Synthesis Of Pheromone Research Articles

Enantioselective synthesis of mosquito oviposition pheromone and its epimer from a naturally occurring fatty acid

Direct epoxidation of cis-5-hexadecenoic acid towards the synthesis of Mosquito Oviposition Pheromone (MOP) and evaluation of Dynamic Kinetic Asymmetric Transformation (DYKAT) for late-stage asymmetric induction are presented.

Synthesis of corn rootworm pheromones from commercial diols

AbstractA mixture of stereoisomers of the corn rootworm pheromones was synthesised via the Grignard coupling of protected bromohydrins with alkylcuprate as a key step. The synthesis of 8-methyldec-2- yl propanoate (I ), the northern corn rootworm Diabrotica longicornis Say pheromone, was achieved from pentane-1,5-diol in four steps with an overall yield of 35.1 % and 10-methyltridecan-2-one (II ), the southern corn rootworm Diabrotica undecimpunctata howardi Barber pheromone, was synthesised from octane-1,8-diol as commercially available starting material in five steps with an overall yield of 28.7 %.

Acp70A regulates Drosophila pheromones through juvenile hormone induction

Mated Drosophila melanogaster females show a decrease in mating receptivity, enhanced ovogenesis, egg-laying and activation of juvenile hormone (JH) production. Components in the male seminal fluid, especially the sex peptide ACP70A stimulate these responses in females. Here we demonstrate that ACP70A is involved in the down-regulation of female sex pheromones and hydrocarbon (CHC) production. Drosophila G10 females which express Acp70A under the control of the vitellogenin gene yp1, produced fewer pheromones and CHCs. There was a dose-dependent relationship between the number of yp1-Acp70A alleles and the reduction of these compounds. Similarly, a decrease in CHCs and diene pheromones was observed in da > Acp70A flies that ubiquitously overexpress Acp70A. Quantitative-PCR experiments showed that the expression of Acp70A in G10 females was the same as in control males and 5 times lower than in da > Acp70A females.Three to four days after injection with 4.8 pmol ACP70A, females from two different strains, exhibited a significant decrease in CHC and pheromone levels. Similar phenotypes were observed in ACP70A injected flies whose ACP70A receptor expression was knocked-down by RNAi and in flies which overexpress ACP70A N-terminal domain. These results suggest that the action of ACP70A on CHCs could be a consequence of JH activation. Female flies exposed to a JH analog had reduced amounts of pheromones, whereas genetic ablation of the corpora allata or knock-down of the JH receptor Met, resulted in higher amounts of both CHCs and pheromonal dienes.Mating had negligible effects on CHC levels, however pheromone amounts were slightly reduced 3 and 4 days post copulation. The physiological significance of ACP70A on female pheromone synthesis is discussed.

(4S,6R)-4-methyl-6-pentyltetrahydro-2H-pyran-2-one as an efficient intermediate in the preparation of chiral building blocks with methyl-branched carbon skeleton. Application to the synthesis of bioactive compounds

Synthesis was performed of (3S)-3-methyldecen-1-ol and (4S)-4-methylundecen-1-ol, chiral alcohols with a methyl-branched carbon skeleton. The possibility of their application in asymmetric syntheses of insect pheromones was demonstrated.

(5S)-5-hydroxy-3-methylidenehexanoate as key intermediate in synthesis of tetrahydrolipstatin and pheromone of oriental hornet Vespa Orientalis

Proceeding from the readily available methyl (5S)-5-hydroxy-3-methylidenehexanoate obtained by the reaction of asymmetric allylation a new approach has been developed to the preparation of (6S)-6-undecyl-5,6-dihydro-2H-pyran-2-one which has underlain the synthesis of (6S)-6-undecyltetrahydro-2H-pyran-2-one, the pheromone of oriental hornet Vespa Orientalis, and also the formal synthesis of the tetrahydrolipstatin, a drug for weight loss.

