Radical mediated stereoselective synthesis of (4R,8R)-4,8-dimethyldecanal, an aggregation pheromone of Tribolium flour beetles

(4R,8R)-4,8-Dimethyldecanal, a common aggregation pheromone of Tribolium flour beetles, has been synthesized from (R)-2,3-O-isopropylideneglyceraldehyde in 11 steps and 7% overall yield. The key step in the synthesis is the highly diastereoselective chelation-controlled radical reaction of ethyl (4S,5R)-4-benzyloxy-5,6-(isopropylidenedioxy)-2-methylenehexanoate with ethyl (R)-5-iodo-3-methylpentanoate performed in the presence of 7 equiv of MgBr₂·OEt₂.     

Pheromone synthesis. Part 243: Synthesis and biological evaluation of (3R,13R,1′S)-1′-ethyl-2′-methylpropyl 3,13-dimethylpentadecanoate, the major component of the sex pheromone of Paulownia bagworm, Clania variegata, and its stereoisomers

All of the four stereoisomers of (1′S)-1′-ethyl-2′-methylpropyl 3,13-dimethylpentadecanoate, the major component of the female sex pheromone of Clania variegata, were synthesized by employing olefin cross metathesis as the key reaction and starting from (R)- or (S)-2-methyl-1-butanol, (R)- or (S)-citronellal, and (S)-2-methyl-3-pentanol. Their bioassay revealed the (3R,13R,1′S)-isomer as the bioactive one, whose more efficient synthesis was achieved in two different ways by employing Wittig reaction as the key step.     

Synthesis of the Janus integer pheromone (4R,9Z)-9-octadecen-4-olide

The synthesis of (4R,9Z)-9-octadecen-4-olide 1, the female sex pheromone of Janus integer is reported using a Zipper isomerization reaction as the key step.     

Pheromone synthesis. Part 244: Synthesis of the racemate and enantiomers of (11Z,19Z)-CH503 (3-acetoxy-11,19-octacosadien-1-ol), a new sex pheromone of male Drosophila melanogaster to show its (S)-isomer and racemate as bioactive

The enantiomers of (11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol were synthesized from the enantiomers of 3,4-epoxy-1-butanol PMB ether. Its racemate was also synthesized. Its (S)-isomer and racemate were shown to possess the same pheromone activity as CH503, a long-lived inhibitor of male courtship in Drosophila melanogaster, although the racemate was less active.     

Synthesis of all the four stereoisomers of (1′S)-1-ethyl-2-methylpropyl 3,13-dimethylpentadecanoate, the major component of the sex pheromone of Paulownia bagworm, Clania variegata

All the four stereoisomers of (1′S)-1-ethyl-2-methylpropyl 3,13-dimethylpentadecanoate, the major component of the sex pheromone of Clania variegata, were synthesized by starting from (R)- or (S)-2-methylbutan-1-ol, (R)- or (S)-citronellal, and (S)-2-methylpentan-3-ol. Olefin cross metathesis was employed as the key reaction.     

Determination of the absolute configuration of the male aggregation pheromone, 2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol, of the stink bug Erysarcoris lewisi (Distant) as 2Z,6R,1′S,5′S by its synthesis

Lipase-catalyzed asymmetric acetylation of a mixture of (6R,1′S,4′S,5′R)- and (6R,1′R,4′R,5′S)-7′-norsesquisabinen-4′-ol (3) afforded a separable mixture of the recovered former and the acetate of the latter. The recovered alcohol was oxidized to (6R,1′S,5′R)-sesquisabina ketone (2), whose absolute configuration could be assigned by its CD comparison with (1R,5S)-sabina ketone (4). Conversion of (6R,1′S,5′R)-sesquisabina ketone (2) to the bioactive pheromone revealed the stereostructure of the male aggregation pheromone of the stink bug Erysarcoris lewisi (Distant) to be (2Z,6R,1′S,5′S)-2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol (sesquisabinen-1-ol, 1).     

Unsymmetrical double Wittig olefination on the syntheses of insect pheromones. Part 1: Synthesis of 5,9-dimethylpentadecane, the sexual pheromone of Leucoptera coffeella

An expeditious three-step synthesis of a mixture of stereoisomers of 5,9-dimethylpentadecane 1, the sexual pheromone of the coffee leaf miner Leucoptera coffeella, is described. The route employs an unsymmetrical double Wittig olefination to build the carbon skeleton of the molecule, as the key reaction. The bis-phosphonium salt 3, derived from 1,3-dibromopropane 2, reacted ‘one-pot’ with the ketones 2-octanone and 2-hexanone, affording the asymmetric diene 4. This was readily hydrogenated over Pd/C, furnishing pheromone 1 in 54% overall yield. Synthetic 1 showed high biological activity when tested in field experiments.     

