RESUMO
A reductive cyclization to prepare a variety of N-heterocycles, through the use of ortho-vinylanilides, is reported. The reaction is catalyzed by an inexpensive and bench-stable iron complex and generally occurs at ambient temperature. The transformation likely proceeds through hydromagnesiation of the vinyl group, and trapping of the inâ situ generated benzylic anion by an intramolecular electrophile to form the heterocycle. This iron-catalyzed strategy was shown to be broadly applicable and was utilized in the synthesis of substituted indoles, oxindoles and tetrahydrobenzoazepinoindolone derivatives. Mechanistic studies indicated that the reversibility of the hydride transfer step depends on the reactivity of the tethered electrophile. The synthetic utility of our approach was further demonstrated by the formal synthesis of a reported bioactive compound and a family of natural products.
RESUMO
A combination of electrospray-ionization mass spectrometry and Mössbauer spectroscopy was used to investigate the species generated in situ in highly enantioselective Fe/NHC-catalyzed C-H alkylations. The findings indicate an organometallic iron(ii)-NHC species to be of key relevance in the asymmetric catalysis.
RESUMO
Highly enantioselective nickel-catalyzed alkene endo-hydroarylations were accomplished with full selectivity by organometallic C-H activation. The asymmetric assembly of chiral six-membered scaffolds proved viable in the absence of pyrophoric organoaluminum reagents within an unprecedented nickel/JoSPOphos manifold.
RESUMO
The design and synthesis of macrocyclic inhibitors of human rhinovirus 3C protease is described. A macrocyclic linkage of the P1 and P3 residues, and the subsequent structure-based optimization of the macrocycle conformation and size led to the identification of a potent biochemical inhibitor 10 with sub-micromolar antiviral activity.
Assuntos
Antivirais/farmacologia , Inibidores de Cisteína Proteinase/farmacologia , Desenho de Fármacos , Compostos Macrocíclicos/farmacologia , Rhinovirus/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores , Proteases Virais 3C , Antivirais/síntese química , Antivirais/química , Cristalografia por Raios X , Cisteína Endopeptidases/metabolismo , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/química , Relação Dose-Resposta a Droga , Humanos , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/química , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Rhinovirus/enzimologia , Relação Estrutura-Atividade , Proteínas Virais/metabolismoRESUMO
Highly enantioselective iron-catalyzed C-H alkylations by inner-sphere C-H activation were accomplished with ample scope. High levels of enantiocontrol proved viable through a novel ligand design that exploits a remote meta-substitution on N-heterocyclic carbenes within a facile ligand-to-ligand H-transfer C-H cleavage.