A convenient synthesis of (2R,8R)-8-methyl-2-decanol and its 2S epimer,the parent alcohols of rootworm pheromones

A highly stereospecific synthesis of the title compound (2R,8R)-8-methyl-2-decanol (I) has been devised via 16 simple steps. The required chirons (5 and 11) were prepared from easily accessible templates viz. (R)-methyl citronel-late and (S)-glutamic acid. This on Grignard coupling furnished the ketal (12) which was converted to the desired epoxide (14) and subsequently reduced to furnish the alcohol (2R,8R)-I. Its corresponding (2S)-epimer was prepared by total stereoselective inversion of its C-2 center. The title compounds are the parent alcohols of the pheromone components of the female rootworms.     

Enantioselective synthesis of (R)- and (S)-2-methyl-[3,3,2-2H3] alanines

The synthesis of optically pure (R)- and (S)-2-methyl-[3,3,3-2H3] alanines of biological interest is described. The stereochemistry of the reaction of the lithio derivative of (R)-(-)-2,5-dimethoxy-3-benzyl-3-methyl-3,6-dihydropyrazine with alkyl and deuterated alkyl iodides is discussed. The configuration of the newly formed center of chirality in (R)- and (S)-2-methyl-[3,3,3-2H3] alanines is derived from 1H NMR.     

A study ofTyrophagus putrescentiae (Acari: Acaridae) as a facultative predator of southern corn rootworm eggs

An acarid mite,Tyrophagus putrescentiae (Schrank), was found to feed on southern corn rootworm (SCR) eggs in peanut and corn agroecosystems. In laboratory studies,T. putrescentiae eggs were generally oviposited directly on SCR eggs, and immatures fed only on previously damaged SCR eggs, depending upon adults to penetrate the chorion of SCR eggs. Individual adultT. putrescentiae significantly reduced (P<0.05) the number of larvae to eclose from 40 SCR eggs. Initial population levels of 1, 2, 5, 10, and 20 adult mites reduced the SCR egg population by 19, 43, 69, 92, and 98% respectively. Mites were attracted to SCR eggs from a distance of 8 cm, with significantly (P<0.001, ² test) more mites found in containers which included SCR eggs as compared with containers without SCR eggs. In greenhouse experiments, significantly (P<0.05) fewer SCR adults emerged from soil-filled containers which included 25T. putrescentiae and 100 SCR eggs, as compared with containers which had only SCR eggs. We suggest thatT.putrescentiae may be an important biological control agent of the SCR in certain agroecosystems.     

Synthesis of (1R,7Z)-1-methyl-7-hexadecenyl acetate, the female sex pheromone of the honey locust gall midge

(1R,7Z)-1-Methyl-7-hexadecenyl acetate (1), the female sex pheromone of the honey locust gall midge (Dasineura gleditchiae), was synthesized from 6-hepten-1-ol in an 8.9% overall yield (eight steps). Hydrolytic kinetic resolution of (±)-1,2-epoxy-8-heptadecyne was the key step in the synthesis.     

(2R,3S)-(+)- and (2S,3R)-(-)-Halofuginone lactate: synthesis, absolute configuration, and activity against Cryptosporidium parvum

The trans-enantiomers of the commercially important anti-protozoal compound Halofuginone have been prepared and characterized, and the absolute configuration was assigned by X-ray crystallography. The activity of both enantiomers against Cryptosporidium parvum was determined in vitro and related to acute toxicity in vivo. It was shown that both the activity and the toxicity are properties of the (2R,3S)-enantiomer. We conclude that with respect to broadening the therapeutic window there is no advantage in application of one enantiomer over the application of the racemic mixture in the treatment of C. parvum infections.     

