Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Main Authors: Franziska Gille, Andreas Kirschning
• Format: Article
• Language: English
• Published: Beilstein-Institut 2016-03-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: catalysis; dehydroamino acids; Hartwig–Buchwald reaction; myxovalargin; peptides
• Online Access: https://doi.org/10.3762/bjoc.12.55

The preparation of peptide fragments containing dehydrovaline and dehydroisoleucine moieties present in the antibiotic myxovalargin is reported. Peptide formation is based on a copper-mediated C–N cross-coupling protocol between an acyl amide and a peptidic vinyl iodide. The presence of a neighboring arginine in the vinyl iodide posed a challenge with respect to the choice of the protecting group and the reaction conditions. It was found that ornithine – a suitable precursor – is better suited than arginine for achieving good yields for the C–N cross-coupling reaction. The optimized conditions were utilized for the synthesis of peptides 32, 33, 39 and 40 containing a neighboring ornithine as well as for the tripeptide 44 containing dehydroisoleucine with the correct stereochemistry.