Synthesis Of Dipeptides Research Articles

Rapid and efficient synthesis of the penta-peptide of elastin protein and peptides containing highly hindered α,α-dialkyl amino acids employing Fmoc-amino acid chlorides under microwave irradiation in solution phase

A rapid and efficient synthesis of peptides in solution employing Fmoc-amino acid chlorides under microwave irradiation is described. A comparison study of the microwave assisted method with those of conventional peptide synthesis using acid chlorides and various coupling additives has been performed. It has been found that, in general, the formation of a peptide bond, employing Fmoc-amino acid chloride and zinc dust or TBDMS-OBt under microwave irradiation is complete in 30-45 seconds with 90% yield of pure isolated peptide. Employing zinc dust as a coupling additive, the synthesis of several dipeptides, the pentapeptide fragment Fmoc- Val-Pro-Gly-Val-Gly-OBzl, of elastin and the difficult highly hindered couplings of α,α- dialkylamino acids are reported.

Synthesis of 4-Substituted-3-aminopiperidin-2-ones: Application to the Synthesis of a Conformationally Constrained TetrapeptideN-Acetyl-Ser-Asp-Lys-Pro

A new and practical synthetic strategy is developed for the synthesis of six-membered lactam-bridged dipeptides, 4-substituted-3-aminopiperidin-2-ones, featuring two key steps: (a) a diastereoselective addition of cuprate to (E)-alpha,beta-unsaturated ester (3) and (b) racemization-free reductive amination. On the basis of this methodology, conformationally constrained tetrapeptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) (2) has been successfully synthesized from 3-amino-4-vinylpiperidin-2-one (22).

Systematic Study of the Synthesis of Macrocyclic Dipeptide β-Turn Mimics Possessing 8-, 9-, and 10-Membered Rings by Ring-Closing Metathesis.

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionSystematic Study of the Synthesis of Macrocyclic Dipeptide β-Turn Mimics Possessing 8-, 9-, and 10-Membered Rings by Ring-Closing Metathesis.Ramesh Kaul, Simon Surprenant, and William D. LubellCite this: J. Org. Chem. 2005, 70, 12, 4901–4902Publication Date (Web):May 11, 2005Publication History Published online11 May 2005Published inissue 1 June 2005https://doi.org/10.1021/jo056027oCopyright © 2005 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views733Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (89 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Stereocontrolled synthesis of unnatural cyclic dipeptides containing an l-valine unit

Stereoselective synthesis of unusual nonproteinogenic dipeptides 7a, b, d, e and h and 13b and i, containing an l-valine unit and a cyclic unnatural α-amino acid, has been accomplished starting from the l-valine derived chiral synthon 1. The absolute configurations of the new stereocentres were assigned on the basis of 1H NMR spectra.

Study of the Effect of the Nature of the Side Chain in Esters of ?-Amino Acids on the Diastereoselectivity of Condensation with 5(4H)-Oxazolone in the Synthesis of Dipeptides with N-Terminal N-Acetylphenylalanine.

Conditions for fast racemization of 5(4H)-oxazolones prepared from N-acylphenylalanine were found. Reactions of 4-benzyl-2-methyl-5(4H)-oxazolone with amino acid esters proceed diastereoselectively to give predominantly dipeptides comprising R-phenylalanine. The diastereoselectivity increases with complication of the structure of the side chain in the amino acid esters.

Trypsin‐Catalyzed Kinetically Controlled Synthesis of a Precursor Dipeptide of Thymopentin in Organic Solvents, Using a Free Amino Acid as Nucleophile

Trypsin‐catalyzed, kinetically controlled synthesis of a precursor, dipeptide of thymopentin (TP‐5), Bz–Arg‐Lys–OH (or–OEt) in organic solvents was studied. Bz–Arg–OEt was used as the acyl donor and Lys–OH and Lys–OEt were used as the nucleophiles. Ethanol was selected as the organic solvent from ethanol, methanol, acetonitrile, and ethyl acetate tested under the experimental conditions. As expected, Lys–OEt is not a suitable nucleophile in trypsin‐catalyzed reaction, due to its competition with the protective Arg–OEt as acyl donor for the active site of trypsin, while Lys–OH does not have this problem. The optimal reaction condition for the synthesis of Bz–Arg‐Lys–OH was set up as 20% Tris‐HCl buffer, pH 8.0, 35°C for 6 h with the yield of 52.5%, or for 18–24 h with the yield of about 60%.

