[Insecticidal action of synthetic girgensohnine analogues and essential oils on Rhodnius prolixus (Hemiptera: Reduviidae)].

INTRODUCTION: The alkaloid girgensohnine has been used as a natural model in the synthesis of new alkaloid-like alpha-aminonitriles with insecticidal effect against disease vectors. OBJECTIVE: To evaluate the biocide activity of girgensohnine analogues and essential oils of Cymbopogon flexuosus, Citrus sinensis and Eucalyptus citriodora in stage I and stage V Rhodnius prolixus nymphs. MATERIALS AND METHODS: We used a topical application model in tergites and sternites, as well as exposure to treated surfaces with different exploratory doses of each of the molecules and essential oils to determine the lethal doses (LD50 and LD95). RESULTS: Analogue 3 showed the highest insecticidal activity with 83.3±16.7% of mortality when applied on tergites, 38.9±4.8% on sternites and 16.7±0% on treated surfaces in stage I nymphs at 72 hours (h) and 500 mg.L-1. In stage V nymphs, the compounds induced mortality only in sternums (11.1±9.6% for analogue 6 and 5.5±4.7% for analogues 3 and 7 at 72 h and 1500 mg.L-1). The lethal doses for molecule 3 on tergites in stage I nymphs were LD50 225.60 mg.L-1 and LD95 955.90 mg.L-1. The insecticidal effect of essential oils was observed only in stage I nymphs, with 11.1±4.8% for C. flexuosus when applied in sternites, while using exposure to surfaces treated it was 5.6±4.8% for C. sinensis applied on tergites and 8.3±0% on sternites at 72 h and 1000 mg.L-1. CONCLUSION: Synthetic girgensohnine analogues, and C. flexuosus and C. sinensis essential oils showed insecticidal activity in R. prolixus. Analogue 3 showed the greatest insecticidal activity among all molecules and oils evaluated under our laboratory conditions.

Insecticidal action of synthetic girgensohnine analogues and essential oils on Rhodnius prolixus (Hemiptera: Reduviidae) / Acción insecticida de análogos sintéticos de girgensohnina y de aceites esenciales sobre Rhodnius prolixus (Hemiptera: Reduviidae)

ABSTRACT Introduction: The alkaloid girgensohnine has been used as a natural model in the synthesis of new alkaloid-like alpha-aminonitriles with insecticidal effect against disease vectors. Objective: To evaluate the biocide activity of girgensohnine analogues and essential oils of Cymbopogon flexuosus, Citrus sinensis and Eucalyptus citriodora in stage I and stage V Rhodnius prolixus nymphs. Materials and methods: We used a topical application model in tergites and sternites, as well as exposure to treated surfaces with different exploratory doses of each of the molecules and essential oils to determine the lethal doses (LD50 and LD95). Results: Analogue 3 showed the highest insecticidal activity with 83.3±16.7% of mortality when applied on tergites, 38.9±4.8% on sternites and 16.7±0% on treated surfaces in stage I nymphs at 72 hours (h) and 500 mg.L-1. In stage V nymphs, the compounds induced mortality only in sternums (11.1±9.6% for analogue 6 and 5.5±4.7% for analogues 3 and 7 at 72 h and 1500 mg.L-1). The lethal doses for molecule 3 on tergites in stage I nymphs were LD50 225.60 mg.L-1 and LD95 955.90 mg.L-1. The insecticidal effect of essential oils was observed only in stage I nymphs, with 11.1±4.8% for C. flexuosus when applied in sternites, while using exposure to surfaces treated it was 5.6±4.8% for C. sinensis applied on tergites and 8.3±0% on sternites at 72 h and 1000 mg.L-1. Conclusion: Synthetic girgensohnine analogues, and C. flexuosus and C. sinensis essential oils showed insecticidal activity in R. prolixus. Analogue 3 showed the greatest insecticidal activity among all molecules and oils evaluated under our laboratory conditions.

