Application of Spontaneous Schiff Base Copper Chelates Formation Process to the Design of a Trypsin Inhibitor

Abstract

Salicylaldehyde derivatives carrying an amidinium group react spontaneously with α-amino acids in copper-containing aqueous media to afford very stable Schiff base copper chelates. A variety of Schiff base chelates were prepared from various α-amino acids. Each α-amino acid provides enantiomeric isomers due to the asymmetric α-carbon, except for glycine. Inhibitory activity of these amidinium chelates toward trypsin was generally very strong. Thus these compounds represent a novel series of potent trypsin inhibitors. The structure-activity relationship of the inhibitors is discussed based on their inhibition constants, though the variations are not large.