The Absolute Configuration of the Sex Pheromone of the Citrophilous Mealybug, <Emphasis Type="Italic">Pseudococcus calceolariae</Emphasis>

The absolute configuration of the sex pheromone of the citrophilous mealybug, Pseudococcus calceolariae, was determined to be (1R,3R)-[2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropyl]methyl (R)-2-acetoxy-3-methylbutanoate. NMR, derivatization reactions, chiral gas chromatography-mass spectrometry, and comparison with synthetic chiral reference compounds, were used to determine the absolute configuration of this compound. This activity of this compound was further confirmed by testing synthetic stereoisomers of the compound as lures in traps for adult male mealybugs. Traps baited with 1,000 μg of the pheromone compound caught 36 times more males than traps baited with virgin females. A mixture of stereoisomers of the pheromone compound can be used for field trapping without adverse effects on trap catch. A comparison with the structures of other sex pheromones of mealybugs is presented.     

Purification,Stereoisomeric Analysis and Quantification of Sex Pheromone Precursors in Female Whole Body Extracts from Pine Sawfly Species

A GC-MS method to analyze the stereoisomeric composition of chiral secondary alcohols found in whole body extracts of pine sawfly females was developed. The tested alcohols were derivatized with optically pure (S)-2-acetoxypropionyl chloride prior to GC-MS analysis. Baseline separation was obtained for all sixteen stereoisomers of 3,7,9-trimethyltridecan-2-ol and for the four 3-methylpentadecan-2-ol stereoisomers. For 3,7-dimethyltridecan-2-ol, 3,7-dimethyltetradecan-2-ol and 3,7-dimethylpentadecan-2-ol baseline separation was obtained for 6 of the possible 8 stereoisomers. When a mixture of 16 stereoisomers of 3,7,11-trimethyltridecan-2-ol was tested, baseline separation of 7 peaks out of 16 possible was obtained. The investigated alcohols are pheromone precursors for some pine sawfly species that are severe defoliators of pine. Females from several Diprion, Neodiprion, Macrodiprion, Microdiprion, and Gilpinia species emit esters of such secondary alcohols as sex pheromones that attract males for mating. To quantify the small amounts of the precursor alcohol and its stereoisomeric composition found in whole body extracts from female pine sawflies, a purification method was optimized. An extract of 20 females of D. pini contained about 8 ng of (2S,3R,7R)-3,7-dimethyltridecan-2-ol per female, and three extracts of 18, 20, and 90 females of N. sertifer contained between 5 and 13 ng of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol per female.     

Determination of the Absolute Configuration of the Male-Produced Sex Pheromone of the Stink Bug Pellaea stictica, (2R,4R,8R)-2,4,8,13-Tetramethyltetradecan-1-ol by Stereoselective Synthesis Coupled with Enantiomeric Resolution

In a previous study, we reported the identification and synthesis of a male-specific sex pheromone component of the stink bug, Pellaea stictica, as the alcohol 2,4,8,13-tetramethyltetradecan-1-ol (1). To establish the correlation between the stereochemistry of the pheromone and its bioactivity, it first was necessary to determine its absolute configuration. For this purpose, a series of syntheses were designed to: (a) furnish a mixture of all possible stereoisomers; (b) a narrowed down group of diastereomers, and (c) one specific enantiomer. A crucial step in the syntheses involved a coupling reaction between two key intermediates: a phosphonium salt and an aldehyde, through a Wittig olefination. Nuclear magnetic resonance data of a mixture of the synthetic pheromone diastereomers and further comparison of GC retention times with that of the natural product by gas chromatography suggested that the methyl branches at C2 and C4 were in a syn relationship, reducing the possibilities to only four of the eight possible stereoisomers. Employing GC analysis, chiral derivatization reagents and synthetic (8R)-2,4-syn-1 it was possible to confirm the configuration of the methyl branch at C8 as R, reducing the number of possible stereoisomers to two. After enantioselective synthesis of (2R,4R,8R)-1, the absolute configurations of all methyl branches of the natural compound were confirmed as R, fully identifying the male-produced sex pheromone of P. stictica as (2R,4R,8R)-2,4,8,13-tetramethyltetradecan-1-ol.

