Effect of γ-Substituted Proline Derivatives on the Performance of the Peptidic Catalyst H-dPro-Pro-Glu-NH₂

Dedicated to Professor Scott E. Denmark

Published as part of the Special Section dedicated to Scott E. Denmark on the occasion of his 65^th birthday

Abstract

Substituents at Cγ of proline are valuable probes to tune the trans/cis ratio of Xaa–Pro bonds. We investigated the effect of Cγ-substituents on the reactivity and stereoselectivity of the peptidic catalyst H-dPro-Pro-Glu-NH₂. Derivatives that bear electron-withdrawing and -donating substituents (OH, F, N₃, and SMe) at Cγ of the middle Pro-residue were examined. The results show that substituents at a 4R-configured Cγ hardly affect the stereoselectivity of the peptidic catalyst whereas substituents at a 4S-configured Cγ can be used to tune and improve the catalytic performance.

Key words

proline - peptides - trans/cis isomerization - organocatalysis - conjugate addition reactions

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