RESUMEN
A significant reason for developing innovative insecticidal active agents is the exponential rise in resistance to traditional chemical pesticides. Exploring new classes of insecticidal compounds with distinct mechanisms of action is one way to address this difficulty. So that, novel aryl thioamides derivatives 3-15 has been synthesized viaone-pot, three-component reaction of aroyl chloride, ammonium thiocyanate, and aromatic amines in dry acetone. The newly synthesized compounds' structures were validated by various spectroscopic methods, including elemental analysis, 1H-NMR, 13C NMR, and infrared spectroscopy. Under laboratory circumstances, the synthesized compounds showed good and broad-spectrum insecticidal activities toward S. littorali. When compared to other synthetic target compounds, 2,4-dichloro-N-[(3-fluorophenyl)carbamothioyl]benzamide 11, 2,4-dichloro-N-[(3-fluorophenyl)carbamothioyl]benzenecarbothioamide 13 showed good insecticidal activity, with 46.33â mg/L and LC50 values of 49.25â mg/L for 2nd instar larvae. Furthermore, the compound 3 was the least toxic in controlling the second and fourth instar larvae of S. littoralis on tomato leaves. Additionally, several histopathological and biochemical features of the some synthesized compounds under laboratory circumstances were also examined.
Asunto(s)
Diseño de Fármacos , Insecticidas , Spodoptera , Tioamidas , Animales , Insecticidas/farmacología , Insecticidas/síntesis química , Insecticidas/química , Spodoptera/efectos de los fármacos , Relación Estructura-Actividad , Tioamidas/química , Tioamidas/farmacología , Tioamidas/síntesis química , Larva/efectos de los fármacos , Estructura Molecular , Hormonas Juveniles/farmacología , Hormonas Juveniles/química , Hormonas Juveniles/síntesis química , Relación Dosis-Respuesta a DrogaRESUMEN
Ecdysone receptor (EcR) and chitinase play a critical role in the molting stage of insect pests. Each of them is considered a promising target for the development of novel insect growth regulators (IGRs). In the present paper, a total of 24 (23 novel) hexacyclic pyrazolamide derivatives were designed and synthesized by reducing the heptacycle and inserting small flexible linkers on the basis of the previously discovered dual-target compound D-27 acting simultaneously on EcR and Ostrinia furnacalis chitinase (OfChtI). Their insecticidal activities against Plutella xylostella, Spodoptera frugiperda, and Ostrinia furnacalis larvae were evaluated. The results revealed that the insecticidal activity was not significantly enhanced when the heptacycle on the pyrazole ring was reduced to a hexacycle. However, the insertion of an additional methylene spacer between the substituted phenyl ring and the amide bond can improve the insecticidal activity. Among the derivatives, the most potent compound, 6j, exhibited promising insecticidal activities against P. xylostella and S. frugiperda. Further protein binding assays and molecular docking indicated that 6j could target both EcR and OfChtI, and is a potential lead compound for IGRs. The present work provides valuable clues for the development of new dual-target IGRs.
Asunto(s)
Diseño de Fármacos , Insectos , Insecticidas , Hormonas Juveniles , Animales , Quitinasas/antagonistas & inhibidores , Insecticidas/síntesis química , Insecticidas/química , Insecticidas/farmacología , Hormonas Juveniles/síntesis química , Hormonas Juveniles/química , Hormonas Juveniles/farmacología , Simulación del Acoplamiento Molecular , Insectos/efectos de los fármacos , Insectos/crecimiento & desarrolloRESUMEN
Insect growth regulators (IGRs), which can interrupt or inhibit pest life cycles, are low-toxicity pesticides widely used in integrated pest management (IPM). Ecdysone analogues and chitinase inhibitors are familiar IGRs that have attracted considerable attention because of their unique modes of action and low toxicity to non-target organisms. To find new and highly effective candidate IGRs with novel mechanisms, D-08 (N-(4-(tert-butyl)phenyl)-2-phenyl-2,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-5-carboxamide) was chosen as a lead compound, and a series of novel heptacyclic pyrazolamide derivatives were designed and synthesized using the scaffold hopping strategy. The bioassay showed that III-27 (N-(2-methylphenethyl)-1-phenyl-1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-5-carboxamide) had excellent activity against Plutella xylostella. Protein verification and molecular docking indicated that III-27 could act on both the ecdysone receptor (EcR) and Ostrinia furnacalis chitinase (Of ChtI) and is a promising new lead IGRs. The interaction mechanism of III-27 with EcR and Of ChtI was then studied by molecular docking. These results provide important guidance for the study of new dual-target IGRs.