     

Chirality of israeli pine bast scale,Matsucoccus josephi (homoptera: Matsucoccidae) sex pheromone

The absolute configuration of the sex pheromone of the Israeli pine bast scale,Matsucoccus josephi, was determined as (2E,5R,6E,8E)-5,7-dimethyl-2,6,8-decatrien-4-one, designated here asR-E with 10% (2E,5S,6E,8E)-5,7-dimethyl-2,6,8-decatrien-4-one, designated asS-E. The chirality of the quantitatively minorZ isomer was (2E,5R,6Z,8E)-5,7-dimethyl-2,6,8-decatrien-4-one (R-Z). Chiral assignments were made by comparative gas chromatographic (GC) analysis of naturalM. josephi pheromone with stereoselectively synthesized stereoisomers on a chiral Cyclodex-B column, which separated the enantiomers with baseline resolution. In gas chromatographic-electroantennographic detection (GC-EAD) analysis of the racemicZ andE isomers, the latter elicited the stronger antennal response by maleM. josephi. In GC-EAD of all four stereoisomers, employing the chiral column,R-E was the most active stereoisomer. In field testsR-E attracted 10 times more males ofM. josephi than didS-E. The racemicE/Z pheromone mixture, containing all four stereoisomers in approximately equal amounts, attracted as many maleM. josephi as did an equivalent amount ofR-E, indicating that the other stereoisomers are not inhibitory. The same keto-diene moiety with the same chiral center and configuration in all three known Matsucoccidae sex pheromones implies a common biosynthetic pathway and phylogenetic relationship.Contribution from the Agricultural Research Organization, the Volcani Center, No. 1496-E, 1994 series.Part of the work was performed during a sabbatical leave of E.D. at Simon Fraser University.     

Cinnamomeoventrolide – Double Bond Regioisomerism in Frog Semiochemicals

Frogs of the families Mantellinae and Hyperoliidae possess male specific femoral or gular glands that are used during courtship. These glands release volatile compounds, e. g. the macrocyclic lactone gephyromantolide A (2,6,10-trimethyl-6-undecen-11-olide) in the case of Gephyromantis boulengeri (Mantellinae). During the analysis of the volatiles of Hyperolius cinnamomeoventris (Hyperoliidae) we detected an unknown compound A, which we called cinnamomeoventrolide, whose mass spectrum showed high similarity with the spectrum of gephyromantolide A. Nevertheless, slight spectral differences led to the proposal of a regioisomer of gephyromantolide A as a structure for A, 2,6,10-trimethyl-5-undecen-11-olide. A versatile synthesis of this compound was developed to allow access to all four stereoisomers from a single chiral starting material, the so-called (S)-Roche ester, using ring-closing metathesis as a key step. With these stereoisomers, the absolute configuration of the natural product was established to have the (2R,10S)-configuration by GC on a chiral phase. The configuration of natural gephyromantolide A is the opposite. Both frogs seem to use a similar biosynthetic pathway to access the target compounds, differing in the stereochemistry of the reduction steps, and requiring an additional isomerization in case of G. boulengeri. This unique regioisomeric differentiation of double bonds in semiochemicals has so far only been observed in insects. The compounds are likely to play a role in species-recognition of the frogs.

     

Synthesis of the stereoisomers of the female sex pheromone of the Hessian fly,Mayetiola destructor

The female-produced sex pheromone of the Hessian fly,Mayetiola destructor (Say) (Diptera: Cecidomyiidae), has been identified as (10E)-tridecen-2-yl acetate. A flexible synthetic route was developed which allowed access to the chiral and racemic forms of the pheromone, and to the 10Z stereoisomer of the pheromone. The natural compound was determined to have the 2S configuration by hydrolysis of the acetate function, derivatization of the resulting alcohol with (2S)-2-acetoxypropionyl chloride, and capillary gas Chromatographic comparison of the derivative with the corresponding derivatives prepared from the synthetic enantiomers. Trace amounts of the 10Z isomer of the pheromone have also been detected in extracts of female Hessian fly ovipositors, along with (10E)-tridecen-2-ol and 2-tridecanyl acetate. Due to the small quantities of these compounds available from ovipositor extracts, the chirality of the trace components has not yet been determined.     

Quantitative high-resolution gas chromatographic determination of stereoisomeric composition of chiral volatile compounds in the picogram range by ec-detection

A gas chromatographic method using electron capture detection for determination of the stereochemical composition of chiralolatile compounds, e.g., pheromones, at the picogram level is described. Substances of interest are analyzed as pentafluorobenzoate derivatives on fused silica capillary columns coated with CP Sil-88. This method was developed primarily for the quantitative analyses of stereoisomerism of the pheromone precursor, diprionol, in female sawflies,Neodiprion sertifer. It was possible to separate the stereoisomers showing (2S, 3S, 7R) and (2S, 3S, 7S) configurations. Resolution of the (2S, 3S, 7S)- and (2S, 3R, 7R)-diastereomers was high enough to allow the quantification of these stereoisomers. A quantitative analysis of the diprionol production in individualN. sertifer females yielded 7.5–9.7 ng/female.     

