This thesis describes the synthetic preparation of somecompounds, which can serve as chemical signals for use in thedevelopment of control methods for pest insects. The compoundssynthesised are of the isoprenoid type and of two kinds:carvone derivatives and germacranes. The derivatives of carvoneare based on modifications of this compound, by reactions ofeither its endocyclic or its exocyclic double bond. One type ofmodifications was accomplished by chemoselective additions ofthiophenol. The latter ones imply additions to the exocyclicdouble bond and seem to constitute general, previously rarelystudied reactions. In other modifications of its exocyclic side chain, carvoneafforded some sesqui- and diterpeniod natural products. Thefollowing compounds were synthesised in an enantioselectiveway: (-)-epi-delobanone, (-)-delobanone,(-)-7-hydroxy-3,10-prenylbisaboladien- 2-one (an insecticidalconstituent of Croton linearis) as well as its diastereomer andsome other compounds with similar structures. All of thesecompounds weretested for their antifeedant/feeding deterrentcapability against gnawing of the pine weevil, Hylobiusabietis. The germacranes prepared by means of enantioselective totalsyntheses are: (–)- 1(10),5-germacradien-4-ol and(–)-germacrene D. The former is a constituent of thedefence secretion (an allomone) from the larvae of the pinesawfly, and the needles of Scots pine. (–)-Germacrene D isa ubiquitous compound in nature. For example, it occurs in thepeels of apples and acts as one component of a lure (akairomone) to the apples, which attracts the codling moth,Cydia pomonella. The main problem in the total syntheses of the germacraneswas the formation of the unsaturated monocyclic 10-memberedring. This was achieved by intramolecular alkylation with asuitably functionalised/protected cyanohydrin derivative,which, after further elaboration, afforded a monocyclic10-membered enone, that was used in the syntheses of the twogermacranes mentioned above. In the initial steps in thesynthetic sequence the stereochemistry was established byalkylation of an amide enolate attached to a chiral auxiliary.This approach could most likely also readily furnish the(+)-enantiomers of these germacrenes (of the germacraneterpenoid class) using the opposite enantiomer of the chiralauxiliary in the initial steps. <b>Keywords</b>: isoprenoids, natural product synthesis,allelochemicals, kairomones, allomones, bisabolane terpenoids,Hylobius abietis, germacrane terpenoids, Neodiprion sertifer,stereoselective synthesis.

<p>This thesis describes the synthetic preparation of somecompounds, which can serve as chemical signals for use in thedevelopment of control methods for pest insects. The compoundssynthesised are of the isoprenoid type and of two kinds:carvone derivatives and germacranes. The derivatives of carvoneare based on modifications of this compound, by reactions ofeither its endocyclic or its exocyclic double bond. One type ofmodifications was accomplished by chemoselective additions ofthiophenol. The latter ones imply additions to the exocyclicdouble bond and seem to constitute general, previously rarelystudied reactions.</p><p>In other modifications of its exocyclic side chain, carvoneafforded some sesqui- and diterpeniod natural products. Thefollowing compounds were synthesised in an enantioselectiveway: (-)-epi-delobanone, (-)-delobanone,(-)-7-hydroxy-3,10-prenylbisaboladien- 2-one (an insecticidalconstituent of Croton linearis) as well as its diastereomer andsome other compounds with similar structures. All of thesecompounds weretested for their antifeedant/feeding deterrentcapability against gnawing of the pine weevil, Hylobiusabietis.</p><p>The germacranes prepared by means of enantioselective totalsyntheses are: (–)- 1(10),5-germacradien-4-ol and(–)-germacrene D. The former is a constituent of thedefence secretion (an allomone) from the larvae of the pinesawfly, and the needles of Scots pine. (–)-Germacrene D isa ubiquitous compound in nature. For example, it occurs in thepeels of apples and acts as one component of a lure (akairomone) to the apples, which attracts the codling moth,Cydia pomonella.</p><p>The main problem in the total syntheses of the germacraneswas the formation of the unsaturated monocyclic 10-memberedring. This was achieved by intramolecular alkylation with asuitably functionalised/protected cyanohydrin derivative,which, after further elaboration, afforded a monocyclic10-membered enone, that was used in the syntheses of the twogermacranes mentioned above. In the initial steps in thesynthetic sequence the stereochemistry was established byalkylation of an amide enolate attached to a chiral auxiliary.This approach could most likely also readily furnish the(+)-enantiomers of these germacrenes (of the germacraneterpenoid class) using the opposite enantiomer of the chiralauxiliary in the initial steps.</p><p><b>Keywords</b>: isoprenoids, natural product synthesis,allelochemicals, kairomones, allomones, bisabolane terpenoids,Hylobius abietis, germacrane terpenoids, Neodiprion sertifer,stereoselective synthesis.</p>

