RESUMO
An elegant reagent-controlled strategy has been developed for the generation of a diverse range of biologically active scaffolds from a chiral bicyclic lactam. Reduction of the chiral lactam with LAH or alkylation with LHMDS to trigger different cyclization reactions have been shown to generate privileged scaffolds, such as pyrrolidines, indolines, and cyclotryptamines. Their amenability to substitution allows us to create various compound libraries by using these scaffolds. Inâ silico studies were used to estimate the drug-like properties of these compounds. Selected compounds were subjected to anticancer screening by using three different cell lines. In addition, all these compounds were subjected to antibacterial screening to gauge the spectrum of biological activity that was conferred by our DOS methodology. Gratifyingly, with no additional iterative cycles, our method directly generated anticancer compounds with potency at low nanomolar concentrations, as represented by spiroindoline 14.
Assuntos
Antibacterianos/síntese química , Antineoplásicos/síntese química , Compostos Heterocíclicos/síntese química , Lactamas Macrocíclicas/química , Compostos de Espiro/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclização , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Humanos , Metilação , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Peso Molecular , Compostos de Espiro/química , Compostos de Espiro/farmacologiaRESUMO
A highly efficient enantioselective S(N)Ar reaction of chiral acyl bicyclic lactam with substituted-2,4-dinitrobenzenes was developed, affording products containing quarternary stereogenic centers. They are further utilized towards an enantioselective synthesis of spirooxoindoles.