Asunto(s)
Amidas/farmacología , Descubrimiento de Drogas , Hormonas Juveniles/farmacología , Mariposas Nocturnas/efectos de los fármacos , Pirazoles/farmacología , Amidas/síntesis química , Amidas/química , Animales , Quitinasas/metabolismo , Relación Dosis-Respuesta a Droga , Hormonas Juveniles/síntesis química , Hormonas Juveniles/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Pirazoles/síntesis química , Pirazoles/química , Receptores de Esteroides/metabolismo , Relación Estructura-ActividadRESUMEN
Insect growth regulators (IGRs) can cause abnormal growth and development in insects, resulting in incomplete metamorphosis or even death of the larvae. Ecdysone receptor (EcR) and chitinase in insects play indispensable roles in the molting process. Ecdysone analogues and chitinase inhibitors are considered as potential IGRs. In order to find new and highly effective IGR candidates, based on the structure-activity relationship and molecular docking results of the active compound 6i (3-(tert-butyl)-N-(4-(tert-butyl)phenyl)-1-phenyl-1H-pyrazole-5-carboxamide) discovered in our previous work, we changed the t-butyl group on the pyrazole ring into heptacycle to enhance the hydrophobicity. Consequently, a series of novel heptacyclic pyrazolamide derivatives were designed and synthesized. The bioassay results demonstrated that some compounds showed obvious insecticidal activity. Especially, D-27 (N-(4-(tert-butyl)phenyl)-2-phenyl-2,4,5,6,7,8-hexahydrocyclohepta[c]pyrazole-5-carboxamide) showed good activities against Plutella xylostella (LC50, 51.50 mg·L-1) and Mythimna separata (100% mortality at 2.5 mg·L-1). Furthermore, protein validation indicated that D-27 acts not only on the EcR but also on chitinase Of ChtI. Molecular docking and molecular dynamics simulation explained the vital factors in the interaction between D-27 and receptors. D-27 may be a new lead candidate with a dual target in which Of ChtI shall be the main one. This work created a new starting point for discovering a novel type of IGRs.
Asunto(s)
Insecticidas/síntesis química , Insecticidas/farmacología , Hormonas Juveniles/síntesis química , Hormonas Juveniles/farmacología , Animales , Quitinasas/química , Quitinasas/metabolismo , Diseño de Fármacos , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Insecticidas/química , Hormonas Juveniles/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Mariposas Nocturnas/química , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/crecimiento & desarrollo , Mariposas Nocturnas/metabolismo , Receptores de Esteroides/química , Receptores de Esteroides/metabolismo , Relación Estructura-ActividadRESUMEN
A mixture of (E,Z)-isomers of methyl 12-trishomofarnesoate (methyl 3,7,11-trimethyl-2,6,10-pentadecatrienoate), a juvenile hormone mimic, was synthesized in nine steps (32.6% overall yield) by starting from only four commercially available materials: 2-hexanone, vinylmagnesium bromide, methyl acetoacetate and trimethyl phosphonoacetate. The mimic is useful in increasing the yield of silk by elongating the larval period of the silkworm, Bombyx mori (L.).