The synthesis of amides and dipeptides from unprotected amino acids by a simultaneous protection–activation strategy using boron trifluoride diethyl etherate

The reaction of l-phenylalanine ( 1 ) with boron trifluoride diethyl etherate and primary amines leads to the formation of amides via a cyclic boron intermediate. It is also possible to use the amino dicarboxylic acid l-aspartic acid and N-alkylated amino acids (peptoid building blocks, e.g., NPhe-OH 9 ). The latter can be used in the preparation of dipeptidomimetics.

Synthesis and evaluation of eight-membered cyclic pseudo-dipeptides

In the course of the development of calpain inhibitors, we report the synthesis of eight-membered cyclic pseudo dipeptides closely related to the known inhibitor SJA6017. The ring closure was effected by metathesis of the diallyl-substituted dipeptides 6 and 7. The formation of the dipeptides under kinetic control leads to the preferential formation of the unlike diastereomer 7 over the like diastereomer 6. The relative configuration of the diastereomers was determined by NMR and modeling studies of the related cyclic compounds 8 and 9 and their derivatives. The compounds proved not to inhibit calpain.

Synthesis and conformational properties of model dipeptides containing novel axially chiral α,β-didehydroamino acids at the ( i+1) position of a β-turn conformation

A series of model dipeptides containing some novel axially chiral α,β-didehydroamino acids at the ( i+1) position has been synthesised by reaction of the corresponding 4-(4-alkylcyclohexylidene)-2-phenyl-1,3-oxazol-5(4 H)-one with ( S)-phenylalanine cyclohexylamide. The conformations of two dipeptides in the crystal state have been studied by X-ray diffraction crystallographic analysis. The backbone torsion angles suggest that both peptides adopt similar type-II′ β-turn conformations. NMR spectroscopy has revealed that relatively rigid β-turn structures also persist in solution and that the absolute configurations of the axially chiral α,β-didehydroamino acids do not significantly influence the conformation of the peptide chain. Both heterochiral and homochiral dipeptides are found to accommodate the same βII′-turn conformation. Axially chiral α,β-didehydroamino acids ( R a )- and ( S a )-4-methyl-, 4-phenyl- and (4- tert-butylcyclohexylidene)glycine can be considered as elongated structural analogues of alanine, phenylglycine and tert-leucine of R and S configuration since, in these chiral α,β-didehydroamino acids, the methyl, phenyl and tert-butyl groups are located about 4.3 Å away from the peptide backbone in which they are incorporated.

Functionalized Cross-Linked Poly(vinyl alcohol) Resins as Reaction Scavengers and as Supports for Solid-Phase Organic Synthesis

New hydrophilic poly(vinyl alcohol) (PVA-OH) resins were prepared by an inverse suspension polymerization using epichlorohydrin as a cross-linker. These novel resins swell in a variety of solvents commonly used in solid-phase organic synthesis, such as dicholomethane, dioxane, methanol, tetrahydrofuran, and dimethylformamide. In addition, PVA-OH shows excellent swelling in water. The cross-linked PVA-OH beads were functionalized with an aldehyde group and were tested as scavengers for primary amines in three different reactions: amide bond formation, reductive amination reaction, and urea formation. With 1-2 equiv of the PVA aldehyde resin, all the excess primary amines were successfully scavenged. The utility of PVA-OH resins as solid supports in mono- and dipeptide synthesis was also investigated using symmetrical anhydride and MSNT/MeIm (2,4,6-mesitylenesulfonyl-3-nitro-1,2,4-triazolide in the presence of 1-methylimidazol) methods.

Study of the effect of the nature of the side chain in esters of -amino acids on the diastereoselectivity of condensation with 5(4H)-oxazolone in the synthesis of dipeptides with N-terminal N-acetylphenylalanine

Conditions for fast racemization of 5(4H)-oxazolones prepared from N-acylphenylalanine were found. Reactions of 4-benzyl-2-methyl-5(4H)-oxazolone with amino acid esters proceed diastereoselectively to give predominantly dipeptides comprising R-phenylalanine. The diastereoselectivity increases with complication of the structure of the side chain in the amino acid esters.

A peptidyl transferase ribozyme capable of combinatorial peptide synthesis

The formation of peptide bonds is a key step in both the chemical and biological synthesis of peptides. The ribozyme can use a wide range of amino acids as its substrate for the dipeptide synthesis. A library containing 29 peptides whose synthesis was catalyzed by this unique ribozyme was analyzed by mass spectrometry. These results implicate that ribozyme may have potential application in the peptide synthesis.

Synthesis and conformational studies of dipeptides constrained by disubstituted 3-(aminoethoxy)propionic acid linkers.