Effect of the Chiral Center Position of an Optically Active Terminal Group on the Induction of Optical Activity in Polysilanes

Summary Polysilanes with an optically active alkoxy group, i.e., (S)-(+)-2-butoxy, (R)-(-)-2-butoxy, (S)-(-)-2-methyl-1-butoxy, and (S)-(+)-3,7-dimethyl-1-octoxy, at the terminal positions, the chiral carbon centers of which were located at the α, β, and γ positions relative to the oxygen, respectively, were prepared, and the effect of the position of chiral center of the terminal optically active group on the induction of optical activity in polysilanes was investigated. The circular dichroism (CD) spectra of these polymers showed positive Cotton signals around 340 nm at temperatures below -20 °C, but the intensities were small, indicating that the optically active groups at the terminal positions have some ability, albeit small, to induce optical activity to the polysilanes. Further, the optically active (S)-(+)-2-butoxy and (R)-(-)-2-butoxy groups did not control the helical sense direction of the polymers, despite the different chiral stimuli from the 2-butoxy groups introduced to the terminal positions. To control the helical structure of polysilanes by the use of optically active terminal groups, appropriate optically active groups are required.     

Enantioselective Synthesis of Chiral Homoallyl Alcohols and Homoallylamines by Nucleophilic Addition of an Allylboron Reagent Modified by a Polymer‐Supported Chiral Ligand

Crosslinked polymer‐supported chiral N‐sulfonylamino alcohols 5–8 have been prepared by suspension polymerization of enantiopure N‐sulfonylamino alcohol monomers 1–4 with styrene and divinylbenzene. Polymer‐supported chiral allylboron reagents were prepared from the polymeric chiral ligands. Enantioselective additions of the polymer‐supported allylboron reagents to aldehydes and N‐(trimethylsilyl)imines have been successfully carried out in the heterogeneous system. The corresponding optically active homoallyl alcohols and homoallylamines were obtained in high yields with high enantioselectivities (up to 95% ee) which are almost the same as those obtained from homogeneous analogues. The polymer‐supported chiral ligands used were recovered easily and can be reused without any loss of activity.     

Molecular Recognition of the HPLC Whelk-O1 Selector towards the Conformational Enantiomers of Nevirapine and Oxcarbazepine

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy.     

Synthesis of Optically Active Dendrimers Having Chiral Bisphosphine as a Core

Summary First and second generation chiral dendrimers P-1G1, P-2G1, P-1G2 and P-2G2 containing chiral bisphosphine as a core were synthesized via a reaction of chiral bisphosphine compound (S,S)-1 with benzyl ether dendrons. This is the first example of chiral dendrimers containing chiral phosphorus atoms. To investigate the effect of chiral phosphorus atoms on their conformations, optically inactive dendrimer P′-2G1 was synthesized as well using optically inactive initiator 1′ which was the mixture of rac-1 ((S,S)-1 and (R,R)-1) and meso-1. Their structures were characterized by ¹H, ¹³C, ³¹P NMR, and HRMS. According to CD measurement, optically active dendrimers exhibited the Cotton effect induced by the chirality of phosphorus atoms, while optically inactive dendrimer P′-2G1 showed no Cotton effect.     

Novel type of sex pheromone structure identified fromStigmella malella (Stainton) (Lepidoptera: Nepticulidae)

Short-chain unsaturated chiral methyl carbinols are identified as a new class of lepidopteran pheromone components. The natural female-produced pheromone of the banded apple pigmyStigmella malella (=Nepticula malella) (Stainton) (Lepidoptera: Nepticulidae) was identified to be a mixture of (S)-(E)-6,8-nonadien-2-ol and (S)-(Z)-6,8-nonadien-2-ol. For monitoring traps, a 10:3E:Z blend at 100–1000 µg is recommended. It is suggested that pheromones with similar structures may be specific to Nepticulidae and other related microlepidopteran families.     

