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.
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ABSTRACT: The hexapeptide Ser-Gly-Ala-Gly-Lys-Thr has been synthesized and characterized. It was designed as a minimal soluble peptide that would be likely to have the phosphate-binding properties observed in the P-loops of proteins that bind the β-phosphate of GTP or ATP. The β-phosphate in such proteins is bound by a combination of the side chain ε-amino group of the lysine residue plus the concavity formed by successive main chain peptide NH groups called a nest, which is favored by the glycines. The hexapeptide is shown to bind HPO(4) (2-) strongly at neutral pH. The affinities of the various ionized species of phosphate and hexapeptide are analyzed, showing that they increase with pH. It is likely the main chain NH groups of the hexapeptide bind phosphate in much the same way as the corresponding P-loop atoms bind the phosphate ligand in proteins. Most proteinaceous P-loops are situated at the N-termini of α-helices, and this observation has frequently been considered a key aspect of these binding sites. Such a hexapeptide in isolation seems unlikely to form an α-helix, an expectation in accord with the CD spectra examined; this suggests that being at the N-terminus of an α-helix is not essential for phosphate binding. An unexpected finding about the hexapeptide-HPO(4) (2-) complex is that the side chain ε-amino group of the lysine occurs in its deprotonated form, which appears to bind HPO(4) (2-) via an N···H-O-P hydrogen bond.Proteins Structure Function and Bioinformatics 01/2012; 80(5):1418-24. · 3.34 Impact Factor
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ABSTRACT: Catalytic enantioselective indole oxidation is a process of particular relevance to the chemistry of complex alkaloids, as it has been implicated in their biosynthesis. In the context of synthetic methodology, catalytic enantioselective indole oxidation allows a rapid and biomimetic entry into several classes of alkaloid natural products. Despite this potentially high utility in the total synthesis, reports of catalytic enantioselective indole oxidation remain sparse. Here we report a highly chemoselective catalytic system for the indole oxidation that delivers 3-hydroxy-indolenines with good chemical yields and moderate to high levels of enantio- and diastereoselectivity (up to 95:5 er and up to 92:8 dr). These results represent, to our knowledge, the most selective values yet reported in the literature for catalytic asymmetric indole oxidation. Furthermore, the utility of enantioenriched hydroxy-indolenines in stereospecific rearrangements is demonstrated.Journal of the American Chemical Society 06/2011; 133(23):9104-11. · 10.68 Impact Factor
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ABSTRACT: The development of peptide-based oxidation catalysts that use a transiently generated dioxirane as the chemically active species is reported. The active catalyst is a chiral trifluoromethyl ketone (Tfk) with a pendant carboxylic acid that can be readily incorporated into a peptide. These peptides were capable of epoxidizing alkenes in high yield (up to 89%) and enantiomeric ratios (er) ranging from 69.0:31.0 to 91.0:9.0, depending on the alkene substitution pattern.Organic Letters 02/2012; 14(4):1138-41. · 6.14 Impact Factor