RESUMEN
Novel quinazolin- and benzothiazol-6-yloxyacetamides show excellent in vivo activity against the three economically most important Oomycete pathogens Phytophthora infestans, Plasmopara viticola and Pythium ultimum. They are polar analogs of known quinolin-6-yloxyacetamides, which are not active against the soil-borne damping-off disease caused by Pythium ultimum. The Bogert quinazoline synthesis, an almost forgotten heterocyclization technique, proved to be highly useful for the concise construction of required quinazolin-6-ol building blocks.
Asunto(s)
Acetamidas/síntesis química , Acetamidas/farmacología , Benzotiazoles/síntesis química , Benzotiazoles/farmacología , Fungicidas Industriales/química , Fungicidas Industriales/farmacología , Oomicetos/efectos de los fármacos , Quinazolinas/síntesis química , Quinazolinas/farmacología , Acetamidas/química , Benzotiazoles/química , Relación Dosis-Respuesta a Droga , Fungicidas Industriales/síntesis química , Estructura Molecular , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Quinazolinas/química , Relación Estructura-ActividadRESUMEN
A novel class of experimental fungicides has been discovered, which consists of special quinolin-6-yloxyacetamides. They are highly active against important phytopathogens, such as Phytophthora infestans (potato and tomato late blight), Mycosphaerella graminicola (wheat leaf blotch) and Uncinula necator (grape powdery mildew). Their fungicidal activity is due to their ability to inhibit fungal tubulin polymerization, leading to microtubule destabilization. An efficient synthesis route has been worked out, which allows the diverse substitution of four identified key positions across the molecular scaffold.
Asunto(s)
Acetamidas/química , Antifúngicos/síntesis química , Moduladores de Tubulina/síntesis química , Acetamidas/síntesis química , Acetamidas/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Phytophthora infestans/efectos de los fármacos , Quinolinas/química , Saccharomycetales/efectos de los fármacos , Relación Estructura-Actividad , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologíaRESUMEN
An enantioselective synthesis of the antifungal natural product (+)-ambruticin S has been accomplished starting with the readily available methyl alpha-d-glucopyranoside, (R)-Roche ester, and (S)-glycidol as chirons, which encompassed seven of the 10 stereogenic centers of the target molecule. The remaining three centers were set by a highly diastereoselective, asymmetric cyclopropanation employing a chiral, nonracemic phosphonamide reagent. Our strategy for the construction of the dihydropyran subunit involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization. Other key steps in the synthesis featured an epoxide opening with a dithiane anion, two efficient phosphonamide-anion based olefinations, and a late-stage C-glycosylation.
Asunto(s)
Antifúngicos/síntesis química , Antifúngicos/química , Factores Biológicos/síntesis química , Factores Biológicos/química , Ciclización , Glicosilación , Conformación Molecular , Piranos/síntesis química , Piranos/química , EstereoisomerismoRESUMEN
A review, outlining the origins and subsequent development of the triketone class of herbicidal 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors.
Asunto(s)
4-Hidroxifenilpiruvato Dioxigenasa/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Herbicidas/química , Cetonas/química , 4-Hidroxifenilpiruvato Dioxigenasa/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Herbicidas/síntesis química , Herbicidas/farmacología , Cetonas/síntesis química , Cetonas/farmacología , Relación Estructura-ActividadRESUMEN
Alkynylalanes provide a new, copper-free route to skipped diynes when combined with propargylic electrophiles bearing an aluminum-complexing leaving group. The reaction is mild, efficient, and, in contrast to copper-mediated methods, highly regioselective. [reaction: see text]
RESUMEN
[reaction: see text] We have developed a novel reaction between a terminal TMS-alkyne and a propargyl halide in the presence of a fluoride source and a catalytic amount of copper iodide to prepare 1,4-skipped diynes with good yields and in mild conditions. We have shown that this reaction also works very well with germanium and tin derivatives as an alternative to silicon. This new method can be useful for the synthesis of polyunsaturated fatty acids.
RESUMEN
Thermodynamic and structural properties of a chemically modified DNA-RNA hybrid in which a phosphodiester linkage is replaced by a neutral amide-3 linkage (3'-CH(2)-CONH-5') were investigated using UV melting experiments, molecular dynamics simulations in explicit water, and continuum solvent models. van't Hoff analysis of the experimental UV melting curves suggests that the significant increase of the thermodynamic stability of a 15-mer DNA-RNA with seven alternated amide-3 modifications (+11 degrees C) is mainly due to an increased binding enthalpy. To further evaluate the origin in the observed affinities differences, the electrostatic contribution to the binding free energy was calculated by solving the Poisson-Boltzmann equation numerically. The nonelectrostatic contribution was estimated as the product of a hydrophobic surface tension coefficient and the surface area that is buried upon double strand formation. Structures were taken from 10 ns molecular dynamics simulations computed in a consistent fashion using explicit solvent, counterions, and the particle-mesh Ewald procedure. The present preliminary thermodynamic study suggests that the favorable binding free energy of the amide-3 DNA single strand to the complementary RNA is equally driven by electrostatic and nonpolar contributions to the binding compared to their natural analogues. In addition, molecular dynamics simulations in explicit water were performed on an amide-3 DNA single strand and the corresponding natural DNA. Results from the conformations cluster analysis of the simulated amide-3 DNA single strand ensembles suggest that the 25% of the population sampled within 10 ns has a pre-organized conformation where the sugar C3' endo pucker is favored at the 3'-flanking nucleotides. These structural and thermodynamic features contribute to the understanding of the observed increased affinities of the amide-3 DNA-RNA hybrids at the microscopic level.