RESUMEN
A cascade radical cyclization of alkenyl N-cyanamides with aromatic aldehydes has been achieved for an expeditious synthesis of keto-methylated dihydropyrrolo-quinazolinones. Benzoyl radicals, generated from aryl aldehydes in the presence of di-tert-butyl peroxide (DTBP), promoted the domino annulations leading to distinctive functionalized quinazolinones in good yields. In addition, the robustness of the present protocol is validated by employing heterocyclic and natural product-based aldehydes.
RESUMEN
Herein, we present the electrochemical synthesis of selenylated azaspiro[4.5]decadienones through domino selenylation/ipso-annulation of N-benzylacrylamides with diselenides. The method showed a wide substrate scope under mild and external oxidant-free reaction conditions, involving the construction of C-Se and C-C bonds. Gram-scale synthesis and further functional group conversion of the product are also demonstrated.
RESUMEN
The reaction of alkynyl p-quinone methide (pQM) with keto-methylenes through a base-mediated tandem 1,6-addition/annulation sequence, [2 + 3] annulation, affording the furans is reported for the first time. A variety of functionalized furans, including fused derivatives, were obtained in good to excellent yields under mild reaction conditions. The efficacy of alkynyl pQMs is highlighted by extending their use to access isoxazoles, pyrazoles via [3 + 2] annulation, and pyridines through [3 + 3] annulation in the presence of different bis-nucleophiles.
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An approach for the assembly of phenanthrone derivatives bearing all carbon quaternary centres has been developed through visible light-promoted tandem sulfonylation/intramolecular-arylation of biaryl enones with sulfonyl chlorides. A series of sulfonylated 10,10-dialkylphenanthrones were obtained in good yields. In addition, the approach has been extended to thiotrifluoromethyl (SCF3) and thiocyanato (SCN) radicals to obtain the corresponding phenanthrones under oxidative conditions. The synthetic utility was also illustrated by the scalability and further transformations of the product.
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A novel one-pot base-promoted insertion of indolyl 2-alkynes into a C-C single bond of 1,3-diketones, followed by intramolecular aldol reaction and dehydrative aromatization is described. This reaction cascade leads to the construction of 2-indolyl phenols involving the formation of the C1-C2 and C3-C4 bonds of phenols resulting from the formal insertion process with a good substrate scope. Further, these bifunctional compounds were used in a novel arylative annulation in the presence of Grignard reagents to provide chromeno-indole frameworks.
RESUMEN
Unprecedented domino aza-annulations of (E)-2-en-4-ynyl-acetonitriles (generated from the Morita-Baylis-Hillman acetates of propiolaldehydes for the first time) with sodium azide under metal- and oxidant-free conditions for the assembly of triazolo-pyridines are accomplished. The developed strategy offers broad substrate scope, extending to (2-alkynyl)aryl and indolyl-acetonitriles to provide the corresponding triazolo-fused isoquinolines and ß-carbolines, respectively, in good yields. Additionally, the synthetic utility of the products is demonstrated via denitrogenative coupling of fused triazoles with different nucleophiles.
RESUMEN
An unprecedented copper-catalyzed ipso-annulation reaction of N-(p-methoxyaryl)propiolamides with 1,3-diketones has been developed, which enables the assembly of diketoalkylated spiro[4.5]trienones involving oxidative dearomatization in the presence of ammonium persulfate [(NH4)2S2O8] as the oxidant. This protocol was extended to biaryl ynones, efficiently affording the diketoalkylated spiro[5.5]trienones in good yields. The significance of the diketoalkyl functionality has been illustrated by further transformation into 3-pyrazoyl spiro-trienone, a structurally unique motif.
Asunto(s)
Cobre , Compuestos de Espiro , Catálisis , Ciclización , Cetonas , Estrés OxidativoRESUMEN
An efficient selenylative cyclization of aryl-alkynones with diselenides in the presence of iron(III)chloride at room temperature to prepare 3-seleno-2-naphthols in good yields has been described. Furthermore, the resulting products were transformed into selenyl-naphthofuran and selenyl-1,2-naphthoquinone derivatives.
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Remdesivir, the first drug approved by the FDA to treat COVID-19, is in high demand for patients infected with the SARS-CoV-2 virus. Herein, we report a facile approach minimizing the protecting group manipulations to afford remdesivir in good overall yield.
RESUMEN
Electrooxidative-induced synthesis of structurally diverse seleno-dibenzocyclohepten-5-ones and seleno-spiro[5.5]trienones by selenylative carbannulation of biaryl ynones with diaryl diselenide has been developed. The switchable reactivity, intramolecular ortho-annulation or dearomative ipso-annulation, is directed by the substituent present on the ortho-aryl group of aryl-ynone. The prominent features of this method include metal-free, external chemical oxidant-free conditions, and readily accessible substrates.
Asunto(s)
Compuestos de Espiro , Estructura MolecularRESUMEN
A novel chemoselective [3 + 2] annulation reaction of easily accessible ketoxime acetate with 2-aryl-3-ethoxycarbonyl pyrroline-4,5-dione has been developed for the synthesis of unknown pyrrolo[2,3-b]pyrrole frameworks. This method involves copper-mediated N-O bond cleavage followed by the formation of carbon-carbon and carbon-nitrogen bonds. This operationally simple protocol provides broader functional group compatibility and good yields.