RESUMEN Introducción. El alcaloide natural girgensohnina se ha usado como modelo en la síntesis de nuevos análogos de alcaloidales alfa-aminonitrílicos con efecto insecticida en vectores de enfermedades. Objetivo. Evaluar la actividad biocida de análogos de girgensohnina y de aceites esenciales de las plantas Cymbopogon flexuosus, Citrus sinensis y Eucalyptus citriodora en ninfas de estadios I y V de Rhodnius prolixus. Materiales y métodos. Se empleó la aplicación tópica en terguitos, esternitos y superficies tratadas con diferentes dosis exploratorias de cada una de las moléculas y aceites esenciales para determinar las dosis letales (LD50 y LD95). Resultados. El análogo 3 tuvo la mayor actividad insecticida, con una mortalidad de 83,3±16,7% en los terguitos, de 38,9±4,8 % en los esternitos y de 16,7±0 % a las 72 horas en ninfas de estadioI expuestas a superficies tratadas y 500 mg.L-1. En las ninfas de estadio V solo se presentó mortalidad en los esternitos (11,1±9,6 % con el análogo 6 y 5,5±4,7 % con los análogos 3 y 7 a las 72 h y 1.500 mg.L-1). Las dosis letales para la molécula 3 en los terguitos de ninfas de estadio I fueron las siguientes: DL50, 225,60 mg.L-1 y DL95, 955,90 mg.L-1. En cuanto a los aceites esenciales, el efecto insecticida solo se presentó con C. flexuosus (11,1±4,8%) en los esternitos de ninfas de estadio I expuestas a superficies tratadas; con C. sinensis (5,6±4,8%) en los terguitos y en los esternitos (8,3±0%) a las 72 horas y 1.000 mg.L-1. Conclusión. Los análogos sintéticos del alcaloide girgensohnina y los aceites esenciales de C. flexuosus y C. sinensis exhibieron actividad insecticida en R. prolixus. El análogo 3 exhibió la mayor actividad insecticida de todas las moléculas evaluadas bajo las condiciones de laboratorio.

Synthesis of Enantiomeric Polyhydroxyalkylpyrrolidines from 1,3-Dipolar Cycloadducts. Evaluation as Inhibitors of a ß-Galactofuranosidase.

Enantiomeric 2,3,4-tris(hydroxyalkyl)-5-phenylpyrrolidines have been synthesized from the major cycloadducts obtained by the 1,3-dipolar cycloaddition of sugar enones with azomethine ylides derived from natural amino acids. Reduction of the ketone carbonyl group of the cycloadducts, which possess a basic structure of bicyclic 6-(menthyloxy)hexahydropyrano[4,3-c]pyrrol-7(6H)one, afforded a number of pyrrolidine-based bicyclic systems. A sequence of reactions, which involved hydrolysis of the menthyloxy substituent, reduction, N-protection, and degradative oxidation, afforded varied pyrrolidine structures having diverse configurations and patterns of substitution; in particular, polyhydroxylated derivatives have been obtained. The unprotected products were isolated as pyrrolidinium trifluoroacetates. Because of the furanose-like nature of the target trihydroxyalkyl pyrrolidines, these molecules have been evaluated as inhibitors of the ß-galactofuranosidase from Penicillium fellutanum. The compounds showed practically no inhibitory activity for concentration of pyrrolidines in the range of 0.1-1.6 mM.

Design, synthesis, acetylcholinesterase inhibition and larvicidal activity of girgensohnine analogs on Aedes aegypti, vector of dengue fever.

Girgensohnine alkaloid was used as a natural model in the design and generation of new alkaloid-like α-aminonitrile series that was completed by the use of SSA-catalyzed Strecker reaction between commercial and inexpensive substituted benzaldehydes, piperidine (pyrrolidine, morpholine and N-methylpiperazine) and acetone cyanohydrin. Calculated ADMETox parameters of the designed analogs revealed their good pharmacokinetic profiles indicating lipophilic characteristics. In vitro AChE enzyme test showed that obtained α-aminonitriles could be considered as AChEIs with micromolar IC50 values ranging from 42.0 to 478.0 µM (10.3-124.0 µg/mL). Among this series, the best AChE inhibitor was the pyrrolidine α-aminonitrile 3 (IC50 = 42 µM), followed by the piperidine α-aminonitriles 2 and 6 (IC50 = 45 µM and IC50 = 51 µM, respectively), and the compound 7 (IC50 = 51 µM). In vivo insecticidal activity of more active AChEIs against Aedes aegypti larvae was also performed showing a good larvicidal activity at concentrations less than 140 ppm, highlighting products 2 and 7 that could serve as lead compounds to develop new potent and selective insecticides.

1,3-Dipolar cycloaddition reactions of azomethine ylides with a cellulose-derived chiral enone. A novel route for organocatalysts development.