Asunto(s)
Ácidos Grasos Insaturados/síntesis química , Hormonas Juveniles/síntesis química , Seda/química , Animales , Bombyx/química , Larva/química , EstereoisomerismoRESUMEN
BACKGROUND: The FGLa-allatostatins (ASTs) are a family of neuropeptides that can inhibit juvenile hormone biosynthesis by the corpora allata (CA) in vitro, and therefore they are regarded as insect growth regulator (IGR) candidates for pest control. In our previous studies, an AST mimic, H17, was found to have a significant effect on JH biosynthesis by cockroach CA, both in vitro and in vivo. To discover new potential mimics and explore the substituent effect on the inhibition of JH biosynthesis, 30 analogues, modified with various substituents on the benzene ring at the N-terminus of lead compound H17, were designed and synthesised. Their bioactivity in inhibiting JH biosynthesis by the CA of Diploptera punctata and the potency of M9, M10 and M11 in activation of Dippu-AstR were evaluated. RESULTS: All the analogues showed an effect on JH biosynthesis by CA in vitro. M9, M10 and M11 can activate the Dippu-AstR, albeit with much lower potency than that of AST 1. M11 also exhibited improved in vitro activity (IC50 6.98 nm) in comparison with the lead compound H17 (IC50 29.5 nm). In particular, M11 displayed good in vivo activity in inhibiting JH biosynthesis and basal oocyte growth. CONCLUSION: The structure-activity relationship studies suggest that different positions of substituents on the benzene ring of the cinnamic acid can lead to different activities. The para-substitution on the benzene ring plays an important role in inhibiting JH biosynthesis in vitro. Moreover, M11 is considered to be a potential IGR for cockroach control. © 2016 Society of Chemical Industry.
Asunto(s)
Cucarachas/efectos de los fármacos , Hormonas Juveniles/farmacología , Neuropéptidos/farmacología , Animales , Corpora Allata/efectos de los fármacos , Corpora Allata/metabolismo , Femenino , Insecticidas/síntesis química , Insecticidas/farmacología , Hormonas Juveniles/síntesis química , Neuropéptidos/síntesis química , Relación Estructura-ActividadRESUMEN
A pair of chemical isomeric structures of novel N-tert-butylphenyl thenoylhydrazide compounds I and II were designed and synthesized. Their structures were characterized by MS, IR, (1)H NMR, elemental analysis and X-ray single crystal diffraction. The regioselectivity of the Meerwein arylation reaction and the electrophilic substitution reaction of N-tert-butyl hydrazine were studied by density functional theory (DFT) quantum chemical method. The larvicidal tests revealed that some compounds I had excellent larvicidal activity against Culex pipiens pallens. As the candidates of insect growth regulators (IGRs), the larval growth inhibition and regulation against Culex pipiens pallens were examined for some compounds, especially I1 and I7. Compounds I1 and I7 were further indicated as an ecdysteroid agonist by reporter gene assay on the Spodoptera frugiperda cell line (Sf9 cells). Finally, a molecular docking study of compound I7 was conducted, which was not only beneficial to understand the structure-activity relationship, but also useful for development of new IGRs for the control of mosquitos.
Asunto(s)
Hidrazinas/química , Insecticidas/química , Hormonas Juveniles/química , Larva/efectos de los fármacos , Animales , Culex/efectos de los fármacos , Culex/patogenicidad , Humanos , Hidrazinas/síntesis química , Hidrazinas/farmacología , Insecticidas/síntesis química , Insecticidas/farmacología , Hormonas Juveniles/síntesis química , Hormonas Juveniles/farmacología , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Spodoptera/efectos de los fármacos , Spodoptera/patogenicidad , Relación Estructura-ActividadRESUMEN
BACKGROUND: Diacyl hydrazines have attracted significant interest in medicine, pesticide chemistry and material science. It is an important class of insect growth regulators. In this study, acyl hydrazine, the essential active group was incorporated in to nalidixic acid with the aim of combining the active groups to generate more potent agrochemical. RESULTS: Various nalidixic acid based diacyl and sulphonyl acyl hydrazines derivatives were synthesized and characterized by spectral techniques. These compounds were screened for the antifungal activity against five pathogenic fungi, nitrification inhibitory activity and insect growth regulator (IGR) activity against Spodoptera litura. The fungicidal activity was screened against R. bataticola, S. rolfsii, R. solani, F. oxysporum and A. porri. Most of the compounds showed moderate to good antifungal activity against A. porri (ED50 = 29.6-495.9 µg/mL). All the compounds showed significant nitrification inhibitory activity at 5% level. IGR activity was examined by feeding method against S. litura. CONCLUSION: The study revealed that a few compounds possessed good activity against three different pests namely certain fungus, soil bacteria and insect, among which, compound 37 (R' = 4-chlorophenyl) behaved the best.
