RESUMEN
Thio and seleno analogues of tetramethylrosamine were prepared by the directed-metalation/cyclization of the corresponding N,N-diethyl 2-(3-dimethylaminophenylchalcogeno)-4-dimethylaminobenzamide to the 2,7-bis-(N,N-dimethylamino)-9H-chalcogenoxanthen-9-one followed by the addition of phenylmagnesium bromide, dehydration, and ion exchange to the chloride salt. The thio and seleno tetramethylrosamines had longer wavelengths of absorption and higher quantum yields for the generation of singlet oxygen than tetramethylrosamine. Both the thio and selenoanalogues of tetramethylrosamine were efficient photosensitizers against R3230AC rat mammary adenocarcinoma cells in vitro.
Asunto(s)
Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Compuestos Heterocíclicos con 3 Anillos/farmacología , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/farmacología , Compuestos de Selenio/síntesis química , Compuestos de Selenio/farmacología , Animales , Línea Celular Tumoral , Supervivencia Celular , Calcógenos/química , Espacio Intracelular/ultraestructura , Espectrometría de Masas , Microscopía Confocal , Estructura Molecular , Fármacos Fotosensibilizantes/química , Ratas , Rodaminas , Selenio/química , Compuestos de Selenio/química , Azufre/químicaRESUMEN
The reaction of N, N-diethyl 4-(N', N'-dimethylamino)-2-phenylselenobenzamide (7a), N, N-diethyl 4-methoxy-2-phenylselenobenzamide (7b), N, N-diethyl 4-(N', N'-dimethylamino)-2-[(3-(N, N-dimethylamino)phenylseleno]benzamide (7c), and N, N-diethyl 4-methoxy-2-(3-methoxyphenylseleno)-benzamide (7d) with excess lithium diisopropylamide (LDA) gave 2-N, N-(dimethylamino)-9H-selenoxanthone (9a), 2-methoxy-9H-selenoxanthone (9b), 2,7-bis-N, N-(dimethylamino)-9H-selenoxanthone (9c), and 2,5-dimethoxy-9H-selenoxanthone (9d) in 70%, 59%, 23%, and 90% isolated yields, respectively. N, N-Diethyl 2-phenylselenobenzamide (2-Se) gave no reaction with LDA, t-BuLi, MeLi, or lithium 2,2,6,6-tetramethylpiperidide as base. Electron donation from the 4-substituent of benzamide derivatives 7a-7d may increase the directing ability of the carbonyl oxygen to metalate the 2-position of the arylseleno group.