Cellulose-derived chiral pyrrolidines were synthesized in excellent yields, regioselectivities, and stereoselectivities via a 1,3-dipolar cycloaddition reaction between levoglucosenone and azomethine ylides. An unprecedented isomerization event led to a new family of pyrrolidines with an unusual relative stereochemistry. Preliminary results showed that these compounds are promising organocatalysts for iminium ion-based asymmetric Diels-Alder reactions.

Synthesis, properties and photodynamic inactivation of Escherichia coli by novel cationic fullerene C60 derivatives.

A novel N,N-dimethyl-2-(4'-N,N,N-trimethylaminophenyl)fulleropyrrolidinium iodide (DTC(60)(2+)) has been synthesized by 1,3-dipolar cycloaddition using 4-(N,N-dimethylamino) benzaldehyde, N-methylglycine and fullerene C(60). This approach produced an N-methyl-2-(4'-N,N-dimethylaminophenyl)fulleropyrrolidine with 38% yield. Exhaustive methylation of this fullerene derivative with methyl iodide yielded 95% of dicationic DTC(60)(2+). The spectroscopic and photodynamic properties of the DTC(60)(2+) were compared with a non-charged N-methyl-2-(4'-acetamidophenyl)fulleropyrrolidine (MAC(60)) and a monocationic N,N-dimethyl-2-(4'-acetamidophenyl)fulleropyrrolidinium iodide (DAC(60)(+)). The dicationic DTC(60)(2+) is essentially aggregated in solution of different solvents and it is partially dissolved as monomer in benzene/benzyl-n-hexadecyldimethyl ammonium chloride (BHDC) 0.1M/water (W(0)=10) reverse micelles. The singlet molecular oxygen, O(2) ((1)Delta(g)), production was evaluated using 1,3-diphenylisobenzofuran. The photodynamic effect was strongly dependent on the medium, diminishes when the sensitizer is aggregated and increases in an appropriately surrounded microenvironment. The photodynamic inactivation produced by these fullerene derivatives was investigated in vitro on a typical Gram-negative bacterium, Escherichia coli. Photosensitized inactivation of E. coli cellular suspensions by DTC(60)(2+) exhibits a approximately 3.5 log decrease of cell survival (99.97% of cellular inactivation), when the cultures are treated with 1 microM of sensitizer and irradiated for 30 min. This photosensitized inactivation remains high even after one washing step. Also, the photodynamic activity was confirmed by growth delay of E. coli cultures. The growth was arrested when E. coli was exposed to 2 microM of cationic fullerene and irradiated, whereas a negligible effect was found for the non-charged MAC(60). These studies indicate that dicationic DTC(60)(2+) is an interesting agent with potential applications in photodynamic inactivation of bacteria.

Isolation and synthesis of (-)-(5S)-2-imino-1-methylpyrrolidine-5- carboxylic acid from Cliona tenuis: structure revision of pyrostatins.

[reaction: see text] (-)-(5S)-2-Imino-1-methylpyrrolidine-5-carboxylic acid (1), previously reported as the N-acetyl-beta-d-glucosaminidase inhibitor pyrostatin B, has been isolated from the organic extracts of the burrowing sponge Cliona tenuis. The structure of 1, including its absolute stereochemistry, was characterized from its spectral data and chemical transformations and confirmed by total synthesis. The synthesis of 1 reveals that the structure of pyrostatin B has been incorrectly assigned. Comparison of NMR spectral data strongly suggests that pyrostatins A and B are identical to 5-hydroxyectoine and ectoine, respectively.

Total synthesis and identification of two diastereoisomers of 1-methyl-2-[N-(p-tolylsulfonyl)-2-pyrrolidinyl]ethyl beta-L-fucopyranoside.

The reaction of a racemic mixture of (2R,2'S)- and (2S,2'R)-N-(p-tolylsulfonyl)-2-pyrrolidinyl-2-propanol, prepared from (S)-proline, with 2,3,4-tri-O-acetyl-alpha-L-fucopyranosyl trichloroacetimidate led to both diastereoisomers of the title compound after O-deacetylation.

Heck arylation of endocyclic enecarbamates with diazonium salts. Improvements and a concise enantioselective synthesis of (-)-codonopsinine.

Total enantioselective synthesis of the natural (-)-codonopsinine was accomplished in seven steps with an overall yield of approximately 16% starting from the five-membered endocyclic enecarbamate 4. The total synthesis features a highly efficient and stereoselective Heck arylation of endocyclic enecarbamate 4 with p-methoxybenzenediazonium tetrafluoroborate and a stereoselective epoxidation/epoxide opening sequence as key steps.