Sexual selection in true fruit flies (Diptera: Tephritidae): transcriptome and experimental evidences for phytochemicals increasing male competitive ability.

In male tephritid fruit flies of the genus Bactrocera, feeding on secondary plant compounds (sensu lato male lures=methyl eugenol, raspberry ketone and zingerone) increases male mating success. Ingested male lures alter the male pheromonal blend, normally making it more attractive to females and this is considered the primary mechanism for the enhanced mating success. However, the male lures raspberry ketone and zingerone are known, across a diverse range of other organisms, to be involved in increasing energy metabolism. If this also occurs in Bactrocera, then this may represent an additional benefit to males as courtship is metabolically expensive and lure feeding may increase a fly's short-term energy. We tested this hypothesis by performing comparative RNA-seq analysis between zingerone-fed and unfed males of Bactrocera tryoni. We also carried out behavioural assays with zingerone- and cuelure-fed males to test whether they became more active. RNA-seq analysis revealed, in zingerone-fed flies, up-regulation of 3183 genes with homologues transcripts to those known to regulate intermale aggression, pheromone synthesis, mating and accessory gland proteins, along with significant enrichment of several energy metabolic pathways and gene ontology terms. Behavioural assays show significant increases in locomotor activity, weight reduction and successful mating after mounting; all direct/indirect measures of increased activity. These results suggest that feeding on lures leads to complex physiological changes, which result in more competitive males. These results do not negate the pheromone effect, but do strongly suggest that the phytochemical-induced sexual selection is governed by both female preference and male competitive mechanisms.

The effect of artificial diet on the production of alarm pheromone by Myzus persicae

AbstractThe cornicle secretion of Myzus persicae reared on artificial diet only elicits an alarm response in plant‐reared conspecifics after the young aphids have been transferred to plants for 7 days. Acetate in the form of 0.32% sodium acetate has been added to the diet as an early step in synthesis of the alarm pheromone, (E)‐β‐farnesene (EBF). The cornicle secretion of diet‐reared aphids then elicits an alarm response. However, there is no difference in internal EBF concentration between plant‐ and diet‐reared aphids. Puncturing aphids, either plant‐ or diet‐reared, with a pin shows that both can elicit an alarm response, whereas it is reduced by half with diet‐reared individuals. Although there is no significant difference in the concentration of EBF produced, the total amount in diet‐reared aphids is increased by acetate in the diet to a level similar to that in plant‐reared individuals: the size of aphids reared on an acetate‐supplemented diet is increased and comparable with the size of those that are plant‐reared. Bioassays with a range of EBF concentrations show a high threshold for the alarm response. It is concluded that the different size of aphids reared on plants and standard diet results in them secreting, respectively, above and below the response threshold.

Cuelure but not zingerone make the sex pheromone of male Bactrocera tryoni (Tephritidae: Diptera) more attractive to females

In tephritid fruit flies of the genus Bactrocera Macquart, a group of plant derived compounds (sensu amplo ‘male lures’) enhance the mating success of males that have consumed them. For flies responding to the male lure methyl eugenol, this is due to the accumulation of chemicals derived from the male lure in the male rectal gland (site of pheromone synthesis) and the subsequent release of an attractive pheromone. Cuelure, raspberry ketone and zingerone are a second, related group of male lures to which many Bactrocera species respond. Raspberry ketone and cuelure are both known to accumulate in the rectal gland of males as raspberry ketone, but it is not known if the emitted male pheromone is subsequently altered in complexity or is more attractive to females. Using Bactrocera tryoni as our test insect, and cuelure and zingerone as our test chemicals, we assess: (i) lure accumulation in the rectal gland; (ii) if the lures are released exclusively in association with the male pheromone; and (iii) if the pheromone of lure-fed males is more attractive to females than the pheromone of lure-unfed males. As previously documented, we found cuelure was stored in its hydroxyl form of raspberry ketone, while zingerone was stored largely in an unaltered state. Small but consistent amounts of raspberry ketone and β-(4-hydroxy-3-methoxyphenyl)-propionic acid were also detected in zingerone-fed flies. Males released the ingested lures or their analogues, along with endogenous pheromone chemicals, only during the dusk courtship period. More females responded to squashed rectal glands extracted from flies fed on cuelure than to glands from control flies, while more females responded to the pheromone of calling cuelure-fed males than to control males. The response to zingerone treatments in both cases was not different from the control. The results show that male B. tryoni release ingested lures as part of their pheromone blend and, at least for cuelure, this attracts more females.