Asunto(s)
Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Fungicidas Industriales/farmacología , Hidrazinas/farmacología , Hormonas Juveniles/farmacología , Spodoptera/efectos de los fármacos , Animales , Antibacterianos/síntesis química , Fungicidas Industriales/síntesis química , Hidrazinas/síntesis química , Hormonas Juveniles/síntesis química , Larva/efectos de los fármacos , Nitrificación/efectos de los fármacos , Spodoptera/crecimiento & desarrolloRESUMEN
Insect-growth regulators (IGRs) have been receiving foremost attention as potential means of selective insect control. Benzoyl phenyl urea (BPU) is a well-known IGR having chitin synthesis inhibitor activity. Mimics of BPU have been synthesized by suitable derivatization of a naturally occurring monoterpenoid, thymol (2-isopropyl-5-methyl phenol) to form a = series of substituted benzoyl thymyl thioureas (BTTUs) [IVa-f] and benzoyl thymyl ureas (BTUs) [Va-f]. The synthesized compounds have been characterized by (1)H and (13)C NMR, LC-MS and elemental analysis. These derivatives have been screened for their effect on total haemocyte count of Dysdercus koenigii. It has been observed that the introduction of substituted benzoyl thiourea and urea linkage into a thymol ring via an amino group results in higher activity than the parent compound thymol and a comparable pattern of results with the standard insect-growth regulators, Penfluron. Urea [Va-f] compounds exhibited greater effect on Total Haemocyte Count (THC) than thiourea [IVa-f]. Fluoro substitution enhanced the effect on THC more than chloro substituted compounds, while ortho-substitution resulted in a better effect than para-substitution. The results described in this paper are promising and provide new array of synthetic chemicals that may be utilized as insect growth regulators.
Asunto(s)
Hemocitos/efectos de los fármacos , Hormonas Juveniles/análisis , Hormonas Juveniles/síntesis química , Tiourea/análisis , Animales , Heterópteros/efectos de los fármacos , Control de Insectos/métodos , Espectroscopía de Resonancia Magnética , Compuestos de Fenilurea/análisis , Compuestos de Fenilurea/síntesis química , Tiourea/análogos & derivados , Tiourea/síntesis químicaRESUMEN
Enormous numbers of synthetic fluorine-containing compounds have been widely used in a variety of fields, especially in drug and pesticide design. To find novel insect growth regulators, a series of benzoylphenylureas with fluorinated substituents were designed and synthesized. The results of larvicidal activities of those novel fluoro-substituted benzoylphenylureas against oriental armyworm and mosquito revealed that most compounds exhibited excellent activities. It is worth mentioning that compounds 3 and 6 exhibited higher activities against oriental armyworm and mosquito than commercial Hexaflumuron. It can be further seen that the insecticidal activities would increase significantly by introducing fluorinated substituents into the structure of the designed benzoylphenylureas.
Asunto(s)
Diseño de Fármacos , Insecticidas/síntesis química , Hormonas Juveniles/síntesis química , Compuestos de Fenilurea/síntesis química , Animales , Culex/efectos de los fármacos , Culex/crecimiento & desarrollo , Insecticidas/química , Insecticidas/farmacología , Hormonas Juveniles/química , Hormonas Juveniles/farmacología , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Estructura Molecular , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/crecimiento & desarrollo , Compuestos de Fenilurea/química , Compuestos de Fenilurea/farmacología , Relación Estructura-ActividadRESUMEN
Cockroach-type allatostatins (ASTs) were discovered in cockroaches through their capacity to inhibit the production of juvenile hormone by the corpora allata (CA). ASTs were considered as potential insect growth regulator (IGR) candidates, but several disadvantages, including the absence of the effect in vivo and rapid degradation in vivo, precluded their application in pest management. The CA were selected as the target, and the core pentapeptide region (YDFGL) was chosen as the lead sequence in the search for new IGRs based on the allatostatins. We designed and synthesized 24 analogues, which mimicked each amino acid of the core region, to determine structure-activity relationships and the possibility of shortening the ASTs in the core region while retaining activity. The results suggest that the sequence FGLa is more important than Y/FX because Y/FX mimics show strong effects in vitro and in vivo. In particular, compound I3 was synthesized by substitution of Y/FX with 6-phenylhexnoic acid and exhibits higher activity in vitro than the complete core region. Furthermore, compound I3 has a clear effect in vivo on juvenile hormone (JH) biosynthesis of Diploptera punctata females, providing a possible application for cockroach management. On the basis of the structure-activity relationship of pentapeptide analogues, a general structure of potential potent AST analogues is proposed here. A new approach using peptidomimetics in the discovery of IGRs is demonstrated in our study.