Synthesis of all the stereoisomers of 6-methyl-2-octadecanone, 6,14-dimethyl-2-octadecanone, and 14-methyl-2-octadecanone, the components of the female-produced sex pheromone of a moth, Lyclene dharma dharma

All of the stereoisomers of the components of the female-produced sex pheromone of a moth, Lyclene dharma dharma, were synthesized. They are (R)- and (S)-6-methyl-2-octadecanone, (6R,14R)-, (6R,14S)-, (6S,14R)-, and (6S,14S)-6,14-dimethyl-2-octadecanone, and (R)- and (S)-14-methyl-2-octadecanone. Enantiomers of citronellal and methyl (S)-3-hydroxy-2-methylpropanoate were the starting materials, and olefin cross metathesis was employed as the key reaction.     

Absolute configuration of gomadalactones A, B and C, the components of the contact sex pheromone of Anoplophora malasiaca

Absolute configuration of gomadalactones A (1), B (2) and C (3), the pheromone components of the white-spotted longicorn beetle (Anoplophora malasiaca) was assigned as (1S,4R,5S)-1, (1R,4R,5R)-2 and (1S,4R,5S,8S)-3 by comparing their published CD spectra with those of (1R,5R)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]oct-7-ene-2,6-dione (4) and (1S,5R,8S)-(+)-4,4,8-trimethyl-3-oxabicyclo[3.3.0]octane-2,6-dione (5) prepared from (R)-(−)-carvone (6).     

Stereospecific synthesis of the sex pheromone of the passionvine mealybug, Planococcus minor

A short and completely stereospecific synthesis of (E)-2-isopropyl-5-methyl-2,4-hexadienyl acetate, the very recently identified sex pheromone of the passionvine mealybug Planococcus minor, is described. In the key step, CuI-catalyzed anti-addition of a Grignard reagent to a propargyllic alcohol intermediate gave the required trisubstituted alkene with 100% regio- and stereospecificity. The stereochemical purity of the pheromone is critically important because the (Z)-isomer is a powerful behavioral antagonist.     

Pheromone synthesis. Part 263: Synthesis of the racemate and the enantiomers of (E)-cis-6,7-epoxy-2-nonenal,the male-produced pheromone of the red-necked longhorn beetle,Aromia bungii

The racemate and the enantiomers of (E)-cis-6,7-epoxy-2-nonenal, the male pheromone of Aromia bungii, were synthesized by olefin cross metathesis between crotonaldehyde and (±)-, (+)- and (?)-cis-3,4-epoxy-7-octene. The epoxide was prepared by the Grignard coupling between allylmagnesium bromide and (±)-, (+)- and (?)-cis-2,3-epoxypentyl triflate. (±)-cis-2,3-Epoxy-1-pentanol was prepared by MCPBA epoxidation of (Z)-2-penten-1-ol, while its enantiomers were synthesized by the Sharpless asymmetric epoxidation of the allylic alcohol.     

Synthesis of a proposed structure for the diffusible extracellular factor of Xanthomonas campestris pv. campestris

A proposed structure for the diffusible extracellular factor (DF) of Xanthomonas campestris pv. campestris (Xcc) has been synthesized. Its MS spectrum and biological activity, however, contradict those of the natural product previously reported, suggesting that the structure for DF of Xcc must be reexamined.     

Pheromone synthesis. Part 264: Synthesis of the core 3-oxabicyclo[3.3.0]octane structures of gomadalactones A,B and C,the components of the contact sex pheromone of the white-spotted longicorn beetle,Anoplophora malasiaca

The core bicyclic cyclopentanelactone structures of gomadalactones A, B and C with α-hydroxyketone system were synthesized from (R)-pulegone, employing deconjugation of an α,β-unsaturated lactone as the key step. Comparison of the CD spectra of the synthetic compounds with those of the natural products confirmed the absolute configuration of the natural pheromone components as proposed in 2007. X-ray crystallographic analysis of the model compound of gomadalactone B core structure was carried out.     

Studies towards diarylheptanoid synthesis. Part 1: Synthesis and ring cleavage reactions of hexahydro-2H,5H-pyrano[2,3-b]pyran-2-ones

Lewis acid promoted anomeric substitution reactions of a stereoselectively prepared hexahydro-2H,5H-pyrano[2,3-b]pyran-2-one derivative was studied as a model for diarylheptanoid synthesis. Aromatic nucleophiles consistently provided the expected thermodynamic C-aryl pyranoside product.     

Gomadalactones A, B, and C: novel 3-oxabicyclo[3.3.0]octane compounds in the contact sex pheromone of the white-spotted longicorn beetle, Anoplophora malasiaca

The ether extract of the females of white-spotted longicorn beetle Anoplophora malasiaca showed activity as contact sex pheromone to males. The extract was fractionated, and a pheromonal activity was revealed only when three fractions; n-hexane, n-hexane/EtOAc 9:1, and EtOAc were blended. The relative structures of gomadalactone A, B, and C, three active components isolated from the EtOAc fraction, were determined by spectroscopic studies to be (1S^∗,4R^∗,5S^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-7-en-2,6-dione, (1R^∗,4R^∗,5R^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-7-en-2,6-dione, and (1S^∗,4R^∗,5S^∗,8S^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-2,6-dione, respectively.     