Cyclopropane intermediates in the synthesis of chiral alcohols with methyl-branched carbon skeleton. Application in the synthesis of insect pheromones

Several chiral building blocks, (2R)-2-methylundec-10-en-1-ol, (3R)-3-methylheptan-1-ol, and (4R)-4-methyloctan-1-ol, have been synthesized using cyclopropane intermediate products. It has been shown that the obtained chiral alcohols can be used in the synthesis of insect pheromones.

Pheromone synthesis. Part 255: Synthesis and GC–MS analysis of pheromonal triacylglycerols of male Drosophila fruit flies

Pheromonal triacylglycerols and their analogs, 1A, 1B, 2A, 2B, 3A, 3B, and 3C, of male Drosophila fruit flies were synthesized and analyzed by GC–MS. Their GC retention times were found to be a reliable measure to analyze and identify these triacylglycerols with acetyl, oleoyl and tigloyl groups, although the stereo- and regioisomers of 1 (1A and 1B), 2 (2A and 2B), and 3 (3A, 3B, and 3C) could not be distinguished from each other by MS alone.

Unexpected functional diversity in the fatty acid desaturases of the flour beetle Tribolium castaneum and identification of key residues determining activity

Desaturases catalyse modifications to fatty acids which are essential to homeostasis and for pheromone and defensive chemical production. All desaturases of the flour beetle Tribolium castaneum were investigated via query of the sequenced genome which yielded 15 putative acyl-Coenzyme A genes. Eleven desaturase mRNA were obtained in full length and functionally expressed in yeast. Phylogenetic analysis separated the desaturases into 4 distinct clades; one clade contained conserved beetle Δ9 desaturases, second clade was Tribolium-specific having diverse activities including Δ5, Δ9 and Δ12 desaturation and the other 2 clades had mixed insect representatives. Three members of this clade contained unusual inserted sequences of ∼20 residues in the C-terminal region and were related to desaturases that all contained similar inserts. Deletion of the entirety of the insert in the flour beetle Δ12 desaturase abolished its activity but this was partially restored by the reintroduction of two histidine residues, suggesting the histidine(s) are required for activity but the full length insert is not. Five new desaturase activities were discovered: Δ9 desaturation of C12:0–C16:0 substrates; two unprecedented Δ5 enzymes acting on C18:0 and C16:0; Δ9 activity exclusively on C16:0 and a further stearate Δ9 desaturase. qPCR analysis ruled out a role in sex pheromone synthesis for the Δ5 and Δ9/C16:0 desaturases. The flour beetle genome has underpinned an examination of all transcribed desaturases in the organism and revealed a diversity of novel and unusual activities, an improved understanding of the evolutionary relationships among insect desaturases and sequence determinants of activity.

Putative pathway of sex pheromone biosynthesis and degradation by expression patterns of genes identified from female pheromone gland and adult antenna of Sesamia inferens (Walker).

