Asymmetric catalysis with short-chain peptides

Lewandowski, Bartosz; Wennemers, Helma

doi:10.1016/j.cbpa.2014.09.011

Cited by 69 publications

(42 citation statements)

References 45 publications

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“…Peptide-based catalysis has also proven to be an effective strategy for the synthesis of optically enriched compounds. 2 Detailed analyses of structural trends in proteins, 3 as well as physical organic studies of oligopeptides in organic solution, 4 have enabled the design of specific peptide secondary structures with high precision. Nonetheless, the many bond rotations available to short peptides provides the possibility that these peptidic catalysts may exist as an equilibrial mixture of conformers under the reaction conditions, both in low energy ground states and in competing transition states.…”

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confidence: 99%

Structural studies of β-turn-containing peptide catalysts for atroposelective quinazolinone bromination

et al. 2016

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We describe herein a crystallographic and NMR study of the secondary structural attributes of a β-turn-containing tetra-peptide, Boc-Dmaa-D-Pro-Acpc-Leu-NMe2, which was recently reported as a highly effective catalyst in the atroposelective bromination of 3-arylquinazolin-4(3H)-ones. Inquiries pertaining to the functional consequences of residue substitutions led to the discovery of a more selective catalyst, Boc-Dmaa-D-Pro-Acpc-Leu-OMe, the structure of which was also explored. This new lead catalyst was found to exhibit a type I’ β-turn secondary structure both in the solid state and in solution, a structure that was shown to be an accessible conformation of the previously reported catalyst, as well.

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confidence: 99%

Structural studies of β-turn-containing peptide catalysts for atroposelective quinazolinone bromination

et al. 2016

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“…We chose synthetic oligopeptides as catalysts [11] as these should be well-suited for binding the amino acid derived intermediates,a sd emonstrated for such platforms in acyl transfer reactions. [12] Incorporation of catalytically active pmethylhistidine (Pmh) in ad ual role as Lewis base for the acetyl transfer (Scheme 2) and as Brønsted base in the decarboxylative protonation (Scheme 2) may allow performing the entire reaction by employing as ingle catalyst.…”

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confidence: 99%

The Enantioselective Dakin–West Reaction

et al. 2016

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Here we report the development of the first enantioselective Dakin-West reaction, yielding a-acetamido methylketones with up to 58 %eewith good yields.T wo of the obtained products were recrystallized once to achieve up to 84 %ee. The employed methylimidazole-containing oligopeptides catalyze both the acetylation of the azlactone intermediate and the terminal enantioselective decarboxylative protonation. We propose ad ispersion-controlled reaction path that determines the asymmetric reprotonation of the intermediate enolate after the decarboxylation.Even though the Dakin-West (DW) reaction dates back to 1928, [1] it is still one of the most effective synthetic procedures to prepare a-acylamido ketones from primary a-amino acids. [2] Generally,t he treatment of an amino acid with an acid anhydride and base,t ypically pyridine,a te levated temperature provides the desired product upon liberation of CO 2 (Scheme 1). Numerous modifications of the original reaction conditions were developed, [2] including catalytic variants, [3] broadening its scope and applicability.U nsurprisingly,the DW reaction found application in the preparation of a-acylamido ketones as valuable precursors for various biologically active compounds, [4] and even in Woodwards fundamental total synthesis of strychnine. [5] Remarkably,n o asymmetric variant has been developed to date,thus restricting the use of this important reaction in modern synthetic chemistry.

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“…Such a combination of rigidity, paired with a certain degree of conformational flexibility, is key to the catalytic performance of numerous enzymes . The presented data suggests that a similar combination of rigidity and flexibility may also be key to the catalytic performance of H‐Pro‐Pro‐Xaa type peptides . We are currently performing detailed solution‐phase conformational studies to explore this hypothesis further.…”

Section: Discussionmentioning

confidence: 81%

Crystal structures of peptidic catalysts of the H‐dPro‐Pro‐Xaa type

et al. 2017

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Crystal structures of catalytically active tripeptides of the general type H-dPro-Pro-Xaa and related N-acetylated analogs were compared. The influence of acylation at the N-terminus, the nature of the C-terminal residue, coordinating groups, and intramolecular hydrogen bonds on the conformation of the tripeptides was examined. Regardless of the presence or absence of stabilizing intramolecular H-bonds or n → π* interactions, all of the analyzed peptides share a β-turn-like conformation, which highlights the structural rigidity of the dPro-Pro motif and its value for conformational preorganization. The C-terminal residues and coordinating moieties were found to affect the turn-conformation, which suggests that H-dPro-Pro-Xaa type peptides are sufficiently flexible to adopt distinctly different but related conformations.

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Asymmetric catalysis with short-chain peptides

Cited by 69 publications

References 45 publications

Structural studies of β-turn-containing peptide catalysts for atroposelective quinazolinone bromination

Structural studies of β-turn-containing peptide catalysts for atroposelective quinazolinone bromination

The Enantioselective Dakin–West Reaction

Crystal structures of peptidic catalysts of the H‐dPro‐Pro‐Xaa type

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