Asunto(s)
Hormonas Juveniles/química , Hormonas Juveniles/farmacología , Neuropéptidos/química , Neuropéptidos/farmacología , Oligopéptidos/química , Oligopéptidos/farmacología , Peptidomiméticos/química , Secuencia de Aminoácidos , Animales , Cucarachas/efectos de los fármacos , Cucarachas/fisiología , Femenino , Hormonas Juveniles/síntesis química , Masculino , Datos de Secuencia Molecular , Estructura Molecular , Neuropéptidos/síntesis química , Relación Estructura-ActividadRESUMEN
A series of 10 new pro-juvenoids (juvenogens, insect hormonogenic compounds, pro-drug-like agents) was synthesized using isomeric synthetic juvenoids (insect juvenile hormone analogs) and steroid molecules as patterns modifying parts of the complex hormonogenic molecules. In addition, several new synthons were prepared, which were required by the designed synthetic protocol to achieve the target molecules. These pro-juvenoids were subjected to the topical screening tests and to the drinking assays on the red firebug (Pyrrhocoris apterus), a convenient model laboratory phytophagous insect. Simple and efficient synthetic procedures for the preparation of the target pro-juvenoids and their synthons are presented. Furthermore, the biological activity of the pro-juvenoids in comparison with the activity of their parent juvenoids and that of several commercially available agents is demonstrated. Juvenoids and pro-juvenoids may replace toxic insecticides persistent in the insect pest control because they have no adverse effects on non-target organisms and/or human.
Asunto(s)
Hormonas Juveniles/síntesis química , Esteroides/química , Animales , Heterópteros/efectos de los fármacos , Control de Insectos , Hormonas Juveniles/química , Hormonas Juveniles/farmacología , Relación Estructura-ActividadRESUMEN
Metabolites of the 6,7,10,11 bisepoxide juvenile hormone III (JHB(3)), and other potential juvenoids, were tested for juvenile hormone activity using early instar or early stage pupae of Drosophila melanogaster. Importantly, methyl farnesoates were tested as they might have JH-like activity on Dipteran juveniles. Larvae were exposed to compounds in medium, or the compounds were applied to white puparia. In the assays employed in the present study, there was no indication for JH activity associated with the metabolites of JHB(3). The activity of methyl farnesoate (MF) was higher than that of JH III and far greater than bisepoxide JH III. As opposed to the two endogenous juvenile hormones, methyl farnesoate has weak activity in the white puparial bioassay. When fluorinated forms of methyl farnesoate, which is unlikely to be converted to JH, were applied to Drosophila medium to which fly eggs were introduced, there was a high degree of larval mortality, but no evidence of subsequent mortality at the pupal stage. One possible explanation for the results is that methyl farnesoate is active as a hormone in larval stages, but has little activity at the pupal stage where only juvenile hormone has a major effect.
Asunto(s)
Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/crecimiento & desarrollo , Ácidos Grasos Insaturados/farmacología , Hormonas Juveniles/farmacología , Animales , Bioensayo , Ácidos Grasos Insaturados/síntesis química , Hormonas Juveniles/síntesis química , Pupa/efectos de los fármacosRESUMEN
The development of new types of environmentally safe insecticides has been advantageous to replace toxic and persistent insecticides, which have adverse effects on animals and humans. Our effort in this field was aimed at the synthesis of insect juvenile hormone analogues, juvenoids, nontoxic for warm-blooded animals and fish, which can become advanced compounds in regulating many aspects in insect physiology. Structure modification of juvenoids via juvenogen derivatives (hormonogenic substances) plays an important role in controlling the juvenoid liberation rate in the insect digestive system and can also play an important role in the mode of action toward different arthropod groups, with focus on insect pest species. For that reason, juvenoids were esterified with hexadecanoic, butanoic, and 3-methylbut-2-enoic acids. A total of 12 new compounds with potential insecticidal activity were synthesized and characterized, and the results of biological screening tests on blowflies Neobellieria (Sarcophaga) bullata were presented. Results of the inhibitory activity of the tested compounds on the reproduction of the blowflies were also presented.
