Efficient synthesis of peptaibol using a chloroimidazolidium coupling reagent, CIP

Two peptaibols, alamethicin F-30 and trichovirin I 4A, have been synthesized in solution by using a 2-chloro-1,3-dimethylimidazolidium hexafluorophosphate in the presence of an additive (CIP-additive) as a coupling agent and TFA as a final deprotecting reagent. Alamethicin F-30 is one of the most common peptaibols and consists of 19 amino acids including 8 alpha,alpha-dimethyl amino acid (aminoisobutylic acid, Aib) and phenylalaninol residues. Trichovirin I 4A consists of 13 amino acids including 5 Aib residues and leucinol. In the synthesis of both, all couplings including those between sterically hindered Aib residues were successfully achieved within 60 min using a newly developed coupling agent, the CIP-additive. In the synthesis of trichovirin I 4A, no racemization was detected during the CIP-mediated coupling of peptide fragments having an optically active alpha-amino acid at its C-terminus. The synthesis of 2 peptaibols shows that the CIP-additive method is efficient not only for the coupling of sterically hindered amino acids but also for general fragment coupling. Copyright (C) 1996 Elsevier Science Ltd