103321-52-4Relevant articles and documents
Incorporation of CF3-pseudoprolines into peptides: A methodological study
Chaume, Gregory,Simon, Julien,Caupene, Caroline,Lensen, Nathalie,Miclet, Emeric,Brigaud, Thierry
, p. 10144 - 10153 (2013)
The peptide coupling reactions allowing the incorporation of trifluoromethyl substituted oxazolidine-type pseudoprolines (CF 3-ΨPro) into peptide chains have been studied. While standard protocols can be used for the peptide coupling reaction at the C-terminal position of the CF3-ΨPro, acid chloride activation has to be used for the peptide coupling reaction at the N-terminal position to overcome the decrease of nucleophilicity of the CF3-ΨPro. We demonstrate that the N-amidification of a diastereomeric mixture of CF3-ΨPro using Fmoc-protected amino acid chloride without base gave the corresponding dipeptides as a single diastereomer (6 examples). The ratio of the cis and trans amide bond conformers was determined by NMR study, highlighting the role of the Xaa side chains in the control of the peptide backbone conformation. Finally a tripeptide bearing a central CF3-ΨPro has been successfully synthesized.
Evaluating the Viability of Successive Ring-Expansions Based on Amino Acid and Hydroxyacid Side-Chain Insertion
Lawer, Aggie,Epton, Ryan G.,Stephens, Thomas C.,Palate, Kleopas Y.,Lodi, Mahendar,Marotte, Emilie,Lamb, Katie J.,Sangha, Jade K.,Lynam, Jason M.,Unsworth, William P.
, p. 12674 - 12683 (2020)
The outcome of ring-expansion reactions based on amino/hydroxyacid side-chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previous work on Successive Ring Expansion (SuRE) methods, details efforts to better define the scope and limitations of these reactions on lactam and β-ketoester ring systems with respect to ring size and additional functionality. The synthetic results provide clear guidelines as to which substrate classes are more likely to be successful and are supported by computational results, using a density functional theory (DFT) approach. Calculating the relative Gibbs free energies of the three isomeric species that are formed reversibly during ring expansion enables the viability of new synthetic reactions to be correctly predicted in most cases. The new synthetic and computational results are expected to support the design of new lactam- and β-ketoester-based ring-expansion reactions.
A Systematic Exploration of Macrocyclization in Apelin-13: Impact on Binding, Signaling, Stability, and Cardiovascular Effects
Tran, Kien,Murza, Alexandre,Sainsily, Xavier,Coquerel, David,C?té, Jér?me,Belleville, Karine,Haroune, Lounès,Longpré, Jean-Michel,Dumaine, Robert,Salvail, Dany,Lesur, Olivier,Auger-Messier, Mannix,Sarret, Philippe,Marsault, éric
, p. 2266 - 2277 (2018)
The apelin receptor generates increasing interest as a potential target across several cardiovascular indications. However, the short half-life of its cognate ligands, the apelin peptides, is a limiting factor for pharmacological use. In this study, we systematically explored each position of apelin-13 to find the best position to cyclize the peptide, with the goal to improve its stability while optimizing its binding affinity and signaling profile. Macrocyclic analogues showed a remarkably higher stability in rat plasma (half-life >3 h versus 24 min for Pyr-apelin-13), accompanied by improved affinity (analogue 15, Ki 0.15 nM and t1/2 6.8 h). Several compounds displayed higher inotropic effects ex vivo in the Langendorff isolated heart model in rats (analogues 13 and 15, maximum response at 0.003 nM versus 0.03 nM of apelin-13). In conclusion, this study provides stable and active compounds to better characterize the pharmacology of the apelinergic system.
Homochiral versus Heterochiral Trifluoromethylated Pseudoproline Containing Dipeptides: A Powerful Tool to Switch the Prolyl-Amide Bond Conformation
Chaume, Grégory,Simon, Julien,Lensen, Nathalie,Pytkowicz, Julien,Brigaud, Thierry,Miclet, Emeric
, p. 13602 - 13608 (2017)
The design of constrained peptides is of prime importance in the development of bioactive compounds and for applications in supramolecular chemistry. Due to its nature, the peptide bond undergoes a spontaneous cis-trans isomerism, and the cis isomers are much more difficult to stabilize than the trans forms. By using oxazolidine-based pseudoprolines (ψPro) substituted by a trifluoromethyl group, we show that the cis peptide bond can be readily switched from 0% to 100% in Xaa-ψPro dipeptides. Our results prove that changing the configuration of the Cα in Xaa or in ψPro is sufficient to invert the cis:trans populations while changing the nature of the Xaa side chain finely tuned the conformers ratio. Moreover, a strong correlation is found between the puckering of the oxazolidine ring and the peptide bond conformation. This finding highlights the role of the trifluoromethyl group in the stabilization of the peptide bond geometry. We anticipate that such templates will be very useful to constrain the backbone geometry of longer peptides.
