Solution Phase Synthesis of the 14-residue Peptaibol Antibiotic Trichovirin I

The 14-residue peptaibol antibiotic trichovirin I 4A of the structure Ac-Aib-L-Asn-L-Leu-Aib-L-Pro-L-Ala-L-Val-Aib-L-Pro-Aib-L-Leu-Aib-L-Pro-L-Leuol (Aib = alpha-aminoisobutyric acid, Leuol = leucinol) was synthesized by stepwise conventional solution phase synthesis using the Z/O tBu(OMe) strategy and HOBt/EDC as coupling reagents. Intermediates were fully characterized and the identity of the synthetic peptide with the component 4A of the natural, microheterogeneous peptide mixture was proven by electrospray mass spectrometry, HPLC, and bioassay.