RESUMEN
We describe in this paper the synthesis of a novel series of anilino-2-quinazoline derivatives. These compounds have been screened against a panel of eight mammalian kinases and in parallel they were tested for cytotoxicity on a representative panel of seven cancer cell lines. One of them (DB18) has been found to be a very potent inhibitor of human "CDC2-like kinases" CLK1, CLK2 and CLK4, with IC50 values in the 10-30 nM range. Interestingly, this molecule is inactive at 100 µM on the closely related "dual-specificity tyrosine-regulated kinase 1A" (DYRK1A). Extensive molecular simulation studies have been performed on the relevant kinases to explain the strong affinity of this molecule on CLKs, as well as its selectivity against DYRK1A.
Asunto(s)
Antineoplásicos/farmacología , Descubrimiento de Drogas , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Relación Estructura-Actividad , Quinasas DyrKRESUMEN
A facile oxidative dearomatization of N-(p-methoxyaryl)propiolamides has been established for the synthesis of spiro-fused 2,5-cyclohexadienone frameworks via thio(seleno)cyanative ipso-cyclization in the presence of ceric ammonium nitrate (CAN) as the oxidant. The present method, involving the formation of C-S and C-C bonds, was also extended to (p-methoxyaryl)propiolates for thiocyanative ipso-cyclization. Furthermore, the obtained chalcogeno-spirocyclohexadienones were transformed into uniquely functionalized spirocyclohexadienone derivatives.
RESUMEN
Reported herein are the Rh(III)-catalyzed cascade annulation reactions of N-(pivaloyloxy)benzamides with 1,5-enynes to access diversely substituted aromathecin derivatives involving C-H activation. The developed procedure offers an efficient synthetic tool for the assembly of a wide range of N-(pivaloyloxy)benzamides and 1,5-enynes with good atom economy and functional group tolerance. The key reactions involved in this annulation are alkyne insertion and aza-Michael addition under oxidant-free mild reaction conditions.
RESUMEN
An unprecedented one-pot successive base-mediated allylic amination/cycloisomerization reaction strategy has been developed to construct diversely substituted imidazo[1,2-a]pyridines and benzimidazo[1,2-a]pyridines in good to excellent yield. The advantage of this unique [4 + 2]-annulation lies in the employment of readily accessible starting materials, Morita-Baylis-Hillman acetates of acetylenic aldehydes as C4 synthons, and simple imidazoles or benzimidazoles as C2 synthons.
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Harnessing of Morita-Baylis-Hillman (MBH) carbonates of acetylenic aldehydes as handy synthons has allowed a facile synthesis of azaspirocyclohexadienones by sequential DABCO-promoted sulfonamidation/ICl-mediated ipso-iodocyclization reactions. A variety of MBH-carbonates having aryl or heteroaryl groups on the alkyne functionality fruitfully participated in the one-pot ipso-annulation reaction to provide the corresponding 3-iodo spirocyclohexadienones. The sulphonamide functionality was further utilized to construct the tricyclic fused-sultam framework.
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An efficient and practical one-pot [4 + 2] benzannulation method to produce highly substituted indoles and 1-benzothiophenes via sequential acid-catalyzed propargylation/base-mediated cycloisomerization reactions has been developed. This method allows access to differently substituted (mainly on phenyl ring) indoles and 1-benzothiophenes from the reaction of 3-alkenylpyrroles/-thiophenes as C4 synthons with 1-aryl/1-heteroaryl propargylic alcohols as C2 synthons. Interestingly, dialkynyl substrates can undergo tandem benzannulations to give substituted aza[5]helicenes in 82-83% yield.
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A novel one-pot [4+2]-benzannulation approach to substituted carbazoles is accomplished by acid-catalyzed C3-propargylation of 2-alkenyl/aryl indoles with 1-aryl propargylic alcohols, followed by cycloisomerization. A variety of 2-alkenylated indoles and 2-aryl/heteroaryl indoles successfully participated in this tandem reaction with 1-aryl/heteroaryl propargylic alcohols to provide diversely substituted and annulated carbazoles, as well as an aza[5]helicene.
RESUMEN
The first asymmetric total synthesis of a new natural piperidine alkaloid, microcosamine A, has been accomplished from d-serine and d-methyl lactate as chiral pool starting materials. Key features of the strategy include the utility of Horner-Wadsworth-Emmons reaction, Luche reduction, intramolecular carbamate N-alkylation to form the piperidine framework and Julia-Kocienski olefination to install the triene side-chain.
Asunto(s)
Productos Biológicos/síntesis química , Piperidinas/síntesis química , Productos Biológicos/química , Estructura Molecular , Piperidinas/químicaRESUMEN
A novel and efficient method for the synthesis of diversely functionalized furans is developed via DBU-mediated tandem Michael addition/5-exo-dig-cycloisomerization of enynes and keto-methylenes. This [3 + 2]-annulation is operationally simple under metal-free reaction conditions with 100% atom economy and broad substrate scope.