<p>The interactions between plants and insects are mediated by volatile molecules. Plants respond to stress by biosynthesis of chemical substances which can deter invading insects or pathogens. Some of these substances are volatile and are emitted to the surroundings and may attract or repel insects. Information about the susceptibility of individual plants to infestation, their volatile emissions and chemical defence is of interest, for example in selecting plants for tree breeding programs.</p><p>This research was focused on finding volatile chemical markers of resistance in Norway spruce plants that do influence insects associated to conifers. Collection of headspace volatiles by SPME followed by separation and identification with GC-MS is effective in investigating biological systems with a minimum of disturbance. This method has here been used to investigate Norway spruce plants of different ages and stress conditions as well as trapping semiochemicals like nepetalactone emitted by the spruce shoot aphids. It was even possible to analyse the emission of single needles <i>in vivo</i> and obtain a chemical pattern of the site of the stress reaction. Seedlings of different ages showed differences in chemical composition of emitted volatiles, with the pine weevil repellent (<i>S</i>)-(-)-limonene as one of the main compounds. Wounded phloem of conventional plants emitted high amounts of monoterpenes while the phloem of mini plants emitted (3Z)-hexenal and (3Z)-hexen-1-ol.</p><p>Norway spruce plants did respond to different stress elicitors with similar response, regardless of their genetic origin. The emissions from stressed Norway spruce plants mainly consist of (<i>E</i>)-β-farnesene, (<i>E,E</i>)-α-farnesene, (<i>E</i>)-α-bisabolene, (<i>R</i>)-(-)-linalool and methyl salicylate. Emissions from live spruce shoot aphids were detected during autumn periods, and a method to separate and identify the four diastereomers of nepetalactone by GC-MS and characteristic m/z-fragments was accomplished.</p>

Lic.-avh. (sammanfattning) Alnarp : Sveriges lantbruksuniversitet, 2005. / Härtill 3 uppsatser.

The interactions between plants and insects are mediated by volatile molecules. Plants respond to stress by biosynthesis of chemical substances which can deter invading insects or pathogens. Some of these substances are volatile and are emitted to the surroundings and may attract or repel insects. Information about the susceptibility of individual plants to infestation, their volatile emissions and chemical defence is of interest, for example in selecting plants for tree breeding programs. This research was focused on finding volatile chemical markers of resistance in Norway spruce plants that do influence insects associated to conifers. Collection of headspace volatiles by SPME followed by separation and identification with GC-MS is effective in investigating biological systems with a minimum of disturbance. This method has here been used to investigate Norway spruce plants of different ages and stress conditions as well as trapping semiochemicals like nepetalactone emitted by the spruce shoot aphids. It was even possible to analyse the emission of single needles in vivo and obtain a chemical pattern of the site of the stress reaction. Seedlings of different ages showed differences in chemical composition of emitted volatiles, with the pine weevil repellent (S)-(-)-limonene as one of the main compounds. Wounded phloem of conventional plants emitted high amounts of monoterpenes while the phloem of mini plants emitted (3Z)-hexenal and (3Z)-hexen-1-ol. Norway spruce plants did respond to different stress elicitors with similar response, regardless of their genetic origin. The emissions from stressed Norway spruce plants mainly consist of (E)-β-farnesene, (E,E)-α-farnesene, (E)-α-bisabolene, (R)-(-)-linalool and methyl salicylate. Emissions from live spruce shoot aphids were detected during autumn periods, and a method to separate and identify the four diastereomers of nepetalactone by GC-MS and characteristic m/z-fragments was accomplished.

