RESUMEN
Pestalone (1) is a prominent marine natural product first isolated by M. Cueto et al. in 2001 from a co-fermentation of a marine fungus with a marine bacterium. For more than 10 years, 1 had been considered as a promising new antibiotic compound, the reported MIC against methicillin-resistant Staphylococcus aureus (MRSA) being 37 ng/mL. After overcoming the limited availability of 1 by total synthesis (N. Slavov et al., 2010) we performed new biological tests, which did not confirm the expected degree of antibiotic activity. The observed activity of pestalone against different MRSA strains was 3-10 µg/mL, as determined independently in two laboratories. A number of synthetic derivatives of 1 including pestalachloride A and other isoindolinones (formed from 1 by reaction with amines) did not exhibit higher activities as compared to 1 against MRSA and a series of plant pathogens.
Asunto(s)
Anisoles/farmacología , Antibacterianos/farmacología , Antifúngicos/farmacología , Benzofenonas/farmacología , Isoindoles/farmacología , Anisoles/química , Anisoles/aislamiento & purificación , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Benzofenonas/química , Benzofenonas/aislamiento & purificación , Resistencia a la Enfermedad , Isoindoles/química , Isoindoles/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
An easy access to 5-fluoropyridazines by a [2 + 1]/[3 + 2]-cycloaddition sequence between terminal alkynes, a difluorocarbene, and a diazo compound is reported. This approach does not necessitate the isolation of any intermediates, and a wide range of novel 5-fluoropyridazines was synthesized from readily available starting materials. Additionally, these compounds were used as a platform to access novel and highly diversified pyridazines.
Asunto(s)
Alquinos/química , Compuestos Azo/química , Hidrocarburos Fluorados/química , Piridazinas/síntesis química , Catálisis , Reacción de Cicloadición , Estructura Molecular , Piridazinas/químicaRESUMEN
A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H-phosphonates, H-phosphinates, and secondary phosphine oxides has been developed. This coupling reaction constitutes the first general method allowing the introduction of a great diversity of phosphorus substituents on the different carbons of the pyrazole ring in a one-step process.
Asunto(s)
Organofosfonatos/química , Compuestos Organofosforados/síntesis química , Paladio/química , Fosfinas/química , Pirazoles/síntesis química , Catálisis , Estructura Molecular , Compuestos Organofosforados/química , Pirazoles/químicaRESUMEN
Natural products play an important role as lead structures for the identification of novel active ingredients in crop protection. As it is the case in the pharmaceutical industry, however, many crop protection companies have substantially decreased their in-house efforts in natural product exploration. Therefore, joint projects with academic research groups become more and more important in the field. This review describes several examples for successful collaborations in the field of fungicidal natural products.