- Phenysilane and Silicon Tetraacetate: Versatile Promotors for Amide Synthesis
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Phenylsilane was reevaluated as a useful coupling reagent for amide synthesis. At room temperature, a wide range of amides and peptides were obtained in good to excellent yields (up to 99 %). For the first time, Weinreb amides synthesis mediated by a hydrosilane were also documented. Comparative experiments with various acetoxysilanes suggested the involvement of a phenyl-triacyloxysilane. From this mechanistic study, silicon tetraacetate was shown as an efficient amine acylating agent.
- Morisset, Eléonore,Chardon, Aurélien,Rouden, Jacques,Blanchet, Jér?me
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supporting information
p. 388 - 392
(2020/01/24)
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- Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
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Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.
- Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
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supporting information
p. 6949 - 6957
(2020/10/02)
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- Oxidative functionalization of aliphatic and aromatic amino acid derivatives with H2O2 catalyzed by a nonheme imine based iron complex
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The oxidation of a series of N-acetyl amino acid methyl esters with H2O2 catalyzed by a very simple iminopyridine iron(ii) complex 1 easily obtainable in situ by self-assembly of 2-picolylaldehyde, 2-picolylamine, and Fe(OTf)2 was investigated. Oxidation of protected aliphatic amino acids occurs at the α-C-H bond exclusively (N-AcAlaOMe) or in competition with the side-chain functionalization (N-AcValOMe and N-AcLeuOMe). N-AcProOMe is smoothly and cleanly oxidized with high regioselectivity affording exclusively C-5 oxidation products. Remarkably, complex 1 is also able to catalyze the oxidation of the aromatic N-AcPheOMe. A marked preference for the aromatic ring hydroxylation over Cα-H and benzylic C-H oxidation was observed, leading to the clean formation of tyrosine and its phenolic isomers.
- Ticconi, Barbara,Colcerasa, Arianna,Di Stefano, Stefano,Lanzalunga, Osvaldo,Lapi, Andrea,Mazzonna, Marco,Olivo, Giorgio
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p. 19144 - 19151
(2018/05/31)
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- Interception of amide ylides with sulfonamides: Synthesis of (: E)- N -sulfonyl amidines catalyzed by Zn(OTf)2
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Through the interception of amide ylides with sulfonamides, we herein report the first general example of an intermolecular condensation reaction between sulfonamides and amides. Beyond formamides, this approach was successfully applied to a variety of lactams and linear amides, giving rise to a broad array of (E)-N-sulfonyl amidines.
- Chen, Jijun,Long, Wenhao,Fang, Shangwen,Yang, Yonggang,Wan, Xiaobing
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supporting information
p. 13256 - 13259
(2017/12/26)
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- Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models
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Fluorinated moieties are highly valuable to chemists due to the sensitive NMR detectability of the 19F nucleus. Fluorination of molecular scaffolds can also selectively influence a molecule's polarity, conformational preferences and chemical reactivity, properties that can be exploited for various chemical applications. A powerful route for incorporating fluorine atoms in biomolecules is last-stage fluorination of peptide scaffolds. One of these methods involves esterification of the C-terminus of peptides using a diazomethane species. Here, we provide an investigation of the physicochemical consequences of peptide esterification with partially fluorinated ethyl groups. Derivatives of N-acetylproline are used to model the effects of fluorination on the lipophilicity, hydrolytic stability and on conformational properties. The conformational impact of the 2,2-difluoromethyl ester on several neutral and charged oligopeptides was also investigated. Our results demonstrate that partially fluorinated esters undergo variable hydrolysis in biologically relevant buffers. The hydrolytic stability can be tailored over a broad pH range by varying the number of fluorine atoms in the ester moiety or by introducing adjacent charges in the peptide sequence.