Resolution of Epoxydienes by Reversed-Phase Chiral HPLC and its Application to Stereochemistry Assignment of Mulberry Looper Sex Pheromone

Resolution of insect pheromonal cis-epoxydiene racemates derived from (Z,Z,Z)-3,6,9-trienes was examined with a reversed-phase chiral HPLC column. The results showed that a Chiralcel OJ-R column was suitable for separating the enantiomers having a C₁₇–C₂₃ unsaturated straight chain except for 9,10-epoxydienes with a C₂₁–C₂₃ chain. To determine the absolute configuration of the separated enantiomers, each of the optically active epoxydienes was hydrogenated over Pd-BaSO₄ and its behavior was examined on this chiral column by cochromatography with the corresponding chiral epoxy compound having a saturated chain, which was prepared via a Sharpless epoxidation reaction. This analysis showed that the dextrorotatory C₁₇–C₂₃ 3,4- and 6,7-epoxydienes and C₁₇–C₂₀ 9,10-epoxydienes with shorter R _ts possess (3S,4R)-, (6S,7R)-, and (9R,10S) configurations, respectively, and the levorotatory enantiomers with longer R _ts possess the opposite configuration. An abdominal tip extract of the mulberry looper, Hemerophila artilineata Butler (Lepidoptera: Geometridae: Ennominae), included (9S,10R)-(Z,Z)-cis-9,10-epoxy-3,6-octadecadiene as a main sex pheromone component. The synthetic (9S,10R)-9,10-epoxydiene, rather than its antipode, elicited strong antennal and behavioral responses from the male moths in electrophysiological and field tests.     

Chiral discrimination in the exchange of α-tocopherol stereoisomers between plasma and red blood cells

The transport of 2R,4′R, 8′R-α-tocopherol and 2S,4′R,8′R-α-tocopherol from plasma into rat red blood cell membranes occurs with essentially no chiral discrimination. The previously demonstrated (10) preference of red blood cell membranes favoring 2R,4′R,8′R-α-tocopherol over the 2S,4′R, 8′R stereoisomer is shown to be due to better retention of the former compound, i.e., to preferential retention of natural vitamin E.     

Rational design, synthesis and pharmacological evaluation of the (2R)- and (2S)-stereoisomers of 3-(2-carboxypyrrolidinyl)-2-methyl acetic acid as ligands for the ionotropic glutamate receptors

In this paper we describe the rational design, synthesis and pharmacological evaluation of two new stereoisomeric (S)‐glutamate (Glu) analogues. The rational design was based on hybrid structures of the natural product kainic acid, a synthetic analogue CPAA and the high‐affinity Glu analogue SYM2081. Pharmacological evaluation of the two stereoisomers revealed that one stereoisomer showed a subtype selectivity profile with low micromolar affinity for GluK1 and GluK3 and a 10‐ to 15‐fold lower affinity for GluK2. The other stereoisomer displayed full selectivity for the KA over AMPA and NMDA receptors (GluK1–3: 0.39, 0.51 and 0.099 µM , respectively).     

Pheromone chirality of asian palm weevils,Rhynchophorus ferrugineus (Oliv.) andR. vulneratus (Panz.) (Coleoptera: Curculionidae)

Production of 4-methyl-5-nonanol, and 4-methyl-5-nonanone by two sympatric Asian palm weevils,Rhynchophorus ferrugineus (Oliv.) andR. vulneratus (Panz.) suggested that enantiospecificity of either compound could impart species specificity of pheromone communication. Weevil-produced, racemic 4-methyl-5-nonanol and 4-methyl-5-nonanone and their stereoselectively synthesized optical isomers were subjected to gas chromatographic-electroantennographic detection (GC-EAD) and GC-mass spectrometry (MS) on a chiral Cyclodex-B column. Only theS,S stereoisomer of 4-methyl-5-nonanol was EAD active and was produced by bothR. ferrugineus andR. vulneratus. Production and EAD activity of (S)-4-methyl-5-nonanone exceeded that of its antipode in both weevils. In field experiments in Java. (4S, 5S)-4-methyl-5-nonanol and the stereoisomeric mixture were equally attractive. The 4R,5R stereoisomer was inactive. The corresponding ketone enantiomers neither enhanced nor reduced attraction to (4S,5S)-4-methyl-5-nonanol. Lack of apparent differences betweenR. ferrugineus andR. vulneratus pheromones suggests that synonomy of both weevils should be considered unless other pre- or postzygotic reproductive isolating mechanisms are disclosed in future studies.     

