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Advisor(s)
Abstract(s)
Several benzo[b]thienyldehydrophenylalanines were synthesized from pure stereoisomers of the methyl ester of N-(tertbutoxycarbonyl)-
b-bromodehydrophenylalanine as an extension of our previously reported method for the synthesis of dehydrotryptophan
analogues to dehydrophenylalanine derivatives. The latter were obtained in high yields by N-deprotection and bromination of N,N-bis-(tertbutoxycarbonyl)-(
Z)-dehydrophenylalanine using TFA and NBS. This was carried out in two steps or in a one pot procedure resulting in
different E/Z ratios. These compounds were coupled under Suzuki cross-coupling conditions [Pd(PPh3)4, Na2CO3, DME/H2O] with several
boronic benzo[b]thienyl acids in good to high yields maintaining the stereochemistry of the starting materials. The best yields were obtained
when the boronic acid was in position 7 of the benzo[b]thiophene and with the E isomer of the brominated dehydrophenylalanine. In some
cases it was possible to increase the lower yields by changing the Pd source to PdCl2(PPh3)2. A model dipeptide was prepared coupling a
benzo[b]thienyldehydrophenylalanine with the methyl ester of alanine. Preliminary antimicrobial studies were performed with both isomers
of one of the b, b-diaryldehydroalanines obtained. The results show that the compounds are selective and very active (very low MICs) against
Gram positive bacteria (B. cereus and B. subtilis) the Z-isomer being more active. The compounds are also active against Candida albicans
presenting similar MICs.
Description
Keywords
Amino acids Dehydrophenylalanines Benzo[b]thiophenes Suzuki coupling Palladium Antimicrobial
Citation
Abreu, Ana S.; Ferreira, Paula M.T.; Monteiro, Luís S.; Ferreira, Isabel C.F.R.; Calhelha, Ricardo C.; Estevinho, Leticia M. (2004). Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity. Tetrahedron. ISSN 0040-4020. 60:54, p. 11821-11828
Publisher
Elsevier