Asymmetric enone epoxidation by short solid-phase bound peptides: Further evidence for catalyst helicity and catalytic activity of individual peptide strands

In the presence of short solid‐phase bound peptide catalysts, the Juliá–Colonna epoxidation of enones (such as chalcone) with hydrogen peroxide can be performed with high enantiomeric excess (≥95% ee). It was proposed earlier (A. Berkessel, N. Gasch, K. Glaubitz, C. Koch, Organic Letters, 2001, Vol. 3, pp. 3839–3842) that this remarkable catalysis is governed by the N‐terminus of individual and helical peptide strands. This mechanistic proposal was scrutinized further. (i) Nonaggregation of the peptide catalysts: five solid‐phase bound statistic mixtures (0/100; 30/70; 50/50; 70/30; 100/0) of D‐Leu and L‐Leu heptamers were generated and assayed as catalysts. A linear dependence of the epoxide ee on the enantiomeric composition of the catalysts resulted. (ii) Catalyst helicity [introduction of the helix‐stabilizing Cα–methyl‐L‐leucine, L‐(αMe)Leu]: solid‐phase bound Leu/(αMe)Leu‐pentamers of composition TentaGel–NH–[(αMe)‐L‐Leu]n–(L‐Leu)m–H (n = 0–4; m = 5–n) were prepared and assayed as catalysts. The introduction of up to two (αMe)‐L‐Leu residues (n = 1, 2) significantly enhanced the catalyst activity relative to the L‐Leu homopentamer (n = 0). Higher (αMe)‐L‐Leu contents (n = 3, 4) led to a decrease in both catalyst activity and enantiopurity of the product epoxide. In summary, both the individual catalytic action of the peptide strands and the helical conformation as the catalytically competent state of the peptide catalysts were further supported. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 90–96, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com