RESUMO
This report describes an environmentally benign synthesis of 1,2,3-benzotriazines through an iodide-catalyzed electro-oxidative N-centered [1,2]-rearrangement of 3-aminoindazoles. The developed method demonstrates the activation of heteroatoms via electrochemically generated reactive iodide species without using any metal catalysts and peroxides. The protocol features practical and mild reaction conditions and displays a wide substrate scope. Various mechanistic experiments and cyclic voltammetric studies have been instrumental in elucidating the reaction mechanism, operating via a skeletal rearrangement of 3-aminoindazoles.
RESUMO
Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein, we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure-activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC50 values of 2.14 and 4.88 µM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, rendering this scaffold attractive for pursuing novel anti-influenza agents.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Animais , Cães , Humanos , Antivirais/uso terapêutico , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/tratamento farmacológico , Células Madin Darby de Rim CaninoRESUMO
A practical NaI/PPh3-catalyzed decarboxylative radical cascade cyclization of N-arylacrylamides with redox-active esters is described, which is mediated by visible light irradiation. A wide range of substrates bearing different substituents and derived from ubiquitous carboxylic acids, including α-amino acids, were synthesized and examined under this very mild, efficient, and cost effective transition-metal-free synthetic method. These afforded various functionalized oxindoles featuring a C3 quaternary stereogenic center. Mechanistic experiments suggest a radical mechanism.
RESUMO
An alkene sulfenoamination reaction with 2-aminothiophenol is developed using iodide catalysis. This reaction renders access to useful 1,4-benzothiazines with good functional group compatibility including both electron-donating and electron-withdrawing substituents. The reaction is proposed to proceed through an inversion of the polarity of the thiol functionality. Our mechanistic studies reveal that both thiiranium and thiyl radical pathways are plausible and that the disulfide reagent can also function as a viable substrate in this reaction.