- Kubyshkin, Vladimir,Budisa, Nediljko
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p. 2452 - 2457
(2017/12/06)
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- Conformational analysis and intramolecular interactions of l -proline methyl ester and its N -acetylated derivative through spectroscopic and theoretical studies
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This work reports a detailed study regarding the conformational preferences of l-proline methyl ester (ProOMe) and its N-acetylated derivative (AcProOMe) to elucidate the effects that rule their behaviors, through nuclear magnetic resonance (NMR) and infrared (IR) spectroscopies combined with theoretical calculations. These compounds do not present a zwitterionic form in solution, simulating properly amino acid residues in biological media, in a way closer than amino acids in the gas phase. Experimental 3JHH coupling constants and infrared data showed excellent agreement with theoretical calculations, indicating no variations in conformer populations on changing solvents. Natural bond orbital (NBO) results showed that hyperconjugative interactions are responsible for the higher stability of the most populated conformer of ProOMe, whereas for AcProOMe both hyperconjugative and steric effects rule its conformational equilibrium.
- Braga, Carolyne B.,Ducati, Lucas C.,Tormena, Claudio F.,Rittner, Roberto
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p. 1748 - 1758
(2014/03/21)
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- A method for stabilizing the cis prolyl peptide bond: Influence of an unusual n→π* interaction in 1,3-oxazine and 1,3-thiazine containing peptidomimetics
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The cis/trans isomer ratios of the Xaa-Pyr (Pyr = pyrrolidine) 3° amide bonds are significantly high (~90% cis) in the novel peptidomimetics where Pyr contains 1,3-oxazine (Oxa) or 1,3-thiazine (Thi) at its 2 position. We find that an unusual n→πi-1* interaction, selectively stabilizes the cis conformer and the n)(n repulsion destabilizes the trans conformer of these molecules. Both these electronic effects oppose the steric effects in the 3° amide bond. The structural requirements for manifestation of these electronic effects are determined.
- Reddy, Damodara N.,Thirupathi, Ravula,Tumminakatti, Shama,Prabhakaran, Erode N.
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supporting information; experimental part
p. 4413 - 4417
(2012/09/25)
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- Peptide-Based Beta Turn Mimetics
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Beta-mimetic compositions and methods of making and using such compositions in preparing bioactive peptides, such as antimicrobial peptides, are disclosed. In particular, spirocyclic proline hybrids are provided that may be used to alter the cis/trans isomerization of proline in a peptide, and which may replace a residue, for example, the i+2 residue, of a beta-turn in a peptide of known sequence, thereby retaining or modifying the structure of the peptide.
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- Concurrent esterification and N-acetylation of amino acids with orthoesters: A useful reaction with interesting mechanistic implications
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The concurrent esterification and N-acetylation of amino acids has been studied with triethyl orthoacetate (TEOA) and triethyl orthoformate (TEOF). In a surprising finding, only 1 equiv of TEOA in refluxing toluene was necessary to convert l-proline and l-phenylalanine into the corresponding N-acetyl ethyl esters in good yield. The same transformation using TEOF was not effective. Stereochemical outcome and stoichiometric studies as well as structural variation of the amino acids in this reaction provided unexpected mechanistic insight.
- Gibson, Sarah,Romero, Dickie,Jacobs, Hollie K.,Gopalan, Aravamudan S.
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scheme or table
p. 6737 - 6740
(2011/02/25)
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- N → φ* Interaction and n)(φ pauli repulsion are antagonistic for protein stability
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In many common protein secondary structures, such as α-, 3 10, and polyproline II helices, an n → φ* interaction places the adjacent backbone amide carbonyl groups in close proximity to each other. This interaction, which is reminiscent of the Buergi-Dunitz trajectory, involves delocalization of the lone pairs (n) of the oxygen (O i-1) of a peptide bond over the antibonding orbital (-*) of CiOi of the subsequent peptide bond. Such a proximal arrangement of the amide carbonyl groups should be opposed by the Pauli repulsion between the lone pairs (n) of Oi-1 and the bonding orbital (-) of CiOi. We explored the conformational effects of this Pauli repulsion by employing common peptidomimetics, wherein the n → -*interaction is attenuated while the Pauli repulsion is retained. Our results indicate that this Pauli repulsion prevents the attainment of such proximal arrangement of the carbonyl groups in the absence of the n → φ* interaction. This finding indicates that the poor mimicry of the amide bond by many peptidomimetics stems from their inability to partake in the n → φ* interaction and emphasizes the quantum-mechanical nature of the interaction between adjacent amide carbonyl groups in proteins.
