Synthesis of pure stereoisomers of benzo[b]thienyl dehydrophenylalanines by Suzuki cross-coupling. Preliminary studies of antimicrobial activity

Abstract

Abstract-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(PPh 3 ) 4 , Na 2 CO 3 , DME/H 2 O] 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 PdCl 2 (PPh 3 ) 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. q

The effect of β‐methylation on the conformation of α, β‐dehydrophenylalanine: a DFT study

“…Among β,β′‐disubstituted dehydroamino acids β‐(pyren‐1‐yl)dehydroaminobutyric acid and β‐(pyren‐1‐yl)dehydrophenylalanine derivatives were prepared to evaluate their electrochemical and photophysical properties as these may be potentially useful for conformational studies of peptides and proteins32. Also, β,β′‐diaryldehydroalanines were studied and some preliminary antimicrobial properties reported33.…”

Incorporation of 2-amino-thiophene derivative in nanoparticles: enhancement of antifungal activity

“…According to Abreu et al [25] and Mohareb et al [26], compounds containing thiophene rings possess selective and significant antifungal activity against C. albicans. In accordance with Ram et al [27], strains of Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Trichophyton mentagrophytes, and Sporothrix schenckii were sensitive to the analogous thiophene evaluated in the present work.…”

High yielding synthesis of N-ethyl dehydroamino acids

“…Synthesis of the methyl esters of N-protected -halo dehydroamino acids Synthesis of compounds Boc-Ala(,-Br)-OMe (4c) (Silva et al 2002), Z(NO 2 )-E-Abu(-Br)-OMe (E-5a) (Ferreira et al 2007), Z(NO 2 )-Z-Abu(-Br)-OMe (Z-5a) (Ferreira et al 2007), Z-Z-Abu-(-Br)OMe (Z-5b) (Ferreira et al 2007), Boc-E-Abu(-Br)-OMe (E-5c) (Silva et al 2002), Boc-Z-Abu(-Br)-OMe (Z-5c) (Silva et al 2002), Z(NO 2 )-Z-Phe(-Br)-OMe (Z-6a) (Monteiro et al 2011), Z-Z-Phe(-Br)-OMe (Z-6b) (Monteiro et al 2011), Boc-Z-Phe(-Br)-OMe (Z-6c) (Abreu et al 2004), Boc-Z-Phe(-I)-OMe (Z-7c) (Queiroz et al 2008).…”