Variants of the azlactone synthesis in which analogues of azlactones are used are sometimes advantageous.Hydantoin (in Bergmann modification),thiohydantoin andrhodanine have each been employed as the enolate-forming component of the condensation.[5][6]2,5-Diketopiperazine can be used as a methylene component as well; its condensation products with aromatic aldehydes, on reduction and hydrolysis give the corresponding amino acids.[7][8][9]
^H.D. Dakin. Aromatic aldehyde derivatives of proteins, peptides and amino acids. J. Biol. Chem. 1929, 84:675-682
^Alan D. Borthwick. 2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products. DrugMolDesign, 15 Temple Grove, London NW11 7UA, U.K. Chem. Rev., 2012, 112 (7), pp 3641–3716. DOI: 10.1021/cr200398y
^A. M. Asiri. New Conjugated Systems Derived from Piperazine-2,5-dione. Molecules 2000, 5, 629-636
^Cara E. Humphrey, Markus Furegati, Kurt Laumen, Luigi La Vecchia, Thomas Leutert, J. Constanze D. Müller-Hartwieg, and Markus Vögtle (2007). "Optimized Synthesis ofL-m-Tyrosine Suitable for Chemical Scale-Up".Organic Process Research & Development.11 (6):1069–1075.doi:10.1021/op700093y.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Thebenzyl ether of3-hydroxybenzaldehyde1 reacts with the N-acetylamide ofglycine2,acetic anhydride andsodium acetate to the azlactone (not displayed) which is ring-opened with sodium acetate in methanol to dehydroamino acid3.Hydrogenation gives the N-acyl-m-tyrosine methyl ester4 (the benzyl ether group is also cleaved). This compound isracemic andkinetic resolution is brought about by anenzyme which is able to only cleave the methyl ester of the S-enantiomer (forming (S)-5 soluble indichloromethane) leaving water-soluble (R)-4 untouched. The final step is amide cleavage to (S)-L-m-tyrosine6