Asunto(s)
Dípteros , Insecticidas/síntesis química , Hormonas Juveniles/síntesis química , Animales , Dípteros/fisiología , Esterificación , Femenino , Insecticidas/química , Hormonas Juveniles/química , Hormonas Juveniles/farmacología , Espectroscopía de Resonancia Magnética , Ovario/efectos de los fármacos , Ovario/ultraestructura , Reproducción/efectos de los fármacosRESUMEN
Insect growth regulators play an important role in Integrated Pest Management systems. Cockroach-type allatostatins (FGLamides) (ASTs), which are a family of basic peptides first isolated from brains of Diploptera punctata were originally discovered on the basis of their ability to inhibit the production of juvenile hormone by the corpora allata. For this reason, the ASTs can be regarded as possible IGR candidates for pest control although the absence of effect in vivo, rapid degradation and high production costs of the natural peptides preclude their use in pest management. However, we have synthesized a new AST mimic, H17, from the pentapeptide C-terminal active core of the AST. This mimic is able to significantly inhibit the biosynthesis of JH by cockroach CA in vitro (IC(50) value: 12 nM) and in vivo following injection (IC(50) value: 33 nM). H17 also shows a highly significant inhibition of JH production in topical cuticular assays in vivo. Our results suggest that H17 has potential as an IGR for cockroach control.
Asunto(s)
Cucarachas , Hormonas Juveniles/síntesis química , Hormonas Juveniles/farmacología , Neuropéptidos/química , Péptidos/síntesis química , Péptidos/farmacología , Animales , Cucarachas/efectos de los fármacos , Cucarachas/fisiología , Femenino , Hormonas Juveniles/química , Estructura Molecular , Neuropéptidos/farmacología , Oocitos/efectos de los fármacos , Oviposición/efectos de los fármacos , Péptidos/químicaRESUMEN
Steroidal compounds have been utilized as carriers and for modification of physico-chemical properties of model biologically active secondary alcohols - juvenoids. Juvenoids are juvenile hormone analogues - environmentally safe insecticides, possessing significant biological activity towards different arthropods groups in focus on insect pest species. Structure modification of juvenoids plays important role to control the rate of liberation and decomposition of juvenoid in digestive system and can also play important role in the mode of action towards selected insect. This study presents an approach to the synthesis of steroidal monomers and dimers carrying one and two molecules of a juvenoid in their structures. The prepared compounds were tested for their inhibition activity on reproduction of the blowfly Neobellieria (Sarcophaga) bullata. These steroid-juvenoid conjugates showed promising possibilities in synthesis of new unique biochemical insecticides. Preliminary biological test results of prepared compounds are presented.
Asunto(s)
Ácido Cólico/química , Hormonas Juveniles/síntesis química , Hormonas Juveniles/farmacología , Plaguicidas/síntesis química , Plaguicidas/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Dimerización , Dípteros/citología , Dípteros/efectos de los fármacos , Dípteros/crecimiento & desarrollo , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Femenino , Hormonas Juveniles/química , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Masculino , Plaguicidas/química , Reproducción/efectos de los fármacosRESUMEN
Ageratochromes or precocenes are known for their insect growth regulating (IGR) activity. The present investigation was taken up with an objective to look for the lead structure in these compounds which can be elaborated synthetically to obtain useful growth regulators for practical purposes. With this in mind, some variants of precocenes were synthesized in the laboratory and tested for their toxicity and growth regulating activity using red cotton bug Dysdercus koenigii as the test insect. Most of the precocenoids showed toxicity of various degree and metamorphic derangements to different extents. Adults emerging from treated nymphs could not complete the normal life span. Among the compounds tested 8-acetyl-7-hydroxy-5-methoxy-dimethylchromene (alloevodinol) was more toxic and also showed developmental defects at very low dose such as 0.5 mg l(-1)/nymph. Precocene II (6, 7-dimethoxy-2, 2-dimethylchromene) was used as the standard compound. It was the least toxic and showed effects at 30 mg l(-1)/nymph.
