114376-47-5Relevant academic research and scientific papers
Phenysilane and Silicon Tetraacetate: Versatile Promotors for Amide Synthesis
Morisset, Eléonore,Chardon, Aurélien,Rouden, Jacques,Blanchet, Jér?me
supporting information, p. 388 - 392 (2020/01/24)
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.
Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
supporting information, p. 6949 - 6957 (2020/10/02)
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.
Oxidative functionalization of aliphatic and aromatic amino acid derivatives with H2O2 catalyzed by a nonheme imine based iron complex
Ticconi, Barbara,Colcerasa, Arianna,Di Stefano, Stefano,Lanzalunga, Osvaldo,Lapi, Andrea,Mazzonna, Marco,Olivo, Giorgio
, p. 19144 - 19151 (2018/05/31)
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.
Interception of amide ylides with sulfonamides: Synthesis of (: E)- N -sulfonyl amidines catalyzed by Zn(OTf)2
Chen, Jijun,Long, Wenhao,Fang, Shangwen,Yang, Yonggang,Wan, Xiaobing
supporting information, p. 13256 - 13259 (2017/12/26)
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.
Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models
Kubyshkin, Vladimir,Budisa, Nediljko
, p. 2452 - 2457 (2017/12/06)
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.
Conformational analysis and intramolecular interactions of l -proline methyl ester and its N -acetylated derivative through spectroscopic and theoretical studies
Braga, Carolyne B.,Ducati, Lucas C.,Tormena, Claudio F.,Rittner, Roberto
, p. 1748 - 1758 (2014/03/21)
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.
Tris(pentafluorophenyl)borane catalyzed acylation of alcohols, phenols, amines, and thiophenols under solvent-free condition
Prajapti, Santosh Kumar,Nagarsenkar, Atulya,Babu, Bathini Nagendra
, p. 1784 - 1787 (2014/03/21)
The acylation of alcohols, phenols, amines, and thiophenols was accomplished with 0.5 mol % of tris(pentafluorophenyl)borane [B(C 6F5)3] at ambient temperature under solvent-free condition. Major advantages of this method include high yield, short reaction time, simple procedure, compatibility with sensitive protecting groups as well as other functional groups, absence of racemization of optical active compounds, and epimerization of sugars.
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
Reddy, Damodara N.,Thirupathi, Ravula,Tumminakatti, Shama,Prabhakaran, Erode N.
supporting information; experimental part, p. 4413 - 4417 (2012/09/25)
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.
N → φ* Interaction and n)(φ pauli repulsion are antagonistic for protein stability
Jakobsche, Charles E.,Choudhary, Amit,Miller, Scott J.,Raines, Ronald T.
supporting information; experimental part, p. 6651 - 6653 (2010/07/04)
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.
Concurrent esterification and N-acetylation of amino acids with orthoesters: A useful reaction with interesting mechanistic implications
Gibson, Sarah,Romero, Dickie,Jacobs, Hollie K.,Gopalan, Aravamudan S.
scheme or table, p. 6737 - 6740 (2011/02/25)
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.
