SOLID-PHASE SYNTHESIS OF CYCLODODECADEPSIPEPTIDE VALINOMYCIN

The method of automated solid-phase peptide synthesis was applied to the preparation of the antibiotic valinomycin, a cyclic dodecadepsipeptide containing D-valyl, L-valyl, D-α-hydroxyisovaleryl, and L-lactyl residues. The open-chain depsipeptide was synthesized by coupling alternately the N-Boc-protected didepsipeptides L-valyl-D-α-hydroxyisovaleric acid and D-valyl-L-lactic acid to resin-bound D-valyl-L-lactate using dicyclohexylcarbodiimide as coupling agent. After cleavage from the resin the peptide was cyclized by the acid chloride method to give valinomycin. The crystalline product that was obtained in an overall yield of 33% had the same physical and chemical properties as the natural antibiotic and showed the same characteristics in making lipid bilayers selectively permeable to potassium ions. © 1969, American Chemical Society. All rights reserved.