The general pathway of biosynthesis and degradation for Type-I sex pheromones in moths is well established, but some genes involved in this pathway remain to be characterized. The purple stem borer, Sesamia inferens, employs a pheromone blend containing components with three different terminal functional groups (Z11-16:OAc, Z11-16:OH, and Z11-16:Ald) of Type-I sex pheromones. Thus, it provides a good model to study the diversity of genes involved in pheromone biosynthesis and degradation pathways. By analyzing previously obtained transcriptomic data of the sex pheromone glands and antennae, we identified 73 novel genes that are possibly related to pheromone biosynthesis (46 genes) or degradation (27 genes). Gene expression patterns and phylogenetic analysis revealed that one desaturase (SinfDes4), one fatty acid reductase (SinfFAR2), and one fatty acid xtransport protein (SinfFATP1) genes were predominantly expressed in pheromone glands, and clustered with genes involved in pheromone synthesis in other moth species. Ten genes including five carboxylesterases (SinfCXE10, 13, 14, 18, and 20), three aldehyde oxidases (SinfAOX1, 2 and 3), and two alcohol dehydrogenases (SinfAD1 and 3) were expressed specifically or predominantly in antennae, and could be candidate genes involved in pheromone degradation. SinfAD1 and 3 are the first reported alcohol dehydrogenase genes with antennae-biased expression. Based on these results we propose a pathway involving these potential enzyme-encoding gene candidates in sex pheromone biosynthesis and degradation in S. inferens. This study provides robust background information for further elucidation of the genetic basis of sex pheromone biosynthesis and degradation, and ultimately provides potential targets to disrupt sexual communication in S. inferens for control purposes.

Catalytic asymmetric synthesis of the Colorado potato beetle pheromone and its enantiomer

An efficient catalytic asymmetric synthesis of the CPB pheromone [(S)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one] and its enantiomer was accomplished with 99% ee and in gram quantities from geraniol. The key steps in this procedure involve Sharpless asymmetric epoxidation and recrystallization of the 4-bromobenzoate from the CPB pheromone to improve its enantiomeric purity. Furthermore, the absolute configuration of the CPB pheromone enantiomer was confirmed as (R) for the first time by the X-ray crystallographic structure of its benzoate.

Stereochemical Aspects of Pheromonal Communications: Diversity is the Key Word

The relationships between stereochemistry and bioactivity of pheromones are not simple but complicated, and a naturally occurring pheromone is not always the most bioactive stereoisomer. Pheromones are not necessarily stereochemically pure, and they are sometimes a mixture of stereoisomers. In 1973 when I started my pheromone synthesis, almost nothing was known about stereochemistry of pheromones. The reason was that conventional methods for determining their absolute configuration, such as degradation to a known chiral molecule or X-ray analysis, could not be useful in the case of pheromones, because they were usually oils secured in extremely minute amounts. My synthesis of (S)-(+)-trogodermal in 1973 resulted in the assignment of the R-configuration to the naturally occurring (−)-trogodermal, the pheromone of Trogoderma grain beetles. Since then enantioselective synthesis of a pheromone has become the standard method for the determination of its absolute configuration (Mori 2007). My 1974 synthesis of the enantiomers of exo-brevicomin was soon followed by the synthesis of the enantiomers of frontalin in 1975. Their pheromone activity was examined against the western pine beetle by David Wood, who found that only (1R,5S,7R)-(+)-brevicomin and (1S,5R)-(−)frontalin were bioactive. This was the beginning of a long and still continuing journey to clarify the significance of chirality in chemical communication.

(3S,5R)-6-(benzyloxy)-3-methylhexane-1,5-diol in the synthesis of insect pheromones with methyl-branched carbon chain and of amphidinolide L C 7 –C 14 fragment

New building block (3S,5R)-6-(benzyloxy)-3-methylhexane-1,5-diol was obtained, and based thereon new formal syntheses of (Z)-trogodermal, a component of the sex pheromone of smaller tea tortrix and of the alarm pheromone of ants of genus Crematogaster were suggested. A new synthetic protocol for (3S)-5-methyl-5-oxopentyl acetate and (3S)-5-(benzyloxy)-3-methylpentanal, convenient building blocks for insect pheromones designing was developed. A new simple and efficient asymmetric synthesis of C7–C14 fragment of the cytotoxic macrolactone amphidinolide L was carried out.