Toxicity of Chromobacterium subtsugae to southern green stink bug (Heteroptera: Pentatomidae) and corn rootworm (Coleoptera: Chrysomelidae)

Diabrotica spp. (Coleoptera: Chrysomelidae) beetles and southern green stink bugs, Nezara viridula (L.) (Heteroptera: Pentatomidae), are pests on corn, Zea mays L., and soybean, Glycine max (L.) Merr., as well as on cucurbits. Control of these insects has depended on chemicals. An alternative to chemical control is the use of biologicals. Use of bacteria, fungi, viruses, pheromones, and metabolites to control these insects can potentially improve resistance management and reduce pesticide use. Other than Bacillus thuringiensis Berliner, few bacteria have been discovered that are lethal to either of these pests. Chromobacterium subtsugae Martin et al., a newly described bacterium that is known to be toxic to Colorado potato beetle, Leptinotarsa decemlineata (Say), larvae, was found to be toxic to both diabroticite adult beetles and southern green stink bug adults. In laboratory assays, toxins produced by these bacteria kill 80-100% of the adults of two species of diabroticite beetles, Diabrotica undecimpunctata howardi Barber and Diabrotica virgifera virgifera LeConte, and 100% of southern green stink bug adults within 6 d. For green stink bug, live bacteria were not needed for toxicity.     

Biomimetic conversion of (3S)-(-)-neodictyoprolenol to optically pure (1S,2R)-(-)-dictyopterene B,marine algal sex pheromone

Both enantiomers of (3S)-(-)- and (3R)-(+)-Neodictyoprolenol [(3S,5Z,8Z)-(-)-1,5,8-undecatrien-3-ol] were successfully converted to the algal sex pheromone, (1S,2R)-(-)-dictyopterene B and (1R,2S)-(+)-dictyopterene B in high enantiomeric purities (e. e. > 99%), respectively, by the biomimetic reaction involving phosphorylation and elimination under a mild condition.     

Soil moisture, no-tillage and predator effects on southern corn rootworm survival in peanut agroecosystems

Experiments examined the effects of no-tillage (NT) and conventional-tillage (CT) and increased soil moisture (irrigation) on southern corn rootworm (SCR), Diabrotica undecimpunctata howardi Barber (Coleoptera: Chrysomelidae), oviposition and survival and SCR below-ground predators in peanut (Arachis hypogeae L.) agroecosystems. No-tillage systems without irrigation had significantly greater soil moisture than CT systems without irrigation in 1987, but not in 1988. Both moist soil and the presence of an organic residue increased the number of southern corn rootworm eggs in a system. The same 17 species of predatory arthropods were found in all systems. However, their activity in the top 10-cm of soil which increased in NT systems, determined how effective they were as predators. Only 7 predators significantly reduced SCR immature stages, and of these 7, only one, Formicidae, preyed on all stages of SCR. Southern corn rootworm first instars and eggs had the greatest overall percent mortality, with second and third instars the lowest. Peanut yields and pod quality were equal between NT and CT systems. Overall return per ha showed NT, no-irrigation systems with the greatest return. Abiotic parameters dominated SCR survival in CT systems, while biotic parameters had the greatest influence on SCR survival in NT systems.

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Résumé Des expériences ont été entreprises pour examiner l'influence de labours classiques ou de leur absence et de l'augmentation de l'humidité du sol (irrigation) sur la ponte et la survie de D. undecimpunctata howardi Barber (Coleo. Chrysomelidae) et sur ses prédateurs souterrains dans des agrosystèmes à arachide. L'humidité du sol s'est montrée significativement plus élevée dans les parcelles irriguées pendant les deux années, 1987 et 1988, mais, en 1987 et non en 1988, l'humidité du sol a été significativement plus élevée dans le sol non labouré pourtant non irrigué que dans le sol labouré et irrigué. La présence de sol humide et de résidus organiques augmente le nombre d'ufs émis. Les mêmes 17 espèces d'arthropodes prédateurs dateurs souterrains ont été rencontrés dans toutes les sols non labourés et parfois dans les sols labourés irrigués; leur activité détermine leur efficacité comme prédateur. 7 espèces réduisent les effectifs de larves, mais une seule d'entre elles, une Formicidae, (Lasius spp. et Pheidole spp.) s'est révélée prédatrice de tous les stades de la chrysomèle. La plus forte mortalité de D. u. howardi a été observée sur les ufs et les larves de premier stade, la plus faible sur les larves de deuxième et troisième stade. La récolte et la qualité des arachides sont identiques avec ou sans labour. Ainsi, la rentabilité financière par ha était supérieure dans les systèmes sans labour non irrigués. Il découle de cette étude que les paramètres physiques dominent la survie de la chrysomèle dans les systèmes avec labour, tandis que les paramètres biologiques influent le plus sur la survie dans les systèmes sans labour.

