Hydrocarbon stapling has attracted increased attention recently because of their potential application as functionalized short peptides for the study of medicinal chemistry. Accordingly, we attempted at synthesis of hydrocarbon-stapled short peptides possessing L-proline at the N-terminus. We demonstrated the synthesis of i,i+1 hydrocarbon stapled peptide using cis-4-hydroxyl-L-proline and the synthesis of i,i+3 hydrocarbon stapled peptide using (R)-α-allyl-proline. Moderate E or Z -selectivities were observed for the ring-closing metathesis reaction. These hydrocarbon-stapled oligopeptides were subjected to Michael addition reaction of 1-methylindole to α,β-unsaturated aldehyde. The introduction of the side-chain stapling improved the catalytic activity of peptide organocatalyst in the Michael addition reaction. CD spectra of these peptides also suggested that the catalytic activities were proportional to intensities of right-handed helices, which were enhanced by the side-chain stapling.

Synthesis of helical hydrocarbon-stapled oligopeptides using L-proline at the N-terminus

ACS Spring Meeting 2021

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