Synthesis of (2S,7S)-dibutyroxynonane, the sex pheromone of the orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), by diastereoselective silicon-tethered ring-closing metathesis

The sex pheromone of Sitodiplosis mosellana, (2S,7S)-dibutyroxynonane, has been synthesised using a mixed di-t-butylsilaketal prepared from (S)-5-hexen-2-ol and prochiral 1,4-pentadiene-3-ol. Ring-closing metathesis occurs diastereoselectively and after the removal of the silyl group and the reduction of the double bonds, generates (2S,7S)-nonanediol with a diastereoisomeric excess of 94% as measured by gas chromatographic analysis of the diacetylated product.     

Optically pure acyclic bifunctional compounds from (−)-menthone. Synthesis ofR-4-methyl-1-nonanol,the sex pheromone of the larger flour beetle (Tenebrio molitor L.)

A number of novel methyl-branched chirones were prepared starting from (–)-menthone and making use of a novel, efficient, and selective oxidant, decanepersulfonic acid (DPSA). Optically pure (4R)-methyl-1-nonanol, the sex pheromone of the larger flour beetle (Tenebrio molitor L.), was synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1301–1303, July, 1993.     

GCxGC/TOF MS technique-A new tool in identification of insect pheromones: Analysis of the persimmon bark borer sex pheromone gland

Conventional gas chromatography with electroantennographic detection (GC-EAD) and two-dimensional (GC × GC) gas chromatography using a time-of-flight mass spectrometric detector (TOFMS), were combined to analyse the female sex pheromone gland extract of the persimmon bark borer, Euzophera batangensis. GC-EAD analysis produced two EAD responses in GC areas where no compounds were detected by FID detection. GC × GC/TOFMS analysis of this area indicated the presence of several chemicals, including (Z9,E12)-tetradeca-9,12-dien-1-ol and (Z9)-tetradec-9-en-1-ol, pheromone components of closely related Euzophera species. Spectral characteristics, retention behaviour and the ability to elicit GC-EAD responses imply that both identified unsaturated alcohols are candidates for E. batangensis sex pheromone components. GC × GC/TOFMS facilitated the analysis of complex matrices on a subnanogram level and was shown to have great potential as a powerful tool in the analysis of insect pheromones.     

Simultaneous sampling and analysis of indoor air infested with Cimex lectularius L. (Hemiptera: Cimicidae) by solid phase microextraction,thin film microextraction and needle trap device

Air in a room infested by Cimex lectularius L. (Hemiptera: Cimicidae) was sampled simultaneously by three different sampling devices including solid phase microextraction (SPME) fiber coatings, thin film microextraction (TFME) devices, and needle trap devices (NTDs) and then analyzed by gas chromatography–mass spectrometry (GC–MS). The main focus of this study was to fully characterize indoor air by identifying compounds extracted by three different microextraction formats and, therefore, perform both the device comparison and more complete characterization of C. lectularius pheromone. The NTD technique was capable of extracting both (E)-2-hexenal and (E)-2-octenal, which were previously identified as alarm pheromones of bedbugs, and superior NTD recoveries for these two components allowed reliable identification based on mass spectral library searching and linear temperature programmed retention index (LTPRI) technique. While the use of DVB/CAR/PDMS SPME fiber coatings provided complementary sample fingerprinting and profiling results, TFME sampling devices provided discriminative extraction coverage toward highly volatile analytes. In addition to two alarm pheromones, relative abundances of all other analytes were recorded for all three devices and aligned across all examined samples, namely, highly infested area, less infested area, and control samples which were characterized by different bedbug populations. The results presented in the current study illustrate comprehensive characterization of infested indoor air samples through the use of three different non-invasive SPME formats and identification of novel components comprising C. lectularius pheromone, therefore, promising future alternatives for use of potential synthetic pheromones for detection of infestations.     

A convenient and new approach to the synthesis of ω-heterocyclic amino acids from carboxy lactams through ring-chain-transformation. Part 2: Synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid

Making use of amide activation, a convenient and short path synthesis of optically pure ω-heterocyclic-β-amino acids has been achieved from (1R,3R)- and (1R,3S)-5-oxo-1-(1-phenyl-ethyl)-pyrrolidine-3-carboxylic acid methyl ester. The key step of the synthesis involves a regiospecific ring-chain-transformation of the enaminones when subjected to 1,2-binucleophilic attacks. The method is illustrated by the synthesis of (2R)-/(2S)-2-aminomethyl-3-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)-propionic acid.