     

Structure and formation of the peritrophic membrane in the larva of the southern corn rootworm, Diabrotica undecimpunctata

The peritrophic membrane (PM) in larvae of the southern corn rootworm Diabrotica undecimpunctata (Coleoptera:Chrysomelidae) forms along the full length of the midgut epithelium, defining D. undecimpunctata as a Type I insect with respect to PM formation. PM formation occurs in three phases: organization of a continuous lamella of matrix from material secreted into the interstices between the microvilli, maturation and apical movement of the lamella along the microvilli, and shedding of the lamella from the tips of the microvilli into the midgut lumen. Subsequent cycles of synthesis and shedding give rise to multiple, concentric lamellae which surround the food in the gut lumen. PM lamellae are 0.2 mum in profile width and consist of a core of bundles of 5 nm-diameter microfibers encased in a finely-granular homogeneous material. The microfiber bundles are arranged in an orthogonal grid-like array with dimensions consistent with formation around the microvilli. The homogeneous material separates from the PM lamellae to enclose food particles suggesting it may contain digestive enzymes. The PM, microvilli and intracellular vesicles in the midgut epithelium stain intensely with wheat germ agglutinin reflecting the presence and sites of secretion and synthesis of chitin.     

Determination of the enantiomeric composition of (R*,S*)-1-ethylpropyl 2-methyl-3-hydroxypentanoate, the male-produced aggregation pheromone of Sitophilus granarius

The enantiomeric composition of sitophilate, the granary weevil [Sitophilus granarius (L.)] male-produced aggregation pheromone [(R^*,S^*)-1-ethylpropyl 2-methyl-3-hydroxypentanoate)], was determined by three methods: (1) bioassaying the synthetic (2S,3R) and (2R,3S) enantiomers of the active (R^*,S^*) diastereomer; (2) ¹H NMR spectroscopy of Mosher ester derivatives of the natural pheromone and synthetic (2S,3R)-and (2R,3S)-sitophilate; and (3) capillary GLC comparisons of the retention times of derivatized natural pheromone and the two synthetic enantiomers. The combined methods confirmed the (2S,3R) enantiomer as the active form of sitophilate. Male granary weevils were shown to produce >96% (2S,3R)-sitophilate. No significant attraction of S. granarius by the (2R,3S) enantiomer was observed. Rice and maize weevils [S. oryzae (L.) and S. zeamais Motschulsky] were not attracted by (2S,3R)-sitophilate. S. granarius L. est un déprédateur important des grains stockés. Le (R^*,S^*)-1-éthylpropyl 2-méthyl-3-hydroxypentanoate a été identifié en 1987 comme le principal composé du sitophilate, la phéromone mâle d'agrégation de S. granarius. La composition énantiométrique du sitophilate a été déterminée par 3 méthodes:

Enantioselective synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine and their racemization-free incorporation into oligopeptides via solid-phase synthesis

An efficient method for the enantioselective synthesis of (2R, 3S)- and (2S, 3R)-4,4,4-trifluoro-N-Fmoc-O-tert-butyl-threonine on multigram scales was developed. Absolute configurations of the two stereoisomers were ascertained by X-ray crystallography. Racemization-free coupling conditions for the incorporation of tfT into oligopeptides were then explored. For solution-phase synthesis, tfT racemization was not an issue under conventional coupling conditions. For solid-phase synthesis, the following conditions were identified to achieve racemization-free synthesis: if tfT (3.0 equiv) was not the first amino acid to be linked to the resin (1.0 equiv), the condition is 2.7 equiv DIC/3.0 equiv HOBt as the coupling reagent at 0 degrees C for 20 h; if tfT (3.0 equiv) was the first amino acid to be linked to the resin (1.0 equiv), then 1.0 equiv of CuCl(2) needs to be added to the coupling reagent.     

