RESUMEN
Rh-catalyzed direct C-H/C-H cross-coupling reaction of various (hetero)arenes with quinones is developed. This protocol is effective for a broad range of both quinone and arene substrates and a wide range of directing groups for this reaction, affording structurally diverse aryl-substituted quinones with high synthetic utility. Moreover, the present synthetic route allowed for the rapid construction of the carbazole quinone moiety that was identified as a new inhibitor scaffold for GSKß.
Asunto(s)
Carbazoles/química , Descubrimiento de Drogas , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Hidrocarburos Aromáticos/química , Quinonas/química , Quinonas/farmacología , Rodio/química , Adenosina Trifosfato/metabolismo , Catálisis , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Glucógeno Sintasa Quinasa 3/química , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Simulación del Acoplamiento Molecular , Quinonas/metabolismoRESUMEN
An efficient and practical method for effecting a tandem C-H alkenylation/C-O cyclization has been achieved via the C-H functionalization of flavone derivatives. The synthetic utility of the one-pot sequence was demonstrated by obtaining convenient access to coumarin-annelated benzopyrans. The reaction scope for the transformation was found to be fairly broad, affording good yields of a wide range of flavone- or coumarin-fused benzopyran motifs, which are privileged structures in many biologically active compounds.
RESUMEN
Concise and selective: the title one-pot sequence allows formation of the enone functionality and subsequent cross-coupling. The process provides access to highly functionalized cyclic enolones and enaminones from readily accessible ß-heteroatom-substituted cyclic ketones.
Asunto(s)
Cetonas/química , Paladio/química , Catálisis , Cromonas/química , Hidrogenación , Estructura Molecular , Acoplamiento Oxidativo , Quinolonas/químicaRESUMEN
Wrightiadione contains a unique tetracyclic isoflavone moiety and has been shown to exhibit a broad range of biological activities. An efficient and straightforward synthetic method for generating the molecular complexity of wrightiadione was developed through three-step tandem dehydrogenation/oxidation/oxidative cyclization reactions with a Pd/Cu catalytic system. This unprecedented one-pot route utilizes a broad range of substrates, providing a convenient and powerful synthetic tool for accessing naturally occurring tetracyclic isoflavone wrightiadione and its nitrogen-containing derivatives.
Asunto(s)
Apocynaceae/química , Isoflavonas/síntesis química , Catálisis , Ciclización , Isoflavonas/química , Estructura Molecular , Nitrógeno/química , Oxidación-Reducción , Corteza de la Planta/química , TailandiaRESUMEN
Frutinoneâ A, a biologically active ingredient of an antimicrobial herbal extract, demonstrates potent inhibitory activity towards the CYP1A2 enzyme. A three-step total synthesis of frutinoneâ A with an overall yield of 44 % is presented. The construction of the chromone-annelated coumarin core was achieved through palladium-catalyzed CH carbonylation of 2-phenolchromones. The straightforward synthetic route allowed facile substitutions around the frutinoneâ A core and thus rapid exploration of the structure-activity relationship (SAR) profile of the derivatives. The inhibitory activity of the synthesized frutinoneâ A derivatives were determined for CYP1A2, and ten compounds exhibited one-to-two digit nanomolar inhibitory activity towards the CYP1A2 enzyme.
Asunto(s)
Cromonas/síntesis química , Cumarinas/síntesis química , Paladio/química , Sitios de Unión , Catálisis , Cromonas/química , Cumarinas/química , Citocromo P-450 CYP1A2/química , Citocromo P-450 CYP1A2/metabolismo , Estructura Molecular , Conformación ProteicaRESUMEN
The one-pot dehydrogenation and ortho-functionalization sequence provides access to highly functionalized arylamine-containing derivatives from readily accessible cyclic N-acetyl enamides.
Asunto(s)
Amidas/química , Aminas/síntesis química , Paladio/química , Aminas/química , Catálisis , Hidrogenación , Estructura MolecularRESUMEN
An efficient method to effect C-O cyclization was developed via the C-H functionalization of chromones and coumarins, affording heterocyclic-fused benzofurans.
Asunto(s)
Benzofuranos/síntesis química , Cumarinas/química , Flavonas/química , Benzofuranos/química , CiclizaciónRESUMEN
A straightforward and efficient method for the palladium-catalyzed direct cross-coupling of chromones with various quinones has been developed to rapidly construct isoflavone quinone structural motifs.