Molecular recognition has become a very important field of research in chemistry during the last decades. This<br />chemical phenomenon is responsible for all processes occurring in biology and asymmetric synthesis is based<br />upon the capability of molecules or substrates to recognise each other in a selective manner. In this thesis, the<br />design, preparation and evaluation of a series of new synthetic receptors has been described. The importance of<br />regioselectivity and stereoselectivity in molecular recognition has also been underlined with two different<br />biological examples.<br />The capability of host molecules, derived from (+)-tartaric acid, to accommodate various guests in a selective<br />manner was demonstrated using 1H-NMR spectroscopy (paper I). These host molecules, known as TADDOLs,<br />enantioselectively recognised the valuable chiral alcohols glycidol and menthol. Macromolecular receptors, i.e.<br />molecularly imprinted polymers (MIPs), were also prepared in order to catalyse the aldol reaction between either<br />(R)- or (S)-camphor and benzaldehyde (paper II). With the help of analytical methods, it was demonstrated that<br />the MIPs interacted in a selective manner with the enantiomers of camphor. Moreover, these MIPs enhanced<br />significantly the rate of the aldol condensation mentioned above.<br />Regarding biological systems, various regioisomeric analogues of benzoic acid have been tested as antifeedants<br />against the pine weevil Hylobius abietis (paper III and IV). The regioisomers studied displayed very different<br />antifeedant activities. The significance of stereoisomerism on pheromone function has been shown in the<br />preparation of lures for the control of the insect pest Argyrotaenia sphaleropa (paper V). It was demonstrated that<br />male leafrollers could be caught by a lure containing components of the female sex pheromone gland.

The large pine weevil, Hylobius abietis L., is a major insect pest on conifer seedlings in northern Europe. Due to its feeding newly planted trees get girdled, resulting in high seedling mortality (up to 80%). As a consequence great financial losses to the forest industry occur. Today the seedlings are protected with the pyrethroid insecticide cypermethrin. This insecticide is toxic to aquatic organisms and is, from 2010, prohibited for use in Sweden by the Swedish Chemicals Inspectorate. An alternative to insecticides is to protect the seedlings with antifeedants, compounds that, either through taste or smell or both, deter the weevils from feeding. This thesis describes the search for and the synthesis of such antifeedant compounds. Bark extracts of several woody species, known to be non-palatable to the weevil, were prepared and found to display antifeedant activity against H. abietis. The major chemical constituents of the extracts were tested for antifeedant activity. Antifeedants such as eugenol, 2-phenylethanol and benzylalcohol, but also feeding stimulants such as β-sitosterol and linoleic acid, were identified. An extract of linden bark, Tilia cordata, was shown to contain nonanoic acid, a highly active antifeedant. Other aliphatic carboxylic acids were also found to display high antifeedant activities against the weevil, both in laboratory and in field tests. The enantiomers of dihydropinidine, a piperidine alkaloid present in several conifer species, were prepared by dimethylzinc mediated allylation of 2- methyltetrahydropyridine-N-oxide. When tested in micro feeding assays, no difference in antifeedant activity was found for the enantiomers. In a field test high antifeedant activity, comparable with that of the presently used insecticide cypermethrin, was found for (±)-dihydropindine. Other naturally occurring piperidine alkaloids were synthesised and also found to display high antifeedant activities in laboratory tests. Structure-activity relationships were evaluated for methoxy substituted benzaldehydes, benzoic acids and cinnamic aldehydes, -acids, -esters and -alcohols. While the carboxylic acids were inactive or even feeding stimulants, the aldehydes were the most active antifeedants / QC 20110124

