RESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Fenantrolinas/síntese química , Técnicas de Química SintéticaRESUMO
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.
Assuntos
Acetilcolinesterase/metabolismo , Antituberculosos/síntese química , Micro-Ondas , Pirróis/química , Acetilcolinesterase/química , Antituberculosos/química , Antituberculosos/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cristalografia por Raios X , Desenho de Fármacos , Ativação Enzimática/efeitos dos fármacos , Concentração Inibidora 50 , Testes de Sensibilidade Microbiana , Conformação Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Pirróis/síntese química , Pirróis/farmacologia , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Acetilcolinesterase/metabolismo , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Inibidores da Colinesterase/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Cromonas/química , Cromonas/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indenos/química , Indenos/farmacologia , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Pirrolidinas/química , Pirrolidinas/farmacologia , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacologiaRESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Compostos Heterocíclicos de Anéis Fundidos/síntese química , Bibliotecas de Moléculas Pequenas/síntese química , Compostos de Espiro/síntese química , Tiofenos/síntese química , Técnicas de Química Combinatória , Reação de Cicloadição , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Reação de Cicloadição/métodos , Indóis/síntese química , Pirrolidinas/síntese química , Bibliotecas de Moléculas Pequenas , Tiazóis/síntese química , Agroquímicos , Aminoácidos/química , Desenho de Fármacos , Compostos Heterocíclicos/síntese química , Oxindóis , Preparações Farmacêuticas/químicaRESUMO
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.