Synthesis and Fluorescent Properties of β-Pyridyl α-Amino Acids

The preparation of a new class of β-pyridyl α-amino acid is described using a highly regioselective, ytterbium-catalyzed hetero-Diels–Alder reaction of enones with vinyl ethers followed by a modified Knoevenagel–Stobbe reaction as the key heterocycle forming steps. Investigation of the properties and applications of these amino acids showed that they could be utilized in solid phase peptide synthesis for the preparation of a biologically relevant hexapeptide, while pyridines bearing electron-rich substituents exhibited strongly fluorescent properties with high quantum yields and MegaStokes shifts. A solvatochromic study with the most fluorogenic amino acid, a p-methoxyphenyl analogue, revealed that this charge-transfer based chromophore is highly sensitive to solvent polarity with a bathochromic shift of 115 nm on changing from THF to phosphate-buffered saline.