- Jakobsche, Charles E.,Choudhary, Amit,Miller, Scott J.,Raines, Ronald T.
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supporting information; experimental part
p. 6651 - 6653
(2010/07/04)
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- Proline-rich proteins - Deriving a basis for residue-based selectivity in polyphenolic binding
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1H NMR titration experiments have been used to establish that minimal proline-based models show enhanced binding selectivity towards phenol in CDCl3, relative to other similarly protected amino acid residues. Cooperative binding effects appear to play a role, with sarcosine models affording binding constants to phenol intermediate to those obtained from proline models and other amino acid models. The mechanism for binding, based on DFT calculations and the application of Hunter's molecular recognition toolbox model, cannot be solely attributed to hydrogen bond strength, and appears to be mediated through C-H-π bonds and the rotational freedom of the amide substrate. The Royal Society of Chemistry 2008.
- Croft,Foley
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supporting information; experimental part
p. 1594 - 1600
(2008/10/09)
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- Aldehyde-based racemization in the dynamic kinetic resolution of N-heterocyclic α-amino esters using Candida antarctica lipase A
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The present research introduces approaches for the dynamic kinetic resolution of the methyl esters of proline and pipecolic acid. As the result, a method was developed which is based on the acylation of the secondary amino group of the amino esters with vinyl butanoate by Candida antarctica lipase A. In the optimized method, acetaldehyde as a racemizing agent is released in situ from vinyl butanoate in the presence of triethylamine, allowing ca. 90% of the racemic proline and 70% of the pipecolic acid methyl esters to be acylated in the forms of highly enantiopure (ee=97%) butanamides with the S-absolute configurations.
- Liljeblad, Arto,Kiviniemi, Anu,Kanerva, Liisa T.
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p. 671 - 677
(2007/10/03)
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- Anodic modification of proline derivatives using a lithium perchlorate/nitromethane electrolyte solution.
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[reaction: see text] N-Acyliminium cation of prolines was efficiently generated to accumulate in an undivided cell at 0 degrees C by an anodic oxidation of N-acylprolines or alpha'-phenylsulfanylated N-acylproline derivatives in a lithium perchlorate/nitr
- Kim, Shokaku,Hayashi, Kanako,Kitano, Yoshikazu,Tada, Masahiro,Chiba, Kazuhiro
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p. 3735 - 3737
(2007/10/03)
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- Catalytic asymmetric hydrogenation of 1-aza-2-cycloalkene-2-carboxylates catalyzed by a trans-chelating chiral diphosphine PhTRAP-rhodium complex
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A rhodium complex coordinated with a trans-chelating chiral diphosphine (S,S)-(R,R)-PhTRAP was an effective catalyst for asymmetric hydrogenation of N-acyl-1-aza-2-cycloalkene-2-carboxylates, which gave the corresponding protected cyclic α-amino acids wit
- Kuwano, Ryoichi,Karube, Daisuke,Ito, Yoshihiko
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p. 9045 - 9049
(2007/10/03)
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- Electron transfer through the hydrogen-bonded interface of a β-turn- forming depsipeptide
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Hydrogen-bonding networks are believed to play an important role in electron-transfer pathways in a protein medium. A porphyrin-quinone donor- acceptor compound with a depsipeptide bridge which forms a β-turn has been synthesized to study hydrogen bond-mediated electron transfer. The placement of the donor and acceptor has been chosen to favor electron transfer through the hydrogen bond interface of the β-turn. Use of ester linkages also allows control of the hydrogen-bonding pattern within the β-turn-forming depsipeptide. Infrared spectroscopy in the amide A (NH stretch) and amide I (carbonyl stretch) regions indicates that the β-turn conformation is about 85% populated in dichloromethane and essentially completely disrupted in dimethyl sulfoxide at 296 K. The electron-transfer rate constant, k(et), was evaluated using the singlet excited-state lifetimes of the porphyrin in the presence and absence of an electron acceptor. The lifetimes were obtained using time-correlated single-photon-counting fluorescence spectroscopy. Very fast electron transfer (k(et) = (1.1 ± 0.1) x 109 s-1) was observed in the presence of the β-turn conformation. When the β-turn structure was disrupted using the solvent DMSO, electron transfer was no longer competitive with the intrinsic fluorescence emission. Analysis of the data in terms of Marcus theory and the pathway model for electronic coupling yielded a value for the hydrogen bond coupling decay factor, ε(hb), of 0.8 ± 0.4, which is of the same order of magnitude as the theoretically predicted value of 0.36.