Simple Synthesis of (Z)-7-Eicosen-11-one- the Sex Pheromone of Peach Fruit Moth

Peach fruit moth is one of the most serious pests, whose sex pheromone is (Z)-7-eicosen-11-one. Synthesis of the compound was achieved from 2,3-dihydrofuran. Firstly, acidic hydrolysis of 2,3-dihydrofuran gave 4-hydroxybutanal, which reacted with the ylide prepared from heptyltriphenylphosphonium bromide to afford (Z)-4-undecen-1-ol. The alcohol was oxi- dated followed by Grignard addition and further oxidation to give the target product. Keywords carposina sasakii matsumura; (Z)-7-eicosen-11-one; pheromone synthesis; Wittig reaction; Grignard addition

Diastereodivergent total synthesis of mosquito oviposition pheromone

The unnatural threo-6-acetoxy-5-hexadecanolide and the natural mosquito oviposition pheromone erythro-6-acetoxy-5-hexadecanolide were synthesized in a diastereodivergent fashion in 44% and 33% overall yield respectively from 5-bromovaleric acid and undecanal. The key step utilized a chemoenzymatic epoxidation-lactonization of a naturally available fatty acid to form the 6-hydroxy-5-hexadecanolide core.

Enzymatic synthesis of a chiral chalcogran intermediate

AbstractTwo lipases, Novozyme 435 (lipase B from Candida Antarctica) and Lipozyme TL IM (Thermomyces lanuginosus) were used successfully for the kinetic resolution of racemic 1-(2-furyl)-3-pentanol, the key intermediate in synthesis of the bark beetle pheromone, chalcogran. The desired S-(+)-enantiomer was prepared in enantiomeric excesses higher than 98 % and with yields of 26.3 % and 32.5 %, respectively. Methyl tert-butyl ether and vinyl acetate were found to be the best reaction media and the acetyl donor to achieve fast and effective resolution.

ChemInform Abstract: Methyl (3R,5R)‐3,5‐Dihydroxydecanoate in the Asymmetric Synthesis of Idea Leuconoe Pheromone and Formal Syntheses of (+)‐(3R,5R)‐3‐Hydroxydecano‐5‐lactone, Verbalactone, and Tolypothrix Pentaether.

AbstractAn asymmetric synthesis of (IV) is outlined which is one of the numerous components of the abdominal gland secretion of the giant danaine butterfly idea leuconoe.

Pheromone Communication inAnastrepha obliqua(Diptera: Tephritidae): A Comparison of the Volatiles and Salivary Gland Extracts of Two Wild Populations

The West Indian fruit fly Anastrepha obliqua Macquart (Diptera: Tephritidae) is one of the major pests on mango (Mangifera indica L.; Sapindales: Anacardiaceae) and starfruit (Averrhoa carambola L.; Oxalidales: Oxalidaceae) crop plantations in Brazil. Pheromone communication inter alia plays an important role in fruit-fly courtship behavior. In order to highlight the site of pheromone synthesis, we identified and compared the volatiles from the aeration extracts of calling males with the volatiles produced by their salivary glands in 2 wild populations of A. obliqua collected from mangoes and starfruits. In addition, we performed a series of bioassays to compare the biological significance of both extracts. In total, 36 volatile compounds were identified, with 8 of them being shared by the 2 populations and the 2 extract types. Linalool and α-copaene were exclusively found in the aeration extract while ethyl heptanoate, methyl octanoate, and 1-nonanol were detected only in the salivary-gland extracts. The chemical profiles of the volatiles from the aeration extracts and from the salivary-gland extracts differed significantly between the 2 populations as well as the chemical profiles of both extracts within each population. The quantities of the 8 shared compounds generated a variability of more than 60% in the mango population and 80% in the starfruit population. The similarities observed between the chemical profiles of the aeration extracts and the salivary-gland extracts suggest that the latter could be the storage site and probably also the production site of some pheromone components in this fruit-fly species. This hypothesis is supported by the comparable biological activities of both extracts in terms of their attractiveness for conspecific females.