Laccase-mediated synthesis of 2-methoxy-3-methyl-5-(alkylamino)- and 3-methyl-2,5-bis(alkylamino)-[1,4]-benzoquinones

The synthesis of 5-alkylamino- and 2,5-bis(alkylamino)-[1,4]-benzoquinones, showing structural similarity to natural mitomycins, was performed through coupling of 2-methoxy-3-methylhydroquinone with primary amines such as n-octylamine, geranylamine and cyclooctylamine using laccases from Myceliophthora thermophila (MtL) and Pycnoporus cinnabarinus SBUG-M 1044 (PcL). Product spectra of laccase reactions differ due to reaction systems pH values (pH 7.0 for MtL and pH 5.0 for PcL) applied to assure enzymes optimal catalytic efficiency. The MtL- and PcL-mediated formation of monoaminated products was achieved at equimolar reactant concentrations with amine coupling at the meta-position to benzoquinones methyl group. Increased formation of diaminated products occurred in PcL-mediated reactions and generally when the amine was supplied in excess. Diamination entailed elimination of the benzoquinone methoxy group (amination in para-position to the first amine substituent). Six products were synthesised and characterised by NMR and HR-MS analysis. The laccase-mediated amine coupling to 2-methoxy-3-methylhydroquinone confers two of the essential pharmaceutical active motifs from mitomycins: (i) a stable 1,4-benzoquinoic parent structure and (ii) a biological active alkylation function (NH).     

Western corn rootworm (Diabrotica virgifera virgifera LeConte) population dynamics

1 The western corn rootworm Diabrotica virgifera virgifera LeConte is a major insect pest of field maize, Zea mays L. Larvae can cause substantial injury by feeding on maize roots. Larval feeding may destroy individual roots or root nodes, and reduce plant growth, stability, and yield. Costs associated with managing corn rootworms in continuous maize are annually one of the largest expenditures for insect management in the United States Corn Belt.
2 Even though D. virgifera virgifera has been studied intensively for over 50 years, there is renewed interest in the biology, ecology, and genetics of this species because of its ability to rapidly adapt to management tactics, and its aggressive invasive nature.
3 This article provides a comprehensive review of D. virgifera virgifera population dynamics, specifically: diapause, larval and adult development, seasonality, spatial and temporal dynamics at local and landscape scales, invasiveness in North America and Europe, and non-trophic interactions with other arthropods.
4 Gaps in current knowledge are identified and discussed especially within the context of challenges that scientists in North America and Europe are currently facing regarding pest dynamics and the need to develop appropriate management strategies for each geographic area.     

Modeling the dynamics of adaptation to transgenic corn by western corn rootworm (Coleoptera: Chrysomelidae)

A simulation model of the population dynamics and genetics of the western corn rootworm, Diabrotica virgifera virgifera LeConte, was created for a landscape of corn, soybean, and other crops. Although the model was created to study a 2-locus problem for beetles having genes for resistance to both crop rotation and transgenic corn, during this first phase of the project, the model was simulated to evaluate only resistance management plans for transgenic corn. Allele expression in the rootworm and toxin dose in the corn plant were the two most important factors affecting resistance development. A dominant resistance allele allowed quick evolution of resistance to transgenic corn, whereas a recessive allele delayed resistance >99 yr. With high dosages of toxin and additive expression, the time required to reach 3% resistance allele frequency ranged from 13 to >99 yr. With additive expression, lower dosages permitted the resistant allele frequency to reach 3% in 2-9 yr with refuges occupying 5-30% of the land. The results were sensitive to delays in emergence by susceptible adults and configuration of the refuge (row strips versus blocks).     

Investigating the effectiveness of feeding deterrents against the southern corn rootworm, using behavioral bioassays and toxicity testing

Leaf-disk feeding tests were conducted to determine the effect of various chemicals on southern corn rootworm, Diabrotica undecimpunctata howardi Barber, larval feeding. Ethanolic extracts of plant seeds from the family Meliaceae were all highly active feeding deterrents, while hexane extracts were ineffective as deterrents. In leaf disk feeding tests, the fungicide thiram (tetramethylthiuram disulfide), as technical material or formulated as thiram 50% or 75% (AI) was also an effective feeding deterrent. In choice tests, all thiram-based deterrents were equally effective, while in no-choice tests, thiram-75 was most effective at preventing feeding. Thiram-75 was also effective in protecting corn seedlings in a soil bioassay mimicking the field environment. It was determined that the formulation of thiram-75 used in these tests had been contaminated with 0.87% dieldrin (by weight). The contaminated thiram-75 had a toxic action, as well as a deterrent effect on southern corn rootworm larvae and both factors contributed to overall feeding inhibition. Toxicity was not found in technical thiram or in thiram-50. The mode(s) of action of the various deterrents are discussed in relation to screening procedures.

