes/trienes in the total lipid fraction and as the production of thiobarbituric acid reactive substances (TBARS). Oxidative stress caused by re-exposure of plants to oxygen led to an increase of conjugated diene/triene formation in rhizomes of Iris germanica and roots of wheat ( Triticum aestivum L.) and oats ( Avena sativa L.), and after a long anoxic exposure (45 days) in the rhizomes of the very anoxia tolerant Iris pseudacorus . Second derivative (SD) spectrophotometry of the UV spectrum of lipid extracts confirmed the formation of dienes. However, determination of TBARS in Iris spp. showed no lipid peroxidation in the anoxia tolerant I. pseudacorus . In the rhizomes of the anoxia intolerant I. germanica , elevated levels of TBARS correlated positively with conjugated diene/triene formation. The results suggest that anoxic stress may induce qualitative changes in membrane lipids, as indicated by lipid peroxidation after restoration of aerobic conditions. The rate of lipid peroxidation correlated negatively with anoxic stress tolerance.     

Continuous Monitoring of in Vztro Oxidation of Human Low Density Lipoprotein

The kinetics of the oxidation of human low densit) lipoprotein (LDL) can be measured continuously by monitoring the change of the 234 nm diene absorption. The time-course shows three consecutive phases, a lag-phase during which the diene absorption increases only weakly. a propagation phase with a rapid increase of the diene absorption and finally a decomposition phase. The increase of the dienes is highly correlated with the increase of MDA or lipid hydroperoxides. The duration of the lag-phase is determined by the endogenous antioxidants contained in LDL (vitamin E. carotenoids. retinylstearate). Water-soluble antioxidants (ascorbic acid. urate) added in micromolar concentrations prolong the lag-phase in a concentration-dependent manner. The determination of the lag-phase is a convenient and objective procedure for determining the susceptibility of LDL from different donors towards oxidation as well as effects of pro-and antioxidants.