New β,β-bis(benzo[b]thienyl)dehydroalanine derivatives:: Synthesis and cyclization

The methyl ester of beta,beta-dibromo-N-(tert-butoxycarbonyl)-dehydroalanine was synthesized by treating the methyl ester of N,N-bis(tert-butoxycarbonyl)dehydroalanine with trifluo-roacetic acid, N-bromosuccinimide and triethylamine. This compound was then used in Suzuki cross-coupling reactions with several (benzo[b]thienyl)boronic acids to give the corresponding beta,beta-bis(benzo[b]thienyl)dehydroalanine derivatives in good to high yields (55-90 %). After several experiments, the best conditions were shown to be: (benzo[b]thienyl)boronic acid (5 equiv.), [Pd(PPh)(2)Cl-2] (20 mol %), Na2CO3 (4 equiv.) in DME/H2O (10:1). The Suzuki cross-coupling products were treated with Pd(OAc)(2) and Cu(OAc)(2) in DMF at 160 degreesC to give the (benzo[b]thienyl)pyrroles in moderate to good yields (25-62 %). Other attempts were carried out using only Cu(OAc)(2), the thienylpyrroles being, in some cases, isolated in lower yields. Preliminary fluorescence studies show that the (benzo[b]thienyl)pyrroles can be used as biomarkers. All of these compounds are non-proteinogenic amino acids that can have biological activity or can be used in conformational studies in order to establish structure-activity relationships. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)