Introduction of the Aib-Pro unit into peptides by means of the ‘azirine/oxazolone method’ on solid phase

Abstract

A method for the direct introduction of Aib-Pro into peptides on solid phase was developed. The Aib-Pro unit was introduced by means of the ‘azirine/oxazolone method’ using allyl N-(2,2-dimethyl-2H-azirin-3-yl)-L-prolinate as the synthon. After the reaction of the resin-bound amino or peptide acid with allyl N-(2,2-dimethyl-2H-azirin-3-yl)-L-prolinate, the allyl protecting group of the resulting extended peptide could be removed by a mild Pd0-promoted procedure. Cleavage of the peptide from the resin was performed with UV light at 352 nm and yielded C-terminal protected peptides. The method found a successful application in the syntheses of different Aib-Pro containing peptaibol segments. Furthermore, a protected derivative of the peptide antibiotic Trichovirin I 1B was prepared by segment condensation.