Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions Generating All‐Carbon Quaternary Stereogenic Centers

Kastl, Robert; Wennemers, Helma

doi:10.1002/anie.201301583

Cited by 118 publications

(67 citation statements)

References 84 publications

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“…[7][8][9] Tr ipeptides were developed that provide the products of aldol and conjugate addition reactions between aldehydes and nitroolefins in high yields as well as high enantio-and diastereoselectivities. [7][8][9] Tr ipeptides were developed that provide the products of aldol and conjugate addition reactions between aldehydes and nitroolefins in high yields as well as high enantio-and diastereoselectivities.…”

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confidence: 99%

“…Fore xample, while H-Pro-Pro-Asp-NH 2 is ap owerful catalyst for aldol reactions, [7] thec lose analogue H-dPro-Pro-Glu-NH 2 (1a) catalyzes conjugate addition reactions of aldehydes to nitroolefins and products of the competing homoaldol reaction do not form. [9] We therefore envisioned that tripeptides of the type H-Pro-Pro-Xaa would also allow for the identification of ac atalyst that accommodates the requirements for addition reactions of aldehydes to unprotected maleimides. [9] We therefore envisioned that tripeptides of the type H-Pro-Pro-Xaa would also allow for the identification of ac atalyst that accommodates the requirements for addition reactions of aldehydes to unprotected maleimides.…”

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Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide

2016

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The tripeptide H-dPro-Pro-Asn-NH 2 is presented as ac atalyst for asymmetric conjugate addition reactions of aldehydes to maleimide.T he peptidic catalyst promotes the reaction between various aldehydes and unprotected maleimide with high stereoselectivities and yields.T he obtained products were readily derivatized to the corresponding pyrrolidines,l actams,l actones,a nd peptide-like compounds. 1 HNMR spectroscopic,c rystallographic,a nd computational investigations provided insight into the conformational properties of H-dPro-Pro-Asn-NH 2 and revealed the importance of hydrogen bonding between the peptide and maleimide for catalyzing the stereoselective CÀCbond formation.

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Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide

2016

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“…We have introduced tripeptides of the type H‐Pro‐Pro‐Xaa as highly reactive and stereoselective catalysts for C–C bond forming reactions . For example, H‐Pro‐Pro‐Asp‐NH 2 is a very good catalyst for stereoselective aldol reactions, and H‐ d Pro‐Pro‐Asp‐NH 2 ( 1a ) as well as H‐ d Pro‐Pro‐Glu‐NH 2 ( 1b ) catalyze conjugate addition reactions of aldehydes to nitroethylene and β‐monosubstituted nitroolefins with excellent yields and stereoselectivities (Scheme ) .…”

Section: Introductionmentioning

confidence: 99%

“…The peptidic catalysts are so reactive that catalyst loadings of 1 mol% or less suffice to obtain the products for a large range of substrate combinations. The modular nature of H‐Pro‐Pro‐Xaa type catalysts even allowed for the development of peptidic catalyst H‐ d Pro‐Pro‐CH(Ph)CH 2 ( p ‐Me)C 6 H 4 ( 1c ) for addition reactions between aldehydes and β,β‐disubstituted nitroolefins, electrophiles that are significantly less inclined to engage in conjugate addition reactions and where homo‐aldol reactions are, therefore, pronounced side‐reactions when other amine‐based catalysts are used …”

Section: Introductionmentioning

confidence: 99%

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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“…10,11 There has been increasing interest in the synthesis of new GABA derivatives which can be potent drugs in the treatment of neurodegenerative disorders. 25 Although organocatalytic methods are versatile and valuable, 26 they are in this case dependant on application of excessive amounts of proline or peptide based catalysts (10-20% mol%) 24 and on the presence of usually chlorinated organic solvents, making their environmental impact high. [13][14][15] g-Nitroaldehydes can be obtained by two different Michaeltype additions: (i) from addition of aldehydes and a,b-unsaturated nitroalkenes and (ii) from addition of nitroalkanes and a,b-unsaturated aldehydes (Scheme 1a).…”

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Synthesis of γ-nitroaldehydes containing quaternary carbon in the α-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst

et al. 2014

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Synthesis of g-nitroaldehydes from branched chain aldehydes and a range of a,b-unsaturated nitroalkenes was achieved by a whole-cell biocatalytic reaction using 4-oxalocrotonate tautomerase as catalyst. Under mild conditions, cyclic and acyclic branched aldehydes were converted into synthetically valuable quaternary carbon containing g-nitroaldehydes. The yields of the desired products were influenced by reaction condition parameters such as organic solvent, temperature and pH. The whole-cell biocatalytic approach to the generation of a,a-substituted g-nitroaldehydes was compared to the organocatalytic approach involving the lithium salt of phenylalanine as a catalyst. As the resulting g-nitroaldehydes exhibited moderate antifungal activity and mild in vitro cytotoxicity against human fibroblasts (0.2-0.4 mM) they could further be examined as potentially useful pharmaceutical synthons.Scheme 2 Tautomerase based whole-cell catalyzed Michael addition of isobutanal to b-nitrostyrene. Fig. 1 Structures of (A) branched donors and (B) g-nitroaldehyde products of Michael-type additions catalyzed by 4-OT.This journal is

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Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions Generating All‐Carbon Quaternary Stereogenic Centers

Cited by 118 publications

References 84 publications

Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide

Peptide‐Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide

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

Synthesis of γ-nitroaldehydes containing quaternary carbon in the α-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst

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