RESUMEN
Novel 2-aryl-cyclic-1,3-diones containing a 5-methoxy-[1,2,5]triazepane unit were explored towards an effective and wheat safe control of grass weeds. Their preparation builds on the ease of synthetic access to 7-membered heterocyclic [1,2,5]triazepane building blocks. Substitution and pattern hopping in the phenyl moiety revealed structure-activity relationships in good agreement with previously disclosed observations amongst the pinoxaden family of acetyl-CoA carboxylase inhibitors. In light of basic physicochemical, enzyme inhibitory and binding site properties, the N-methoxy functionality effectively acts as a bioisostere of the ether group in the seven-membered hydrazine ring.
Asunto(s)
Acetil-CoA Carboxilasa/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Herbicidas/farmacología , Cetonas/farmacología , Acetil-CoA Carboxilasa/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Herbicidas/síntesis química , Herbicidas/química , Cetonas/síntesis química , Cetonas/química , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Postemergence control of grass weeds has become problematic due to the evolution of resistance to 5-enolpyruvylshikimate-3-phosphate synthase, acetyl-CoA carboxylase (ACCase), and acetolactate synthase-inhibiting herbicides. Herein we describe the invention and synthesis journey toward metproxybicyclone, the first commercial carbocyclic aryl-dione ACCase-inhibiting herbicide for the cost-effective management of grass weeds in dicotyledonous crops and in preplant burndown applications. Glasshouse and field experiments have shown that metproxybicyclone is safe for use on soybean, cotton, and sugar beet, among other crops. It is effective on a variety of key grass weeds including Eleusine indica, Digitaria insularis, Sorghum halepense, and Echinochloa crus-galli. Importantly, metproxybicyclone was more efficacious at killing resistant grass weed populations than current ACCase herbicides. Metproxybicyclone controlled the main ACCase target-site and nontarget site resistant mechanisms in characterized Lolium multiflorum and E. indica populations under glasshouse conditions. Excellent control of a broad resistance-causing D2078G target-site mutant E. indica population was also observed under field conditions.
Asunto(s)
Acetil-CoA Carboxilasa , Resistencia a los Herbicidas , Herbicidas , Malezas , Poaceae , Control de Malezas , Herbicidas/farmacología , Herbicidas/química , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/antagonistas & inhibidores , Acetil-CoA Carboxilasa/metabolismo , Malezas/efectos de los fármacos , Malezas/enzimología , Resistencia a los Herbicidas/genética , Poaceae/efectos de los fármacos , Poaceae/química , Poaceae/enzimología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/químicaRESUMEN
SmI2 has been used to cleave a sulfur linker and trigger cyclizations in strategies for the traceless fluorous synthesis of N-heterocycles. The studies give further insights into the reactivity of samarium enolates.
Asunto(s)
Flúor/química , Samario/química , CiclizaciónRESUMEN
A fluorous, cyclative-capture strategy based on a new Pummerer cyclization process allows rapid access to tagged, heterocyclic frameworks. Convenient modification of the fluorous, heterocyclic scaffolds by using a variety of approaches including Pd-catalyzed cross-couplings is possible. Traceless, reductive cleavage of the fluorous-phase tag or oxidative cleavage and further elaboration, completes a strategy for the high-throughput, fluorous-phase synthesis of a diverse range of N-heterocycles.