RESUMEN
Oxa- and azabicyclic alkenes can be readily activated by transition-metal complexes with facial selectivity, because of the intrinsic reactivity of strained bicyclic structures. Synthetically, these compounds are important synthons that offer an important platform for the construction of biologically/medicinally significant compounds with two or more stereocenters. This Review comprehensively compiles the diverse catalytic processes involving the enantioselective transformations of oxa- and azabicyclic alkenes. It has been organized according to reaction type, including asymmetric ring opening (ARO) reactions, hydrofunctionalizations, cycloadditions and C-H activation reactions. The ARO section has been subdivided based on the type of nucleophiles employed, and further subdivided based on the metal used, with a separate topic dedicated to asymmetric ring-opening metathesis. Lastly, the presentation of each method/group of reactions is accompanied by concise discussions on their advantages and limitations.
RESUMEN
A site-selective dual C-7 and C-6 C-H functionalization of indolines with azabenzonorbornadienes has been accomplished using Rh-catalysis. The reaction affords a potential route toward pyrrolocarbazoles with broad scope and functional group tolerance.
RESUMEN
A simple, efficient and green procedure for the synthesis of novel 2,4-diaryl-5,6-dihydrobenzo[j][1,7]phenanthrolines has been developed via a Krohnke-type one-pot three-component reaction of 2-[arylmethylidene]-3,4-dihydro-1(2H)-acridinones and (2-aryl-2-oxoethyl)pyridinium bromides in the presence of excess ammonium acetate in good yields under solvent-free conditions. Good functional group tolerance, high substrate scope and no column purification are the practical advantages of this methodology.
Asunto(s)
Fenantrolinas/síntesis química , Técnicas de Química SintéticaRESUMEN
An efficient one-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo[3,4-c]pyrrole]-tetraone derivatives through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from ninhydrin and sarcosine with a series of 1-aryl-1H-pyrrole-2,5-diones is described. The synthesised compounds were screened for their antimycobacterial and AChE inhibition activities. Compound 4b (IC50 1.30µM) has been found to display twelve fold antimycobacterial activity compared to cycloserine and it is thirty seven times more active than pyrimethamine. Compound 4h displays maximum AchE inhibitory activity with IC50 value of 0.78±0.01µmol/L.
Asunto(s)
Acetilcolinesterasa/metabolismo , Antituberculosos/síntesis química , Microondas , Pirroles/química , Acetilcolinesterasa/química , Antituberculosos/química , Antituberculosos/farmacología , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Cristalografía por Rayos X , Diseño de Fármacos , Activación Enzimática/efectos de los fármacos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Pirroles/síntesis química , Pirroles/farmacología , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07µM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56µM) and 6l (IC50=2.87µM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16µmol/L respectively.
Asunto(s)
Acetilcolinesterasa/metabolismo , Antibacterianos/farmacología , Antineoplásicos/farmacología , Inhibidores de la Colinesterasa/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/química , Cromonas/química , Cromonas/farmacología , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Indenos/química , Indenos/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Pirrolidinas/química , Pirrolidinas/farmacología , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Estereoisomerismo , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/farmacologíaRESUMEN
A novel protocol for the synthesis of 3-nitro-N-aryl/alkylthiophen-2-amines in good yields from the reaction of α-nitroketene N,S-aryl/alkylaminoacetals and 1,4-dithiane-2,5-diol in the presence of K2CO3 in refluxing ethanol is described. This transformation generates two C-C bonds in a single operation and presumably proceeds through a reaction sequence comprising 2-mercaptoacetaldehyde generation, nucleophilic carbonyl addition, annelation and elimination steps.
RESUMEN
Cobalt(ii)-catalyzed stereospecific coupling of N-methylanilines with styrene oxides is developed via tandem C-N and C-O bond formation using tert-butyl hydroperoxide (TBHP) as an oxidant. Optically active epoxide can be reacted with high optical purity.
RESUMEN
The combinatorial syntheses of a library of novel dihydrothiophenone-engrafted dispiro oxindole/indenoquinoxaline-pyrrolidine/pyrrolothiazole/indolizine hybrid heterocycles have been realized through a chemo-, regio-, and stereoselective multicomponent 1,3-dipolar cycloaddition strategy.
Asunto(s)
Compuestos Heterocíclicos de Anillos Fusionados/síntesis química , Bibliotecas de Moléculas Pequeñas/síntesis química , Compuestos de Espiro/síntesis química , Tiofenos/síntesis química , Técnicas Químicas Combinatorias , Reacción de Cicloadición , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A library of novel dispiro compounds containing oxindole pyrrolidine/oxindolopyrrolothiazole-thiochroman-4-one hybrid frameworks has been synthesized in a fully regio- and stereoselective fashion by the three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the condensation of isatins and secondary amino acids (sarcosine/l-thioproline) with 3-arylidenethiochroman-4-ones. This experimentally simple protocol provides good yields of structurally complex, biologically relevant heterocycles in a single operation.
Asunto(s)
Reacción de Cicloadición/métodos , Indoles/síntesis química , Pirrolidinas/síntesis química , Bibliotecas de Moléculas Pequeñas , Tiazoles/síntesis química , Agroquímicos , Aminoácidos/química , Diseño de Fármacos , Compuestos Heterocíclicos/síntesis química , Oxindoles , Preparaciones Farmacéuticas/químicaRESUMEN
The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the reaction of isatins or acenaphthylene-1,2-dione and 1,3-thiazolane-4-carboxylic acid to various exocyclic dipolarophiles synthesized from estrone afforded a library of novel C-16 spiro oxindole or acenaphthylene-1-one - 7-(aryl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole - estrone hybrid heterocycles. These reactions occur regio- and stereo-selectively affording a single isomer of the spiro estrones in excellent yields with the formation of two C-C and one C-N bonds along with the generation of four new contiguous stereo-centers in a single step.