No abstract

Nagarse, papain, pepsin and thermolysin were found to catalyze the peptide bond formation between two amino acids or peptides, one protected with a suitable group at the amino group and the other at the carboxyl group. Experiments with various combinations of amino acids and dipeptides show specificity in the catalytic action in varying degree which depending on the nature of the enzyme. Since the condensation takes place efficiently under mild conditions, this method opens up a useful way for the synthesis of peptides.

N δ-Tosyl-Nδ-benzyloxy-Dl-ornithine was synthesized starting from γ-(N-tosyl-N-benzyloxy)-aminopropyl bromide and diethyl acetamidomalonate and resolved enzymatically to give the l- and d-isomers. Removal of one or both of protecting groups gave Nδ-benzyloxyornithine or Nδ-hydroxyornithine. The reduction product of Nδ-hydroxy-l-ornithine was identical with authentic l-ornithine.

Acetylation of Nδ-benzyloxyornithine monohydrobromide (I·HBr) with acetic anhydride gave the Nδ-acetylated product, which yielded Nδ-acetyl-Nδ-hydroxyornithine by catalytic reduction. On the other hand, acetylation or alkoxycarbonylation of Nδ-benzyloxyornithine(I) proceeded through Nα-acetylation, followed by spontaneous cyclization to form lactams, which yielded cyclic hydroxamic acids on catalytic reduction. These hydroxamic acid and Nδ-acetyl-Nδ-hydroxyornithine were readily hydrolyzed to give Nδ-hydroxyornithine.

Two different sequence hexapeptides for the synthesis of ferrichrome were prepared using Nδ-tosyl-Nδ-benzyloxy-l-ornithine by means of N-hydroxysuccinimide plus N,N-dicyclohexylcarbodiimide or Woodward reagent K method. The linear hexapeptides (XII·HCl and XIX·HCl) were cyclized by excess N,N-dicyclohexylcarbodiimide to give cyclo-triglycyltri-Nδ-tosyl-Nδ-benzyloxy-l-ornithyl (XX). Detosylation, acetylation and successive reductive debenzylation of XX afforded deferri-ferrichrome (XXIV). Addition of ferric iron to XXIV gave ferrichrome, which had the same crystalline form, superimposable infrared and well-agreeing visible spectra and the same value in optical rotation compared with the data in the literature of natural product.