EFFICIENT SYNTHESIS OF PEPTAIBOL USING A CHLOROIMIDAZOLIDIUM COUPLINGREAGENT, CIP

Two peptaibols, alamethicin F-30 and trichovirin I 4A, have been synth esized in solution by using a 2-chloro-1,3-dimethylimidazolidium hexaf luorophosphate in the presence of an additive (CIP-additive) as a coup ling agent and TFA as a final deprotecting reagent. Alamethicin F-30 i s one of the most common peptaibols and consists of 19 amino acids inc luding 8 alpha,alpha-dimethyl amino acid (aminoisobutylic acid, Aib) a nd phenylalaninol residues. Trichovirin I 4A consists of 13 amino acid s including 5 Aib residues and leucinol. In the synthesis of both, all couplings including those between sterically hindered Aib residues we re successfully achieved within 60 min using a newly developed couplin g agent, the CIP-additive. In the synthesis of trichovirin I 4A, no ra cemization was detected during the CIP-mediated coupling of peptide fr agments having an optically active alpha-amino acid at its C-terminus. The synthesis of 2 peptaibols shows that the CIP-additive method is e fficient not only for the coupling of sterically hindered amino acids but also for general fragment coupling. Copyright (C) 1996 Elsevier Sc ience Ltd