RESUMO
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.
Assuntos
Alcenos/química , Cetonas/química , Catálise , Cinamatos/química , Ciclização , Estrutura Molecular , Estereoisomerismo , Zinco/químicaRESUMO
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.
Assuntos
Amidas/química , Nitrilas/química , Estrutura Molecular , Água/químicaRESUMO
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.
Assuntos
Antivirais/síntese química , Carbamatos/síntese química , Cisteína Endopeptidases/química , Dipeptídeos/síntese química , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/química , Animais , Antivirais/química , Antivirais/farmacologia , Carbamatos/química , Carbamatos/farmacologia , Linhagem Celular , Chlorocebus aethiops , Coronavirus Humano 229E/efeitos dos fármacos , Proteases 3C de Coronavírus , Cristalografia por Raios X , Dipeptídeos/química , Dipeptídeos/farmacologia , Estabilidade de Medicamentos , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Modelos Moleculares , Estrutura Molecular , Ratos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacosRESUMO
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.