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 Julia–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 C-alpha–methyl-L-leucine, L-(alpha-Me)Leu]: solid-phase bound Leu/(alpha-Me)Leu-pentamers of composition TentaGel–NH–[(alpha-Me)-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 (alpha-Me)-L-Leu residues (n = 1, 2) significantly enhanced the catalyst activity relative to the L-Leu homopentamer (n = 0). Higher (alpha-Me)-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.