A series of cyclic compounds with dimethyl-substituted 3-(aminoethoxy)propionic acid linkers have been prepared as potential beta-turn mimics. The desired linkers were prepared from disubstituted pyrones, which were coupled with dipeptides and then subjected to macrocyclization using diethylcyanophosphonate to furnish cyclic compounds 1-5. Conformational analysis was carried out using NMR and X-ray crystallography. All of the five cyclic compounds were found to exist in type I or type II beta-turn conformations.

Modelling of the enzymatic synthesis of taste dipeptides with simultaneous extraction in a membrane phase contactor

The paper presents a model of the synthesis process of taste dipeptides carried out in a biphase water-organic phase system. An enzymatic conversion takes place within the aqueous phase where the enzyme is dissolved. The catalysis process is accompanied by the transport of reagents from/to the organic phase, which is a reservoir of hydrophobic reagents. The membrane contactor with a porous membrane holds the interface surface that serves as an interface area to the reactant mass transfer. The model was verified on the basis of the synthesis reaction of ZAlaPheOMe, a precursor of bitter dipeptide. The process was carried out in the ethyl acetate-polypropylene membrane-0.05 M Tris-HCl buffer system. Good agreement of experimental and model results was presented that enabled computer simulations of the process. That allowed us to choose the optimum parameters used in the batch and continuous process. The influence of interface surface area, phases volume and reagent concentrations on the process course, productivity and product purity was shown.

Horner–Wadsworth–Emmons reaction for the synthesis of unusual alpha,beta-didehydroamino acids with a chiral axis

The Horner-Wadsworth-Emmons reaction of N-benzyloxycarbonyl(dimethoxyphosphinyl) glycine esters with σ-symmetric prochiral 4-substituted-cyclohexanones under basic conditions is described. This reaction gives unusual α,β-didehydroamino acids with a chiral axis in their racemic form. The methodology has been extended to the synthesis of dipeptides containing a phenylalanine residue and these unusual new α,β-didehydroamino acids at the i+2 position.

Stereoselective Synthesis of Novel Dipeptide β‐Turn Mimetics Targeting Melanocortin Peptide Receptors.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Peptide Heterocycle Conjugates: A Diverted Edman Degradation Protocol for the Synthesis of N-Terminal 2-Iminohydantoins.

For Abstract see ChemInform Abstract in Full Text.

Peptide heterocycle conjugates: a diverted edman degradation protocol for the synthesis of N-terminal 2-iminohydantoins.

[reaction: see text] A modified Edman degradation procedure provides an effective means of introducing a heterocycle at the N-terminus of an alpha-amino acid amide or peptide. Reaction of a peptide with an isothiocyanate, followed by dehydrothiolative trapping of the intermediate thiourea, by intramolecular cyclization of the weakly nucleophilic adjacent amide nitrogen, generates an iminohydantoin. A solution-phase parallel synthesis of iminohydantoins and a polymer-supported synthesis of dipeptide- and tripeptide-derived iminohydantoins were also achieved.

Peptide syntheses mediated byBacillus subtilis protease

Bacillus subtilis protease (Amano protease N) was examined as a catalyst for peptide bond formationvia both the kinetically and thermodynamically controlled approaches. In general, the latter approach proved to be superior to the former, and a series of dipeptide syntheses and several segment condensations were achieved in good to high yields using the immobilized enzyme on Celite in acetonitrile with low water content.

Synthesis and conformational investigation of cyclic dipeptides: 7‐membered rings containing α‐ and β‐amino acids

The synthesis of heterocyclic compounds containing the 7-membered ring system [1,4]diazepane-2,5-dione is described. The aim of this study was to elaborate the solid phase and solution synthesis of eight representatives of the cyclic scaffold and to investigate their chemical stability and their conformational properties. The solid phase synthesis was performed on aminomethyl polystyrene resin using 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid as a backbone linker system (BAL-linker). After attachment of the alpha- and beta-amino acid and deprotection of the amino function, the dipeptide ester was obtained. The molecule was cyclized on the solid support by treatment with NaOMe in MeOH/NMP. The product was cleaved from the resin by TFA. For the solution pathway the linear dipeptides were synthesized by coupling of the BOC-protected L-alpha-amino acid with the beta2-amino acid ester (EDC/HOBT). After N- and C-terminal deprotection of the dipeptide, the linear species was cyclized with EDC/HOBT at a concentration of 3 mM in DMF. The products showed high chemical stability after storage in DMSO at room temperature for weeks. The x-ray and two dimensional NMR investigations were performed to investigate the conformation of the molecules. Three types of configuration could be distinguished by NMR, depending on the substitution pattern of the cyclic compounds. The x-ray results confirmed the NMR observations. In general the 7-membered rings showed rigidity, thus they could represent optimal scaffolds for new receptor ligands.