Recyclable Merrifield resin-supported thiourea organocatalysts derived from l-proline for direct asymmetric aldol reaction
Li, Jia,Yang, Gengxu,Qin, Yanyan,Yang, Xinran,Cui, Yuanchen
, p. 613 - 618 (2011)
Four Merrifield resin-supported thiourea organocatalysts derived from l-proline were synthesized and found to be efficient catalysts for the direct asymmetric aldol reaction between ketone and aromatic aldehydes. The catalysts exhibited high catalytic activity, diastereoselectivity and excellent enantioselectivity at room temperature with a low loading (only 2 mol %). They also retained unchanged enantioselectivities even after being reused for at least four cycles.
Preparation of immobilized L-prolinamide via enzymatic polymerization of phenolic L-prolinamide and evaluation of its catalytic performance for direct asymmetric aldol reaction
Qu, Chengke,Zhao, Wenshan,Zhang, Lei,Cui, Yuanchen
, p. 209 - 213 (2014)
Phenolic L-prolinamide was allowed to participate in enzymatic polymerization with horseradish peroxidase as the catalyst, generating immobilized L-prolinamide. The catalytic performance of the resultant polymer-supported L-prolinamide for direct asymmetr
A highly efficient solvent-free asymmetric direct aldol reaction organocatalyzed by recoverable (S)-binam-L-prolinamides. ESI-MS evidence of the enamine-iminium formation
Guillena, Gabriela,Hita, Maria Del Carmen,Najera, Carmen,Viozquez, Santiago F.
, p. 5933 - 5943 (2008)
(Chemical Equation Presented) Recoverable (Sa)-binam-L- prolinamide in combination with benzoic acid is used as catalysts in the direct aldol reaction between cycloalkyl, alkyl, and α-functionalized ketones and aldehydes under solvent-free reac
Polymerization of L-proline functionalized styrene and its catalytic performance as a supported organocatalyst for direct enantioselective aldol reaction
Guo, Guozhang,Wu, Yufeng,Zhao, Xiaowei,Wang, Jing,Zhang, Lei,Cui, Yuanchen
, p. 740 - 746 (2016)
As an alternative approach to the graft modification of polymers to fabricate polymer-supported chiral organocatalysts in a bottom-up fashion, L-prolinamide functionalized polymers were prepared by general solution homopolymerization or copolymerization of L-proline functionalized styrene monomer in the presence of 1,4-divinylbenzene as the crosslinking agent. The catalytic performance of the as-prepared heterogeneous catalysts towards the direct enantioselective aldol reaction of ketones with a series of aromatic aldehydes was explored. Our findings indicate that the as-prepared heterogeneous catalysts can afford relevant aldol addition products with good yields (up to 96%), high diastereoselectivities (up to 8:92 dr) and excellent enantiomeric excess (up to 96%); they also exhibit good recyclability, retaining high yield and rate as well as good selectivity after several cycles.
Eco-friendly synthesis of peptides using fmoc-amino acid chlorides as coupling agent under biphasic condition
Kantharaju, Kamanna,Khatavi, Santosh Y.
, p. 699 - 707 (2021/08/23)
Background: Agro-waste derived solvent media act as a greener process for the peptide bond formation using Nα-Fmoc-amino acid chloride and amino acid ester salt with in situ neutralization and coupling under biphasic condition. The Fmoc-amino acid chlorides are prepared by the reported procedure of freshly distilled SOCl2 with dry CH2Cl2. The protocol found many added ad-vantages such as neutralization of amino acid ester salt and not required additional base for the neu-tralization, and directly coupling take place with Fmoc-amino acid chloride gave final product dipeptide ester in good to excellent yields. The protocol occurs with complete stereo chemical integrity of the configuration of substrates. Here, we revisited Schotten-Baumann condition, instead of using inorganic base. Objective: To develop green protocol for the synthesis of peptide bond using Fmoc-amino acid chloride with amino acid esters salt. Methods: The final product isolated is analyzed in several spectroscopic and analytical techniques such as FT-IR,1H-,13C-NMR, Mass spectrometry and RP-HPLC to check stereo integrity and puri-ty of the product. Conclusion: The present method developed greener using natural agro-waste (lemon fruit shell ash) derived solvent medium for the reaction and not required chemical entity.
DIMERS FOR USE IN SYNTHESIS OF PEPTIDOMIMETICS
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Paragraph 00322-00324, (2021/11/13)
Dimers for use in synthesis of peptidomimetics are described. Uses of dimers as synthons in synthesis of azapeptides and other peptidomimetics, azapeptides and other peptidomimetics synthesized from the dimers and uses of azapeptides and other peptidomimetics are also described.