- Williamson, David A.,Bowler, Bruce E.
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p. 10902 - 10911
(2007/10/03)
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- An asymmetric approach to the pyrrolizidine ring system via N-acetyl and N-propionyl anion cyclisation processes
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An efficient route to the pyrrolizidine ring system has been developed. The method, which uses N-acetyl and N-propionyl anion cyclisation reactions as the key steps has provided the natural pyrrolizidines (-)-(1R, 8S)-1-hydroxypyrrolizidine (10), (-)-pyrrolizidin-1-ene-3-one (13), (±)-trachelanthamidine (18) together with a range of 2-methyl substituted pyrrolizidine-3-ones.
- Murray,Murray, Anthony,Proctor,Proctor, George R.,Murray,Murray, P. John
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p. 291 - 294
(2007/10/02)
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- Synthesis of specially stable-isotope-labeled L-proline via L-glutamic acid
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(3,4-(13)C2)-L-proline and ((15)N)-L-proline were prepared from the correspondingly labeled L-glutamic acids via a single scheme in high yield and on a gram scale.The synthetic route is based on the ring closure of L-glutamic acid to L-5-oxoproline and the selective reduction of the 5-amide function, without interference with the 2-carboxylate function and the asymmetric center.The selective reduction is effected by first converting the amide into the corresponding thioamide and subsequently reducing the thioamide to the amine using tributyltin hydride, in combination with protection and deprotection steps.In earlier work we described the preparation of L-glutamic acid isotopically labeled at any position or combination of positions starting from simple highly enriched synthons.The synthetic scheme in this publication makes L-proline, (13)C- or (15)N-labeled at any position or combination of positions, easily available.The labeled L-prolines are charcterized by (1)H-, (13)C- and (15)N-NMR and mass spectrometry.
- Cappon, J. J.,Walle, G. A. M. van der,Verdegem, P. J. E.,Raap, J.,Lugtenburg, J.
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p. 517 - 523
(2007/10/02)
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- Chemoenzymatic synthesis of specifically stable-isotope labelled L-glutamic acid, L-glutamine and L-proline
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A synthetic scheme has been developed for the preparation of 13C- or 15N-enriched 2-oxoglutaric acid (1), L-glutamic acid (2), L-glutamine (3) and L-proline (4), from simple and commercially available highly enriched synthons.The products have been obtained with high isotope enrichment (>98percent) and high optical purity on a gram scale.The scheme allows the specific labelling of every C- or N-position and any combination of positions.The used combination of organic synthetic steps and enzymatic steps proves to be a very efficient way to obtain optically active biomolecules.
- Cappon, J J,Baart, J,Walle, G A M van der,Verdegem, P J E,Raap, J,Lugtenburg
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p. 813 - 816
(2007/10/02)
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- Syntheses of Substituted L- and D-Tryptophans
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Several 5-substituted nb-methoxycarbonyl-L- and -D-tryptophan derivatives were synthesized from proline by a new route involving electrochemical oxidation, as well as by the known procedures.Removal of the Nb-methoxycarbonyl group was accomplished by treatment with Me3SiI in refluxing chloroform, then alkaline hydrolysis of the methyl esters afforded 5-substituted L- and D-tryptophans with high optical purities.Keywords - L-tryptophan 5-substituted; D-tryptophan 5-substituted; anodic oxidation; N-methoxycarbonyl group deprotection; Fischer indole synthesis; iodotrimethylsilane
- Irie, Kunihiko,Ishida, Akihiko,Nakamura, Tohru,Oh-ishi, Tokuro
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p. 2126 - 2139
(2007/10/02)
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