RESUMO
The axial-equatorial conformational isomer distribution of the reactant diazoacetoacetate or its metal carbene intermediate is reflected in Rh(II) catalyzed oxonium ylide forming reactions of 3-(trans-2-arylvinyl)tetrahydropyranone-5-diazoacetoacetates that afford diastereoisomeric products for both the symmetry-allowed [2,3]- and the formally symmetry-forbidden [1,2]-oxonium ylide rearrangements.
Assuntos
Acetoacetatos/química , Oniocompostos/química , Ródio/química , Catálise , Cristalografia por Raios X , Metano/análogos & derivados , Conformação Molecular , Estrutura Molecular , EstereoisomerismoRESUMO
Dirhodium catalyzed reactions of aryl-substituted tetrahydropyranone diazoacetoacetates produce ylide intermediates that unexpectedly yield two oxabicyclo[4.2.1]-nonane diastereoisomers, but a single diastereoisomer is formed by increasing the steric bulk of the aryl substituent.
Assuntos
Acetoacetatos/química , Compostos Bicíclicos com Pontes/química , Pironas/química , Ródio/química , Catálise , Modelos Moleculares , EstereoisomerismoRESUMO
The incidence of dengue fever epidemics has increased dramatically over the last few decades. However, no vaccine or antiviral therapies are available. Therefore, the need for safe and effective antiviral drugs has become imperative. The entry of dengue virus into a host cell is mediated by its major envelope (E) protein. The crystal structure of the E protein reveals a hydrophobic pocket that is presumably important for low-pH-mediated membrane fusion. High-throughput docking with this hydrophobic pocket was performed, and hits were evaluated in cell-based assays. Compound 6 was identified as one of the inhibitors and had an average 50% effective concentration of 119 nM against dengue virus serotype 2 in a human cell line. Mechanism-of-action studies demonstrated that compound 6 acts at an early stage during dengue virus infection. It arrests dengue virus in vesicles that colocalize with endocytosed dextran and inhibits NS3 expression. The inhibitors described in this report can serve as molecular probes for the study of the entry of flavivirus into host cells.
Assuntos
Antivirais/farmacologia , Vírus da Dengue/patogenicidade , Bibliotecas de Moléculas Pequenas , Internalização do Vírus/efeitos dos fármacos , Animais , Antivirais/química , Sítios de Ligação , Linhagem Celular , Cricetinae , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/crescimento & desenvolvimento , Humanos , Modelos Moleculares , Relação Estrutura-Atividade , Proteínas do Envelope Viral/antagonistas & inibidoresRESUMO
Heating of the solid ammonium salts obtained from treatment of mellitic acid with 3 equiv of a primary amine yields trisubstituted mellitic triimides via dehydration and imide ring closure. This surprisingly simple synthetic approach is amenable to incorporation of alkyl, aryl, and amino acid ester substituents, thereby opening broad access to a family of C(3)-symmetric organic electron acceptors.
