Synthetic studies of bacitracin. I. Synthesis of a protected intermediate heptapeptide (5-11).

Abstract

Abstract A protected heptapeptide, the formyl-l-isoleucyl-ε-benzyloxycarbonyl-l-lysyl-δ-5-tosyl-d-ornithyl-l-isoleucyl-d-phenylalanyl-im-benzyl-l-histidyl-l-aspartic acid α-methyl-β-benzyl ester, was synthesized by the azide method and the carbodiimide method. It is an intermediate peptide for the total synthesis of the antibiotic bacitracin A, the structure of which is still ambiguous at a few points. β-Benzyl benzyloxycarbonyl-l-aspartate was prepared by a novel method similar to that used in the synthesis of γ-benzyl glutamate. The α-methyl-β-benzyl l-aspartate prepared could be useful in the synthesis of branched aspartic acid peptide. Phenomena of dimorphism were observed in crystals of δ-tosyl-d-ornithine and δ-tosyl-d-ornithyl-l-isoleucyl-d-phenylalanine ethyl ester hydrobromide, and two crystal forms of each compound were isolated in pure states.