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Resumé Des expériences de consommation avec et sans choix ont été utilisées pour déterminer l'effet de différentes substances sur la prise de nourriture par D. undecimpunctata howardi Barber. Des disques de feuilles de Zea mays avec dissuadants ont été présentés à des chenilles du troisième stade; l'état des disques a été examiné au bout de 3,6 et 24 h dans les expériences de choix et de 48 et 72 h en absence de choix.Les extraits éthanoliques (1% dans l'éthanol) de Méliacées sont tous très efficaces, tandis que ceux à l'hexane (1% dans le pentane) sont inefficaces. Le thiram (disulfure de tétraméthylethiuram) utilisé comme matériel technique, à 50% ou à 75%, est lui aussi efficace (à 0,5% ou 1% dans l'acétone). Lorsqu'il y a choix tous les thirams sont aussi dissuasifs, alors qu'en absence de choix le thiram 75% paraît le plus efficace. Lorsque ce dernier est contaminé par 0,87% en poids de dieldrine, il est efficace lors d'expériences simulant le sol du champ. La contamination par la dieldrine rend le thiram 75 toxique autant que dissuadant. Cette toxicité n'est pas observée sur le thiram technique ou le thiram 50. Les modes d'action des différents dissuadants sont discutés.

     

Synthesis of (3R,10R)- and (3S,10S)-Diastereomers of 3,10-Dimethylspermine

Russian Journal of Bioorganic Chemistry - A simple and practical 10-step synthesis is reported for previously unknown diastereomers of C?methylated spermine (Spm) analogue,...     

Synthesis of (2S,2'R,3S,4R)-2-(2'-hydroxy-21'-methyidocosanoylamino)-1,3,4-pentadecanetriol,the ceramide sex pheromone of the female hair crab,Erimacrus isenbeckii

The ceramide sex pheromone [(2S,2'R,3S,4R)-2-(2'-hydroxy-21-methyldocosanoylamino)-1,3,4-pentadecanetriol (1)] of the female hair crab (Erimacrus isenbeckii) was synthesized by starting from (S)-serine and 12-bromo-1-dodecanol.     

Discovery of (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide,a potent and orally efficacious mGlu5 receptor negative allosteric modulator

A novel series of selective negative allosteric modulators (NAMs) for metabotropic glutamate receptor 5 (mGlu5) was discovered from an isothiazole scaffold. One compound of this series, (1R,2R)-N-(4-(6-isopropylpyridin-2-yl)-3-(2-methyl-2H-indazol-5-yl)isothiazol-5-yl)-2-methylcyclopropanecarboxamide (24), demonstrated satisfactory pharmacokinetic properties and, following oral dosing in rats, produced dose-dependent and long-lasting mGlu5 receptor occupancy. Consistent with the hypothesis that blockade of mGlu5 receptors will produce analgesic effects in mammals, compound 24 produced a dose-dependent reduction in paw licking responses in the formalin model of persistent pain.     

Selective inhibition of thrombin by (2R,4R)-4-methyl-1-[N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl++ +) sulfonyl]-l-arginyl)]-2-piperidinecarboxylic acid

The potency of thrombin inhibition by 4-methyl-1-[N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)-sulfony l]- L-arginyl]-2-piperidinecarboxylic acid (MQPA) depended on the stereoconformation of the 2-piperidinecarboxylic acid moiety. Ki values for bovine alpha-thrombin were 0.019 microM with (2R,4R)-MQPA, 0.24 microM with (2R,4S)-MQPA, 1.9 microM with (2S,4R)-MQPA, and 280 microM with (2S,4S)-MQPA. (2R,4R)-MQPA of the four stereoisomers of MQPA was also the most potent inhibitor for other trypsin-like serine proteases with Ki values of 5.0 microM for trypsin, 210 microM for factor Xa, 800 microM for plasmin, and 1500 microM for plasma kallikrein. Examination of the potency of thrombin inhibition by arginine derivatives related to MQPA in structure suggested the presence of a specific binding site for the carboxamide portion (C-terminal side). The relative inhibitory potency of the four stereoisomers of MQPA for trypsin was nearly identical with that for thrombin, suggesting that the specific binding site for the carboxamide portion is present in both enzymes. Modification of thrombin by phosphopyridoxylation or the presence of heparin did not significantly alter the binding of MQPA.