Construction of dansylated (fluorescent) amino acid motifs via C(sp3)–H arylation

Abstract

We describe the construction of a library of novel dansylated (fluorescent) phenylalanine-type unnatural amino acid scaffolds using a Pd(II)-catalyzed C(sp³)–H arylation method. A literature survey revealed that, in general, the dansyl moiety is introduced at the N-terminus of amino acids. Various dansylated amino acids and peptides have been used as fluorophores or probes and are known to show promising biological activities. Our strategy involved the introduction of dansylated anilines into the backbone of amino acids via a Pd(II)-catalyzed 8-aminoquinoline directing group-aided β-C(sp³)–H arylation strategy. We have assembled novel racemic/enantioenriched dansylated α-amino acid scaffolds using norvaline, phenylalanine, leucine, norleucine, and non-α-amino acid derivatives. A preliminary study was conducted to show the application of representative dansylated phenylalanine-type molecules for detecting metal cations. We conducted screening of a library of 58 small molecules (10 μM), and identified compounds 18a-(L) and 20b-(D) as potent inhibitors of IAV infection in the human lung alveolar cell line A549.