RESUMEN
A new selective synthetic approach to indole derivatives bearing a tetrazole moiety has been developed. Arynes, generated in situ from o-(trimethylsilyl)aryl triflates and KF, reacted smoothly with 2-(2-benzyl-2H-tetrazol-5-yl)-2H-azirines to give 3-(2-benzyl-2H-tetrazol-5-yl)-indole derivatives with high selectivity. Deprotection of the tetrazole moiety gave 3-(1H-tetrazol-5-yl)-indole derivatives.
RESUMEN
This review aims to present the most recent contributions in the chemistry of nitrosoalkenes and azoalkenes, highlighting the chemical behavior that makes them important and versatile building blocks in organic synthesis. These are heterodienes used in the assembly of a variety of heterocyclic systems, spanning from five- to seven-membered heterocycles, as well as for the functionalization of heterocycles.
RESUMEN
A novel synthetic approach to bis(indolyl)methanes has been established. Our one-pot synthetic strategy based on two consecutive hetero-Diels-Alder cycloaddition reactions of electrophilic conjugated nitrosoalkenes with indoles was extended to a range of new 1-hydroxyiminomethyl-bis(indolyl)methanes. Furthermore, a similar and broad range approach was applied to the synthesis of previously unknown 1-hydrazonomethyl-bis(indolyl)methanes. The biological evaluation of the new bis(indolyl)methanes as anti-cancer agents was investigated.
Asunto(s)
Antineoplásicos/farmacología , Indoles/farmacología , Metano/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Reacción de Cicloadición , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indoles/síntesis química , Indoles/química , Metano/análogos & derivados , Metano/química , Estructura Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A versatile and broad range approach to previously unknown bis(indolyl)methane oximes based on two consecutive hetero Diels-Alder cycloaddition reactions of electrophilic conjugated nitrosoalkenes with indoles is disclosed. The cytotoxic properties and selectivity of some adducts against several human cancer cell lines pointing to a promising role in the development of anti-tumoural drugs, in particular for leukaemia and lymphoma.
Asunto(s)
Antineoplásicos/síntesis química , Diseño de Fármacos , Indoles/síntesis química , Oximas/síntesis química , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/química , Antineoplásicos/farmacología , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Reacción de Cicloadición , Humanos , Indoles/efectos adversos , Indoles/química , Indoles/farmacología , Macrófagos/efectos de los fármacos , Microglía/efectos de los fármacos , Oximas/efectos adversos , Oximas/química , Oximas/farmacología , Relación Estructura-ActividadRESUMEN
The reactivity of nitrosoalkenes toward dipyrromethanes, pyrrole, and 2,5-dimethylpyrrole is described. 1-(p-Bromophenyl)nitrosoethylene shows a different chemical behavior with these heterocycles than the previously reported reactions of ethyl nitrosoacrylate, which proceeds via a Diels-Alder reaction. 1-(p-Bromophenyl)nitrosoethylene reacts with dipyrromethanes and pyrrole to afford two isomeric oximes via conjugate addition followed by rearomatization of the pyrrole unit. On the other hand, this nitrosoalkene reacts with 2,5-dimethylpyrrole through an initial conjugate addition followed by intramolecular O- and N-nucleophilic addition with the formation of the corresponding bicyclic oxazine and five-membered cyclic nitrone, respectively. Quantum chemical calculations, at the DFT level of theory, indicate that the barriers associated with the Diels-Alder reactions of ethyl nitrosoacrylate are over 30 kJ/mol lower than those that would be required for the cycloadditions of 1-(p-bromophenyl)nitrosoethylene. Thus, calculations predict that the Diels-Alder reaction is privileged in the case of ethyl nitrosoacrylate and point to a different reaction pathway for 1-(p-bromophenyl)nitrosoethylene, corroborating the experimental findings.
RESUMEN
The phototransformation of benzimidazole (BZ) and of the benzimidazole pesticide thiabendazole (TBZ) was investigated in aqueous solution in the absence and presence of the supramolecular host cucurbit[8]uril (CB8). ESI-MS and NMR reveal that both compounds form stable 1 : 2 host-guest complexes with CB8 (BZ2@CB8, TBZ2@CB8). The phototransformation of free BZ leads to dehydrodimerization, while for TBZ the photoreactivity leads to BZ, benzimidazole-2-carboximide and 2-acetylbenzimidazole. Inside CB8, BZ undergoes photohydrolysis to form 2-aminoformanilide, while for TBZ2@CB8 additional photoproducts were observed which are pH dependent. At pH 1.2 photolysis of TBZ2@CB8 leads to new red-shifted photoproducts with extended π conjugation.
RESUMEN
The synthesis of 2-(tetrazol-5-yl)-2H-azirines is reported for the first time. Using the Neber approach, ß-ketoxime-1H-tetrazoles were converted into the target 2H-azirines bearing phenyl, furan-2-yl, thiophen-2-yl, or pyrrol-2-yl substituents at C-3. It was demonstrated that the alkaloid-mediated Neber reaction allows the asymmetric synthesis of 2-(tetrazol-5-yl)-2H-azirines.
Asunto(s)
Azirinas/síntesis química , Tetrazoles/síntesis química , Azirinas/química , Estructura Molecular , Tetrazoles/químicaRESUMEN
An overview of the use of 2H-azirines, conjugated nitrosoalkenes and conjugated azoalkenes bearing phosphorus substituents in addition and cycloaddition reactions is presented, focused on strategies for the synthesis of aminophosphonate and aminophosphine oxide derivatives.