Chapter 13. Peptides as Asymmetric Organocatalysts

Fingerhut, Anja; Grau, Dominik; Tsogoeva, Svetlana B.

doi:10.1039/9781782622093-00309

Cited by 10 publications

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“…In recent years more and more catalytically active peptides have been developed for different asymmetric reactions. − These catalysts are composed of amino acids, the building blocks of enzymes, but have molecular weights that are comparable to those of synthetic man-made catalysts. Several examples showed that peptidic catalysts can have impressive stereo-, chemo-, and regioselectivities, features that are hallmarks of enzymes. − Yet, peptidic catalysts often also have a broad substrate scope, a highly desirable feature of synthetic catalysts that is rarely observed for enzymes.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas several studies have explored the dependence of the reactivity and stereo-, chemo-, and regioselectivities of peptidic catalysts on their amino acid sequence, significantly less is known about their conformational features . In general, α-peptides of small or medium size (3–20 residues) are conformationally flexible and able to adopt several conformers that are in rapid equilibrium unless constraints are implemented .…”

Section: Introductionmentioning

confidence: 99%

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Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic Studies

et al. 2018

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Peptides have become valuable as catalysts for a variety of different reactions, but little is known about the conformational properties of peptidic catalysts. We investigated the conformation of the peptide H-dPro-Pro-Glu-NH, a highly reactive and stereoselective catalyst for conjugate addition reactions, and the corresponding enamine intermediate in solution by NMR spectroscopy and computational methods. The combination of nuclear Overhauser effects (NOEs), residual dipolar couplings (RDCs), J-couplings, and temperature coefficients revealed that the tripeptide adopts a single predominant conformation in its ground state. The structure is a type I β-turn, which gains stabilization from three hydrogen bonds that are cooperatively formed between all functional groups (secondary amine, carboxylic acid, amides) within the tripeptide. In contrast, the conformation of the enamine intermediate is significantly more flexible. The conformational ensemble of the enamine is still dominated by the β-turn, but the backbone and the side chain of the glutamic acid residue are more dynamic. The key to the switch between rigidity and flexibility of the peptidic catalyst is the COH group in the side chain of the glutamic acid residue, which acts as a lid that can open and close. As a result, the peptidic catalyst is able to adapt to the structural requirements of the intermediates and transition states of the catalytic cycle. These insights might explain the robustness and high reactivity of the peptidic catalyst, which exceeds that of other secondary amine-based organocatalysts. The data suggest that a balance between rigidity and flexibility, which is reminiscent of the dynamic nature of enzymes, is beneficial for peptidic catalysts and other synthetic catalysts.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic Studies

et al. 2018

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“…Unfortunately, only trace amounts of the product were detected by TLC and increasing the reaction time did not improve the yield. Although DMSO is commonly used for studies on aldol reactions involving acyclic ketones, 35,36 studies have shown that acyclic ketones may be poor substrates in DMSO. 37,38 This indicates inefficient formation of active enamine intermediates by acyclic ketones.…”

Section: Peptide Synthesismentioning

confidence: 99%

Development of fructose-1,6-bisphosphate aldolase enzyme peptide mimics as biocatalysts in direct asymmetric aldol reactions

et al. 2021

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“…In this context, several representative organocatalysts present two or more functional groups that act in cooperative or bifunctional strategies [12][13][14][15][16][17][18]. Several research groups have used natural and unnatural amino acids and peptides [19][20][21][22][23][24][25][26][27][28][29][30][31], chiral ureas and thioureas [32][33][34][35][36][37][38][39][40], and chiral amides [41][42][43][44][45] as building blocks or templates in organocatalyst design. In this context, a significant number of (S)-proline derivatives have been developed while searching for an improvement in the catalytic efficiency and stereoselectivity [46][47][48][49][50][51][52][53].…”

Section: Introductionmentioning

confidence: 99%

New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction

et al. 2020

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Novel organocatalytic systems based on the recently developed (S)-proline derivative (2S)-[5-(benzylthio)-4-phenyl-(1,2,4-triazol)-3-yl]-pyrrolidine supported on mesoporous silica were prepared and their efficiency was assessed in the asymmetric aldol reaction. These materials were fully characterized by FT-IR, MS, XRD, and SEM microscopy, gathering relevant information regarding composition, morphology, and organocatalyst distribution in the doped silica. Careful optimization of the reaction conditions required for their application as catalysts in asymmetric aldol reactions between ketones and aldehydes afforded the anticipated aldol products with excellent yields and moderate diastereo- and enantioselectivities. The recommended experimental protocol is simple, fast, and efficient providing the enantioenriched aldol product, usually without the need of a special work-up or purification protocol. This approach constitutes a remarkable improvement in the field of heterogeneous (S)-proline-based organocatalysis; in particular, the solid-phase silica-bonded catalytic systems described herein allow for a substantial reduction in solvent usage. Furthermore, the supported system described here can be recovered, reactivated, and reused several times with limited loss in catalytic efficiency relative to freshly synthesized organocatalysts.

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Chapter 13. Peptides as Asymmetric Organocatalysts

Cited by 10 publications

References 0 publications

Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic Studies

Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic Studies

Development of fructose-1,6-bisphosphate aldolase enzyme peptide mimics as biocatalysts in direct asymmetric aldol reactions

New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction

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