Asunto(s)
Benzopiranos/síntesis química , Heterópteros/efectos de los fármacos , Control de Insectos , Hormonas Juveniles/síntesis química , Animales , Benzopiranos/química , Benzopiranos/toxicidad , Heterópteros/crecimiento & desarrollo , Hormonas Juveniles/química , Hormonas Juveniles/toxicidad , Dosificación Letal Mediana , Ninfa/efectos de los fármacos , Ninfa/crecimiento & desarrolloRESUMEN
During the investigation of ester derivatives (juvenogens, biochemically activated insect hormonogenic compounds) of biologically active alcohols with potential application in insect pest control, a need for availability of all existing stereoisomers of ethyl N-{2-[4-(2-butanoyloxycyclohexyl)methyl]phenoxy}ethyl carbamate occurred. They were synthesized from their chiral precursors, the corresponding stereoisomers of 2-(4-methoxybenzyl)cyclohexyl butanoate, by removing their protecting group (methyl), and by subsequent condensation of the aromatic hydroxyl moiety with ethyl N-(2-bromoethyl) carbamate. The requested enantiomers of 2-(4-methoxybenzyl)cyclohexyl butanoate were obtained by a Candida antarctica lipase-mediated transesterification and chiral resolution of the respective racemic cis- and trans-isomers of 2-(4-methoxybenzyl)cyclohexanol either directly or after a subsequent chemical esterification of the chiral precursor. In this synthesis, two convenient butanoic acid activating esters, vinyl butanoate and 2,2,2-trifluoroethyl butanoate, were employed, and the chiral precursors in the synthesis of the target molecules were obtained in 41-48% yields (i.e., 82-96% conversion), and with enantiomeric purity ee=96-98%, respectively. The enantiomeric purity of the products was determined by chiral HPLC analysis, and their absolute configuration was assigned on the basis of analyzing the (1)H and (19)F NMR spectra of their diastereoisomeric Mosher acid (3,3,3-trifluoromethyl-2-methoxy-2-phenylpropanoic acid) esters.
Asunto(s)
Butiratos/farmacología , Ésteres/farmacología , Insectos , Insecticidas/farmacología , Hormonas Juveniles/farmacología , Control de Plagas , Animales , Butiratos/química , Esterificación , Ésteres/síntesis química , Ésteres/química , Control de Insectos , Insecticidas/síntesis química , Insecticidas/química , Hormonas Juveniles/síntesis química , Hormonas Juveniles/química , Lipasa/metabolismo , Estructura Molecular , EstereoisomerismoRESUMEN
We report an improved method for the synthesis of high specific activity insect [10-(3)H]juvenile hormones (JH) I, II, and III which affords both enantiomers of each in high optical purity. A synthetic route for JH I was modified to give higher yields and purity. We increased the specific activity of the synthetic [10-(3)H]JHs using normal phase liquid chromatography optimized to give near baseline resolution of [10-(3)H]JHs and unlabeled JHs. Racemic [10-(3)H]JHs and their corresponding diol metabolites were enantiomerically separated using a chiral column eluted with 2-propanol:hexane. Acidic hydration of the unnatural antipode of the [10-(3)H]JHs gives the diol antipode with the same stereochemistry as that from epoxide hydrolase action on the natural JH antipode. The [10-(3)H]JH diol enantiomers can also be resolved with the same chiral column using a more polar solvent. The synthesis of high specific activity chiral ethyl ester analogs of JH I and II can also be accomplished using this synthetic route.
Asunto(s)
Hormonas Juveniles/síntesis química , Animales , Clorhidrinas/química , Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada , Marcaje Isotópico/métodos , Hormonas Juveniles/análisis , Hormonas Juveniles/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Manduca , Espectrometría de Masas , Conteo por Cintilación , Espectrofotometría Ultravioleta , Estereoisomerismo , TritioRESUMEN
A series of 8 new juvenogens (3--10) was prepared starting from a pair of isomeric insect juvenile hormone bioanalogues ( and ). The biological activity of the juvenogens -- was tested for their effect on reproduction of the blowfly Neobellieria (Sarcophaga) bullata and for the juvenilizing activity on the termite Prorhinotermes simplex. Results of biological screening are important in structure--activity studies and promising for potential practical application of some of the juvenogens studied, especially against termites.