<p>The large pine weevil, Hylobius abietis L., is a major insect pest on conifer seedlings in northern Europe. Due to its feeding newly planted trees get girdled, resulting in high seedling mortality (up to 80%). As a consequence great financial losses to the forest industry occur. Today the seedlings are protected with the pyrethroid insecticide cypermethrin. This insecticide is toxic to aquatic organisms and is, from 2010, prohibited for use in Sweden by the Swedish Chemicals Inspectorate. An alternative to insecticides is to protect the seedlings with antifeedants, compounds that, either through taste or smell or both, deter the weevils from feeding. This thesis describes the search for and the synthesis of such antifeedant compounds.</p><p>Bark extracts of several woody species, known to be non-palatable to the weevil, were prepared and found to display antifeedant activity against H. abietis. The major chemical constituents of the extracts were tested for antifeedant activity. Antifeedants such as eugenol, 2-phenylethanol and benzylalcohol, but also feeding stimulants such as β-sitosterol and linoleic acid, were identified. An extract of linden bark, Tilia cordata, was shown to contain nonanoic acid, a highly active antifeedant. Other aliphatic carboxylic acids were also found to display high antifeedant activities against the weevil, both in laboratory and in field tests.</p><p>The enantiomers of dihydropinidine, a piperidine alkaloid present in several conifer species, were prepared by dimethylzinc mediated allylation of 2- methyltetrahydropyridine-N-oxide. When tested in micro feeding assays, no difference in antifeedant activity was found for the enantiomers. In a field test high antifeedant activity, comparable with that of the presently used insecticide cypermethrin, was found for (±)-dihydropindine. Other naturally occurring piperidine alkaloids were synthesised and also found to display high antifeedant activities in laboratory tests.</p><p>Structure-activity relationships were evaluated for methoxy substituted benzaldehydes, benzoic acids and cinnamic aldehydes, -acids, -esters and -alcohols. While the carboxylic acids were inactive or even feeding stimulants, the aldehydes were the most active antifeedants</p>

Norway spruce (Picea abies) responds to stress by biosynthesis of chemical substances, which can deter invading insects or pathogens. Some of these substances are volatile and can be emitted to the surroundings while others are accumulated within the tree. Information about the susceptibility of individual plants to infestation, their volatile emissions and chemical defence is of interest, for example, in selecting plants for tree breeding programs. The first part of this research focused on volatiles emitted by Norway spruce plants. Collection of headspace volatiles by SPME and subsequent separation and identification with GC-MS was used to investigate Norway spruce plants of different ages and stress conditions as well as trapping semiochemicals like nepetalactone emitted by the spruce shoot aphids. It was even possible to analyse the emission of single needles in vivo and obtain spatial localisation of the stress reaction to methyl jasmonate or spruce spinning mites. Seedlings of different ages showed differences in chemical composition of emitted volatiles, with the pine weevil repellent, (4S)-(-)-limonene, one of the main compounds. Wounded phloem of conventional plants emitted high amounts of monoterpenes while the phloem of mini plants emitted (3Z)-hexenal and (3Z)-hexen-1-ol. In addition, a method to separate and identify the four diastereomers of nepetalactone by GC-MS and characteristic m/z-fragments was accomplished. The second part of the research deals with the chemical response of Norway spruce roots to inoculation with Heterobasidion annosum. Terpene concentrations increased after inoculation or wounding but the composition was mainly associated with clone identity and not to susceptibility or treatment. In contrast, inoculation with H. annosum induced a treatment-specific alteration of phenol composition. The constitutive phenol composition differed between more and less susceptible clones. The phenols astringin and astringin dimers (piceasides) as well as the terpene α-longipinene may be suitable markers of low susceptibility for P. abies to Heterobasidion. / QC 20110314

