Credit: © 2009 NPG

α-Amino acids are not only the building blocks of proteins: they are widely found in chiral catalysts or ligands and drug molecules, such as the HIV drug Atazanavir. In many cases, however, unnatural amino acids or the unnatural enantiomers of amino acids are required because they provide higher activity or selectivity. Methods for the stereoselective synthesis of amino acids are therefore in constant demand.

Enantioselective enamine hydrogenation is a common method, but is not useful for the synthesis of amino acids with α-aryl or α-quaternary-alkyl substituents. Another option — the asymmetric Strecker synthesis — has, until now, rarely been applied on a large scale owing to the need to use hazardous cyanide sources and the requirement for cryogenic conditions. Now, Eric Jacobsen and co-workers from Harvard University have developed1 an asymmetric Strecker synthesis that allows the use of safer cyanide salts and does not require such drastic cooling to achieve high selectivity.

The thiourea catalyst is similar to those that the group has previously reported, but it has a simpler structure and is effective in aqueous solvents, thus allowing the use of potassium cyanide. The new catalyst allowed the production of tert-leucine — which interestingly is a recognisable component of the catalyst itself — on a 100 mmol scale.