Jefferson D. Revell

Tripeptides as Efficient Asymmetric Catalysts for 1,4-Addition Reactions of Aldehydes to Nitroolefins–A Rational Approach†

Peptides have become increasingly popular as asymmetric catalysts for a range of reactions. Features such as facile synthesis, modularity, and often high selectivity and activity render peptidic catalysts attractive alternatives to metal-based catalysts and other organocatalysts. One of the largest challenges in the development of peptidic catalysts is the prediction and incorporation of desirable catalytic properties into a given peptide. This is already a challenge for small rigid organocatalysts, but even more so for short peptidic catalysts bearing many more degrees of rotational freedom. As a result, combinatorial chemistry has proven to be a valuable tool for the identification of peptidic catalysts. In this study we used insight gained from conformational analysis to guide the development of tripeptides as efficient asymmetric catalysts for conjugate addition reactions of aldehydes to nitroolefins. Recently, we introduced the peptide H-Pro-Pro-AspNH2 (1) as a catalyst for direct asymmetric aldol

Peptide Catalyzed Asymmetric Conjugate Addition Reactions of Aldehydes to Nitroethylene—A Convenient Entry into γ2-Amino Acids

The peptide H-D-Pro-Pro-Glu-NH2 is a highly effective catalyst for conjugate addition reactions between aldehydes and nitroethylene. Only 1 mol % of H-d-Pro-Pro-Glu-NH2 and a 1.5-fold excess of aldehyde with respect to nitroethylene suffice to obtain gamma-nitroaldehydes and, after reduction, monosubstituted gamma-nitroalcohols in excellent yields and optical purities. The products can be readily converted into gamma2-amino acids, thereby opening an effective direct entry into this important class of compounds.

New ionic liquid-modified silica gels as recyclable materials for L-proline- or H–Pro–Pro–Asp–NH2-catalyzed aldol reaction

L-proline and the tripeptide H–Pro–Pro–Asp–NH2 (1) have been supported, by adsorption, onto the surface of modified silica gels functionalized with a monolayer of covalently attached 1,2-dimethyl-imidazolium chloride, tetrafluoroborate or hexafluorophosphate ionic moieties, respectively. Three different linkers were used to attach the ionic liquid moiety to the surface of these supports. The resulting materials have been used as catalysts for the aldol reaction between acetone and several substituted benzaldehydes. Good yields and enantioselectivities, comparable to or better than those obtained under homogeneous conditions, were obtained. These materials are easily recovered by filtration, and studies regarding their re-use have been carried out. Studies performed using L-proline-supported materials have shown that the re-use of these materials is dependent on the nature of the linker. The supported tripeptide H–Pro–Pro–Asp–NH2 gave higher enantioselectivities than those obtained with supported-proline. Recycling investigations using tripeptide-supported materials showed continued good selectivities but diminishing conversions over consecutive runs. L-proline-supported materials however, can be used at least nine times without loss of either conversion or selectivity.

Separating stereoisomers of di‐, tri‐, and tetrapeptides using capillary electrophoresis with contactless conductivity detection

The separation and detection of small oligopeptides in CE with contactless conductivity detection were demonstrated. A strongly acidic separation buffer (0.5 M acetic acid) was employed in order to render the species cationic. Separation of the stereoisomers was achieved in typically 10-15 min by using either dimethyl-beta-CD (DM-beta-CD), (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (18C(6)H(4)), a combination of the two substances, or of histidine, as buffer additives. Calibration curves were determined for isomers of Gly-Asp and H-Pro-Asp-NH(2), in the range of 0.05-0.5 mM and 0.1-1 mM, respectively, and were found to be linear. LODs were determined to be in the order of 1.0 microM. The determination of isomeric impurities down to about 1% was found possible. Species showing good separation could also be successfully determined on an electrophoretic lab-on-chip device, with analysis times of a few minutes.

Identification of Catalysts in Combinatorial Libraries

Combinatorial methods allow for the generation of a large number of structurally similar yet unique compounds. For catalyst discovery using combinatorial libraries, the challenge lies in the development of screening methods that allow for the fast, reliable, and general identification of catalytically active library members. This article reviews methods that allow not only simultaneous testing of but also read-out of catalytic activity with parallel libraries and one-bead-one-compound libraries.