Non-canonical amino acids bearing thiophene and bithiophene: synthesis by an Ugi multicomponent reaction and studies on ion recognition ability

Abstract

Novel thienyl and bithienyl amino acids with different substituents were obtained by a multicomponent Ugi reaction between a heterocyclic aldehyde, an amine, an acid and an isocyanide. Due to the presence of the sulphur heterocycle at the side chain, these unnatural amino acids are highly emissive and bear extra electron donating atoms so they were tested for their ability to act as fluorescent probes and chemosensors in the recognition of biomedically relevant ions in acetonitrile and acetonitrile/water solutions. The results obtained from spectrophotometric/spectrofluorimetric titrations in the presence of organic and inorganic anions, and alkaline; alkaline-earth and transition metal cations indicated that the bithienyl amino acid bearing a methoxy group is a selective colorimetric chemosensor for Cu, while the other (bi)thienyl amino acids act as fluorimetric chemosensors with high sensitivity towards Fe and Cu in a metal-ligand complex with 1:2 stoichiometry. The photophysical and ion sensing properties of these amino acids confirm their potential as fluorescent probes suitable for incorporation into peptidic frameworks with chemosensory ability.

Review on the Ugi Multicomponent Reaction Mechanism and the Use of Fluorescent Derivatives as Functional Chromophores

“…A close look in the literature will show the readers a few more examples − (only five) of functional chromophore derivatives synthesized using the Ugi MCR applying the scaffold approach. This is a clear indication of the vast field to be explored in the next years by using these two approaches (Figure ).…”

Electrochemical Synthesis of Unnatural Amino Acids Embedding 5- and 6-Membered Heteroaromatics

“…Yet, a wide range of heterocycles could be obtained in one-pot using the methodology described. For instance, thiophene-containing UAAs 11 and 12 , potentially useful as fluorescent chemosensors, 24 were obtained in up to 30% yields. Thiazole, another ubiquitous 5-membered ring in medicinal chemistry, could be embedded too, as reported for UAAs 13 – 16 .…”

Electrochemical Synthesis of Unnatural Amino Acids Embedding 5- and 6-Membered Heteroaromatics

“…Yet, a wide scope of heterocycles could be obtained in one-pot using the methodology described. For instance, thiophene-containing UAAs 11 and 12, potentially useful as fluorescent chemosensors, 23 were obtained up to 30%. Thiazole, another ubiquitous 5-membered ring in medicinal chemistry, could be embedded too, as reported for UAAs 13-16.…”