The Absolute Configuration of Chrysomelidial: A Widely Distributed Defensive Component Among Oribotririid Mites (Acari: Oribatida)

The absolute configuration of the iridoid monoterpene chrysomelidial from the oribatid mite, Austrotritia dentate Aoki, was elucidated by the GC-MS and GC comparisons with four synthetic stereoisomers of this well-known natural product. This identification was made possible by asymmetric synthesis of the known alcohol, (5S,8S)-chrysomelidiol. The GC retention time of diol derived from the natural oribatid dial agreed with that of the synthetic (5S,8S)-chrysomelidiol, confirming that the absolute configurations at C5 and C8 positions of the natural chrysomelidial are both S. Chrysomelidial was detected as a single or a major component in nine oribatid mites examined; thus, this compound is considered to be commonly distributed in Oribotririidae where it serves a defensive role.     

Preparation of 8-methyl-2-decanol: General synthesis of diastereomeric mixtures of alkyl branched insect pheromones

A general method for synthesis of insect pheromones having alkyl branched carbon skeletons is demonstrated with the preparation of a diastereomeric mixture of 8-methyl-2-decanol, whose propionate is an attractant of someDiabrotica species. The procedure involves reaction of a ketone with lithium acetylide ethylenediamine complex to afford a propargylic alcohol containing the branch of the target molecule. Copper (1) mediated alkylation of the derived propargylic acetate with a primary alkyl halide yields a trisubstituted allene having the desired chain length, and isomerization with an alkali metal amide of either ethylenediamine or 1,3-diaminopropane, affords the alkyl branched terminal acetylene. The triple bond is converted to the methyl ketone and reduced to the methyl carbinol. The reactions proceed in good yield, and can be conveniently carried out on large scale. The method should prove useful for production of pheromone components in cases where diastereomeric mixtures can be employed.Issued as NRCC No. 27519.     

Iron-catalyzed reaction products of α-tocopherol with methyl 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoate

α-Tocopherol was reacted with methyl 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoate in the presence of an iron-chelate, Fe(III)-acetylacetonate, at 37°C in benzene. The reaction was carried out either aerobically or anaerobically. The main products of α-tocopherol under air were isolated and identified as two stereoisomers of 4a,5-epoxy-8a-hydroperoxy-α-tocopherone, four stereoisomers of methyl 9-(8a-dioxy-α-tocopherone)-12,13-epoxy-10(E)-octadecenoate, four stereoisomers of methyl 11-(8a-dioxy-α-tocopherone)-12,13-epoxy-9(Z)-octadecenoate, two stereoisomers of methyl 13(S)-(8a-dioxy-α-tocopherone)-9(Z),11(E)-octadecadinoate, and α-tocopherol dimer. Besides the 8a-(lipid-peroxy)-α-tocopherones, two stereoisomers of methyl 11-(α-tocopheroxy)-12(S),13(S)-epoxy-9(E)-octadecenoate, two stereoisomers of methyl 9-(α-tocopheroxy)-12(S),13(S)-epoxy-10(E)-octadecenoate, and two isomers of methyl (α-tocopheroxy)-octadecadienoate were obtained under nitrogen atmosphere. The results indicate that the peroxyl radicals from lipid hydroperoxides prefer to react with the 8a-carbon radical of α-tocopherol and the carbon-centered radicals react with the phenoxyl radical of α-tocopherol.     

Bis‐(1,2,3,4‐tetrahydroisoquinolinium): A Chiral Scaffold for Developing High‐Affinity Ligands for SK Channels

N‐Methyl‐bis‐(1,2,3,4‐tetrahydroisoquinolinium) analogues derived from AG525 (1,1′‐(propane‐1,3‐diyl)‐bis‐(6,7‐dimethoxy‐2‐methyl‐1,2,3,4‐tetrahydroisoquinoline)) stereoisomers and tetrandrine, a rigid bis‐(1,2,3,4‐tetrahydroisoquinoline) analogue with an S,S configuration, were synthesized and tested for their affinity for small‐conductance calcium‐activated potassium channel (SK/K_Ca2) subtypes using radioligand binding assays. A significant increase in affinity was observed for the quaternized analogues over the parent 1,2,3,4‐tetrahydroisoquinoline compounds. Interestingly, the impact of stereochemistry was not the same in the two groups of compounds. For quaternized analogues, affinities of S,S and R,R isomers for SK2 and SK3 channels were similar and in both cases higher than that of the meso derivative. Among the bis‐tetrahydroisoquinoline compounds, the S,S isomers exhibited high affinity, while the R,R and meso isomers had similarly lower affinities. Furthermore, the SK2/SK3 selectivity ratio was slightly increased for quaternized analogues. Bis‐(1,2,3,4‐tetrahydroisoquinolinium) represents a new scaffold for the development of high‐affinity ligands for SK channel subtypes.