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New β,β‐Bis(benzo[ b ]thienyl)dehydroalanine Derivatives: Synthesis and Cyclization
Author(s) -
Abreu Ana S.,
Silva Natália O.,
Ferreira Paula M. T.,
Queiroz MariaJoão R. P.,
Venanzi Mariano
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300394
Subject(s) - dehydroalanine , chemistry , trifluoroacetic acid , triethylamine , suzuki reaction , stereochemistry , medicinal chemistry , amino acid , organic chemistry , palladium , catalysis , biochemistry
The methyl ester of β,β‐dibromo‐ N ‐( tert ‐butoxycarbonyl)dehydroalanine was synthesized by treating the methyl ester of N , N ‐bis( tert ‐butoxycarbonyl)dehydroalanine with trifluoroacetic 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 β,β‐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 %), Na 2 CO 3 (4 equiv.) in DME/H 2 O (10:1). The Suzuki cross‐coupling products were treated with Pd(OAc) 2 and Cu(OAc) 2 in DMF at 160 °C 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)