Peptide-catalyzed stereoselective Michael addition of aldehydes and ketones to heterocyclic nitroalkenes

Poláčková, Viera; Čmelová, Patrícia; Górová, Renáta; Šebesta, Radovan

doi:10.1007/s00706-017-2126-2

Cited by 6 publications

(3 citation statements)

References 58 publications

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“…Cationic side chains in proto-peptides could have facilitated important interactions with other proto-polymers, similar to their crucial role in today’s biology (70–72), that could have shaped the early stages of evolution (73). Moreover, cationic depsipeptides could have exhibited ligand binding and/or catalytic activities such as aldol condensation, Michael addition, and ester aminolysis (8, 74–79). For example, Adamala et al (76) showed that, when encapsulated within fatty acid vesicles, the dipeptide Ser−His catalyzed ester aminolysis to form a second, hydrophobic dipeptide.…”

Section: Discussionmentioning

confidence: 99%

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

Frenkel-Pinter

Haynes

Martin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

105

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Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine−linked, analogous to today’s proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein−RNA and protein−DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life.

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Section: Discussionmentioning

confidence: 99%

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

Frenkel-Pinter

Haynes

Martin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

105

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“…Peptide 1 is so robust that functional groups such as esters and acetals are tolerated [11–14] . Building on these findings we anticipated that an effective tripeptidic catalyst for conjugate addition reactions with substrates containing N ‐heterocyclic groups could be developed [10] …”

Section: Introductionmentioning

confidence: 98%

“…Despite intense research on this reaction, examples with N ‐heterocyclic substituted γ‐nitroaldehydes are seldom and mainly limited to 3‐pyridyl moieties [8, 9] . All reported examples require either high catalyst loadings (5–20 mol %), the use of protecting groups on the N ‐heterocycle, and/or suffer from low enantio‐ and diastereoselectivities [8–10] …”

Section: Introductionmentioning

confidence: 99%

Amine Catalysis with Substrates Bearing N‐Heterocyclic Moieties Enabled by Control over the Enamine Pyramidalization Direction

Möhler

Schnitzer

Wennemers

2020

Chemistry A European J

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Stereoselective organocatalytic C−C bond formations that tolerate N‐heterocycles are valuable since these moieties are common motifs in numerous chiral bioactive compounds. Such transformations are, however, challenging since N‐heterocyclic moieties can interfere with the catalytic reaction. Here, we present a peptide that catalyzes conjugate addition reactions between aldehydes and nitroolefins bearing a broad range of different N‐heterocyclic moieties with basic and/or H‐bonding sites in excellent yields and stereoselectivities. Tuning of the pyramidalization direction of the enamine intermediate enabled the high stereoselectivity.

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Stereoselective Aldol and Conjugate Addition Reactions Mediated by Proline‐Based Catalysts and Its Analogues: A Concise Review

2021

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The application of amino acids and small peptides as asymmetric organocatalysts in the aldol and conjugate addition reactions is a significant breakthrough in the past decade. The desired stereoselectivity in these reactions can be attained through tunable elements of diversity present in the amino acids/peptides. On this note, the current review highlights the organocatalytic aldol and conjugate addition by proline or its analogous in the form of amide/peptide derivatives. The wide‐ranging works of literature are classified based on the use of single amino acid or peptides as a catalyst. The designing of the aforementioned amide/amino acid/peptide catalyst, including their recent applications, is also detailed. Moreover, the analogous catalysts are also discussed, embedding other hetero‐organic functionalities that mimic the catalytic activity of proline in aldol/conjugate additions.

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Peptide-catalyzed stereoselective Michael addition of aldehydes and ketones to heterocyclic nitroalkenes

Cited by 6 publications

References 58 publications

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

Amine Catalysis with Substrates Bearing N‐Heterocyclic Moieties Enabled by Control over the Enamine Pyramidalization Direction

Stereoselective Aldol and Conjugate Addition Reactions Mediated by Proline‐Based Catalysts and Its Analogues: A Concise Review

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