Protease-catalysed synthesis of Z-l-aminoacyl-l-caprolactam amides from Z-protected amino acid esters and dl-α-amino-ε-caprolactam

The enzymatic synthesis of Z-l-aminoacyl-l-caprolactam amides from Z-protected amino acid esters and dl-α-amino-ε-caprolactam (ACL) was accomplished by the thiol proteases papain, bromelain and ficin in aqueous–organic media. Product yields of 96% and 87% for Z-Gly-l-ACL and Z-Ala-l-ACL, respectively, could be obtained. The products were purified and characterised by polarimetry, NMR and LC–MS. The suitability to accept a bulky 1,2-amino ketone as a nucleophile expands the general knowledge of thiol proteases and their catalytic potential.