Emerging progress in chiral phosphoric acid-catalyzed asymmetric synthesis of unnatural α-amino acids

Unnatural α-amino acids (α-UAAs) are essential components in the development of biologically active compounds, pharmaceuticals, ligands, and catalysts. They are widely used in drug discovery and protein engineering, seamlessly integrating into linear or cyclic peptides and proteins to enhance their biological effectiveness. As a result, there is a high demand for the asymmetric synthesis of these unnatural amino acids, with a specific emphasis on the environmentally friendly pathway for their development, particularly through the use of chiral phosphoric acid. Chiral phosphoric acids (CPAs) are a versatile group of Brønsted acid organocatalysts that have gained popularity in recent years for their role in the asymmetric synthesis of amino acids. This method provides a wide range of unnatural α-amino acids with precise stereochemical control. However, ongoing research is crucial to discover novel unnatural α-amino acids with unique side chains and chirality to surpass the limitations of their natural counterparts. This review focuses on the chiral phosphoric acid (CPA)-catalyzed approach for the asymmetric synthesis of α-UAAs that are reported post 2015.