RESUMEN
Polyene cyclization of compounds 3 and 4 under catalysis with AlCl3 and/or SnCl4 gave rise to complex bicyclic products 8 and 9, structures of which were highly unexpected, and X-ray analyses were invoked for unambiguously structural identification. Mechanistically, a tandem sigma-bond rearrangement process, including an unusual through-space 1,5-hydride or 1,3-alkyl shift as a key operation, is proposed.
Asunto(s)
Alquenos/química , Cetonas/química , Catálisis , Cinamatos/química , Ciclización , Estructura Molecular , Estereoisomerismo , Zinc/químicaRESUMEN
An operationally simple and high-yielding procedure has been developed for the conversion of primary amides to the corresponding nitriles, using ethyl dichlorophosphate/DBU as the mild dehydrating agent.
Asunto(s)
Amidas/química , Nitrilos/química , Estructura Molecular , Agua/químicaRESUMEN
A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.
Asunto(s)
Antivirales/síntesis química , Carbamatos/síntesis química , Cisteína Endopeptidasas/química , Dipéptidos/síntesis química , Proteínas Virales/antagonistas & inhibidores , Proteínas Virales/química , Animales , Antivirales/química , Antivirales/farmacología , Carbamatos/química , Carbamatos/farmacología , Línea Celular , Chlorocebus aethiops , Coronavirus Humano 229E/efectos de los fármacos , Proteasas 3C de Coronavirus , Cristalografía por Rayos X , Dipéptidos/química , Dipéptidos/farmacología , Estabilidad de Medicamentos , Humanos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Modelos Moleculares , Estructura Molecular , Ratas , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Relación Estructura-Actividad , Replicación Viral/efectos de los fármacosRESUMEN
Enone phosphonates 1 and 2 were found to be excellent dienophiles for the Diels-Alder reaction, giving phosphonate-containing polycycles, and the phosphonate group of the resulting adducts facilitated both the installation of an angular alkyl group via a reductive alkylation process and the regioselective generation of a ring junction double bond via an intramolecular Wadsworth-Horner-Emmons reaction.