RESUMO
Total syntheses of (+)-dictyoceratin-C (1) and (+)-dictyoceratin-A (smenospondiol) (2), hypoxia-selective growth inhibitors isolated from marine sponge, were executed. The absolute stereochemistry of the each compound was determined through the enantioselective total syntheses of them. It revealed that the unnatural enantiomers of them also exhibited the hypoxia-selective growth inhibitory activity against human prostate cancer DU-145 cells.
Assuntos
Proliferação de Células/efeitos dos fármacos , Inibidores do Crescimento/síntese química , Inibidores do Crescimento/farmacologia , Hidroxibenzoatos/síntese química , Hidroxibenzoatos/farmacologia , Poríferos/química , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Animais , Hipóxia Celular , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores do Crescimento/química , Humanos , Hidroxibenzoatos/química , Masculino , Biologia Marinha , Neoplasias da Próstata/patologia , Sesquiterpenos/química , EstereoisomerismoRESUMO
A four-step regioselective synthesis of multisubstituted isoquinoline derivatives from 3-bromopyridines was developed by the Diels-Alder (DA) reactions of 2-silyl-3,4-pyridynes with furans, followed by functional-group transformations. In particular, the silyl group at the C2-position of the 3,4-pyridynes played two important roles: firstly, it functioned as the directing group for the DA reaction, and secondly, it served to introduce diverse substituents at the C1-position of the isoquinolines by electrophilic ipso-substitution.
