Synthesis of β-benzo[b]thienyldehydrophenylalanine derivatives by one-pot palladium-catalyzed borylation and suzuki coupling (BSC) and metal-assisted intramolecular cyclization: studies of fluorescence and antimicrobial activity

• Autor(a) principal: Abreu, Ana S.
• Data de Publicação: 2005
• Outros Autores: Ferreira, Paula M.T., Queiroz, Maria João R.P., Ferreira, Isabel C.F.R., Calhelha, Ricardo C., Estevinho, Leticia M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10198/823
• topic: Dehydrophenylalanines; Benzothiophenes; Borylation; Suzuki coupling; Cyclization; Indoles; Fluorescence; Antimicrobial activity

Palladium-catalyzed borylation and Suzuki coupling (BSC) in a one-pot procedure was successfully applied to the synthesis of several β-substituted dehydrophenylalanines in the benzo[b]thiophene series, with the stereochemistry of the starting materials being maintained. Bromobenzo[b]thiophenes bearing an ortho EDG (OMe or Me) were used as the components to be borylated with pinacolborane, whilst pure stereoisomers of β-bromodehydrophenylalanines were used as the other Suzuki coupling components. Treatment of the obtained methyl ester of (Z)-N-(tert-butoxycarbonyl)-β- (2,3,5-trimethylbenzo[b]thien-6-yl)dehydrophenylalanine with Pd(OAc)2 and Cu(OAc)2 in DMF at 160 °C gave two in dole derivatives (1:3), the major product resulting from isomerization and cyclization and the minor product resulting from direct cyclization (thienoindole). Carrying out the reaction at 100 °C gave the same products in similar amounts. Use of the methyl ester of (Z)-N-(tert-butoxycarbonyl)-β- (2,3,7-trimethylbenzo[b]thien-6-yl)dehydrophenylalanine as starting material gave only one product, resulting from isomerization and cyclization at 100 °C. Two of the cyclized compounds were subjected to fluorescence studies; the thienoindole could be useful as a fluorescent probe. Preliminary studies of antimicrobial activity were performed on the precursors and on the cyclized products.