The chemical elicitor methyl jasmonate (MeJA) could replace insecticides in Europe and Asia for protection of young conifers against the pine weevil (Hylobius abietis). This thesis mainly focuses on the effects of MeJA treatment on chemical defenses of conifers from seedling batches with documented field resistance. Tissues of three pine species and one spruce species, with various treatments, were here extracted in hexane, whereafter volatile contents of tissues were separated and analyzed by 2D GC-MS. Induced responses of seedlings of Maritime pine (Pinus pinaster) and Monterey pine (Pinus radiata) to the folivore pine processionary (Thaumetopoea pityocampa), and the phloem-feeder H. abietis, have been studied. Amounts of mono- and sesqui-terpenes (and also non-volatile resin) in conifer tissues (needles and phloem) were less induced by T. pityocampa than by H. abietis. The MeJA-treated seedlings of Scots pine (Pinus sylvestris) changed their composition of phloem monoterpenes (induction of (-)-β-pinene), and were better protected in field than the seedlings of Norway spruce (Picea abies), which increased their total amounts of monoterpenes. Orientation bioassays with H. abietis showed deterrent effects of (-)-β-pinene, (+)-3-carene, (-)-bornyl acetate and 1,8-cineole. Conversely, (-)-α-pinene (induced in P. abies but not in P. sylvestris) was non-deterrent. MeJA-treated seedlings fed on by H. abietis contained higher amounts of the H. abietis antifeedant 2-phenylethanol, in tissues and emissions. Phloem of control seedlings instead induced the (+)-α-pinene, which is one of the enantiomers of the H. abietis attractant α-pinene. In response to MeJA treatment, the relative amounts of the (+)-α-pinene increased in the phloem of  P. radiata, while it decreased in P. pinaster phloem. The preference of H. abietis in the field for P. radiata before P. pinaster may be explained by these changes in enantiomers of the H. abietis attractant α-pinene. / Barrträd är viktiga för skogsindustrin. I Sverige består 57% av ytan av produktiv skogsmark, och av dessa träd utgörs 80% av gran och tall. Som försvar mot insekter och sjukdomar, producerar barrträden kådämnen. För unga barrträd i Europa och Asien är snytbaggen (Hylobius abietis) en allvarlig skadegörare, som orsakar skogsnäringen stora kostnader. För att skydda små gran- och tallplantor före utplanteringen, skulle växthormonet metyljasmonat (MeJA) kunna användas. I denna avhandling har effekter av MeJA-behandling och insektsangrepp undersökts på de två viktigaste barrträden i Sverige, tall och gran (Pinus sylvestris och Picea abies) och på två arter i medelhavsområdet (Pinus radiata och Pinus pinaster). De kemiska försvarsämnena i barrträd har analyserats för att utvärdera effekterna av MeJA-behandling. Vävnader från barrträd med olika behandling har extraherats i organiska lösningsmedel och dofterna från plantorna har insamlats genom fastfas-mikroextraktion. De flyktiga ämnena har separerats och identifierats med hjälp av gaskromatografi och masspektrometri (GC-MS). Dessutom har optiskt aktiva doftämnen separerats med hjälp av en tvådimensionell GC-MS. Plantornas olika försvarsreaktioner har studerats vid angrepp av snytbaggen, som är en floemätare, och av tallfjärilslarv (Thaumetopoea pityocampa), som huvudsakligen äter barr. De lättflyktiga ämnena (mono- och seskviterpener) och de icke-flyktiga ämnena (kådsyror) ökade mer i stam och barr från angrepp av H. abietis än av T. pityocampa. Sammansättning av monoterpener ändrades i de MeJA-behandlade tallplantorna i Sverige, specifikt ökade (-)-β-pinene i stamfloemet. Tallplantorna var bättre skyddade i fält än granplantorna, där den totala mängden monoterpener ökade. (-)-β-Pinene, (+)-3-carene, (-)-bornyl acetate och 1,8-cineole visade sig ha en negativ effekt på snytbaggens orientering mot talldoft i orienteringstester. En av monoterpenerna, (-)-α-pinene, som av MeJA-behandlingen inducerats i granen, men inte i tallen, hade ingen negativ effekt på snytbaggen. MeJA-behandlade tallplantor som angripits av snytbaggen, innehöll större mängder av snytbagge-äthämmaren 2-fenyletanol, både i vävnader och i emissioner. Stam från kontrollplantor inducerade istället (+)-α-pinene, vilken är en av de optiska isomererna av snytbagge-attrahenten α-pinene. För de spanska arterna, som svar på MeJA-behandling, ökade de lättflyktigaste terpenerna i barren hos P. radiata men inte hos P. pinaster, vilken redan innehöll en hög terpenhalt. De relativa mängderna av (+)-α-pinene ökade också i stammen hos P. radiata, medan de minskade i P. pinaster. I fält väljer snytbaggen att gå till P. radiata- framför P. pinaster-plantor, vilket kan vara kopplat till de skillnader i α-pinene-isomerer, vilka här har observerats. / <p>QC 20160304</p>