Asymmetric enone epoxidation by short solid-phase bound peptides: further evidence for catalyst helicity and catalytic activity of individual peptide strands.
ABSTRACT 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 (> or = 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-(alphaMe)Leu]: solid-phase bound Leu/(alphaMe)Leu-pentamers of composition TentaGel-NH-[(alphaMe)-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 (alphaMe)-L-Leu residues (n = 1, 2) significantly enhanced the catalyst activity relative to the L-Leu homopentamer (n = 0). Higher (alphaMe)-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.
- Angewandte Chemie 05/2008; 120(20):3735-3737.
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ABSTRACT: Chiral epoxides serve as versatile building blocks in the synthesis of complex organic frameworks. The high strain imposed by the three-membered ring system makes epoxides prone to a variety of nucleophilic ring-opening reactions. Since the development of the Sharpless epoxidation, there have been many important contributions and advances in this area. With the rapid development of the field of asymmetric organocatalysis, a wide range of organocatalysts is now able to catalyze the epoxidation of broad class of unsaturated carbonyl compounds. In this Minireview, recent progress in the development of organocatalytic asymmetric epoxidation methods, the proposed mechanisms of these reactions and their applications as intermediates is reported.Angewandte Chemie International Edition in English 06/2014; · 13.45 Impact Factor
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ABSTRACT: Stapled helical l-leucine-based heptapeptides were synthesized and used as catalysts for the enantioselective epoxidation of α,β-unsaturated ketones. All N-terminal free stapled peptides were successfully used as chiral catalysts. Among them, the use of H-hS3,7hS-10 gave epoxide products with high enantioselectivities of up to 99% ee. Furthermore, the dominant conformations of the N-terminal protected stapled peptides R3,7R-10 and hS3,7hS-10 were investigated by 1H NMR, IR, CD spectra, and X-ray crystallographic analysis. The peptide R3,7R-10 formed a right-handed (P) α-helix in solution and in the crystalline state, while hS3,7hS-10 formed a right-handed (P) 310-helix in solution.Tetrahedron 08/2011; 67(34):6155-6165. · 2.82 Impact Factor