Recent advances in the synthesis of unnatural α-amino acids

The synthesis of unnatural alpha-amino acids is an area of research that has gained a lot of attention in recent years. The availability of synthetic methods for novel unnatural alpha-amino acid derivatives and related compounds will be a critical point in the de novo design of molecules that mimic the conformation of the natural, active peptides. These molecules (peptidomimetics) are designed to display high receptor affinity and selectivity, in addition to enhanced bioavailability and metabolic stability. This review focuses on selected recent synthetic methodologies leading to unnatural alpha-amino acids including chiral catalysts that enable enantioselective synthesis and microwave-assisted synthesis. Solid phase synthesis and construction of organometallic alpha-amino acids reveal the scope of influence that this field has in organic chemistry. Additionally, the article is aimed to provide a brief insight into the biosynthetic approaches to the synthesis of alpha-amino acid derivatives, and to give the reader an appreciation of the field.