Synthesis of pelargonoyl-cyclic decapeptide analog of the antibiotic polymyxin B.1

The synthesis of pelargonoyl-cyclic decapeptide, analog of polymycin B1, is described. The open-chain protected decapeptide was synthesized on a polymer support, starting with threonine as the C-terminal amino acid residue, and was cleaved satisfactorily by hydrazinolysis. The alpha-amino protecting Boc-group was removed with HCl (1 mol/l) acetic acid and the resulting decapeptide hydrazide was converted to the azide with nitrous acid. Cyclization of the azide in pyridine at peptide concentration 2.5.10(-5) mol/l gave the penta-benzyloxycarbonyl-substituted decapeptide in 65% yield. Catalytic hydrogenation afforded the pelargonoyl cyclic decapeptide pentahydrochloride (6) in 75% yield. The synthetic product (6) exhibited an activity comparable to that of the natural polymyxin B1 against Bacillus subtilis and Staphylococcus aureus, whereas it showed only 2% of the activity to Escherichia coli2.