- Generation of Oxyphosphonium Ions by Photoredox/Cobaloxime Catalysis for Scalable Amide and Peptide Synthesis in Batch and Continuous-Flow
-
Phosphine-mediated deoxygenative nucleophilic substitutions, such as the Mitsunobu reaction, are of great importance in organic synthesis. However, the conventional protocols require stoichiometric oxidants to trigger the formation of the oxyphosphonium i
- Chen, Xiangyang,Houk, Kendall N.,Mo, Jia-Nan,Su, Junqi,Umanzor, Alexander,Zhang, Zheng,Zhao, Jiannan
-
supporting information
(2022/01/06)
-
- Synthesis of Dipeptide, Amide, and Ester without Racemization by Oxalyl Chloride and Catalytic Triphenylphosphine Oxide
-
An efficient triphenylphosphine oxide-catalyzed amidation and esterification for the rapid synthesis of a series of dipeptides, amides, and esters is described. This reaction is applicable to challenging couplings of hindered carboxylic acids with weakly
- Ren, Ji-Wei,Tong, Meng-Nan,Zhao, Yu-Fen,Ni, Feng
-
supporting information
p. 7497 - 7502
(2021/10/12)
-
- Engineered Substrate for Cyclooxygenase-2: A Pentapeptide Isoconformational to Arachidonic Acid for Managing Inflammation
-
Beyond the conventional mode of working of anti-inflammatory agents through enzyme inhibition, herein, COX-2 was provided with an alternate substrate. A proline-centered pentapeptide isoconformational to arachidonic acid, which exhibited appreciable selectivity for COX-2, overcoming acetic acid- and formalin-induced pain in rats to almost 80%, was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tripeptides that ensured the safe breakdown of the peptide under in vivo conditions. The kinetic parameter Kcat/Km for COX-2-mediated metabolism of the peptide (6.3 × 105 M-1 s-1) was quite similar to 9.5 × 105 M-1 s-1 for arachidonic acid. Evidenced by the molecular dynamic studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably been taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.
- Kaur, Baljit,Kaur, Manpreet,Kaur, Navjot,Garg, Saweta,Bhatti, Rajbir,Singh, Palwinder
-
p. 6363 - 6376
(2019/07/08)
-
- 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Toluene-4-sulfonate (DMT/NMM/TsO?) Universal Coupling Reagent for Synthesis in Solution
-
4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO?), a representative member of the inexpensive and environmentally-friendly N-triazinylammonium family of sulfonates, has been found to be a very effective coupling reagent for the synthesis of amides, esters and peptides in solution. This study confirms the usefulness of DMT/NMM/TsO? for peptide synthesis in solution, starting from Z-, Fmoc-, and Boc-protected substrates as well as unnatural building blocks. Peptide synthesis with DMT/NMM/TsO? produced high yields, with high crude product purity and low risk of racemization. In all cases, stoichiometric amounts of reagents were used and the standard synthetic procedure, without the need for time-consuming optimization stages or expensive chromatographic purification. DMT/NMM/TsO? was also found to be very useful for the synthesis of oligopeptides using a fragment coupling strategy.
- Fraczyk, Justyna,Kaminski, Zbigniew J.,Katarzynska, Joanna,Kolesinska, Beata
-
-
- Tandem deprotection/coupling for peptide synthesis in water at room temperature
-
A tandem deprotection/coupling sequence is reported for solution-phase peptide synthesis in water under micellar catalysis conditions using the designer surfactant TPGS-750-M. Cbz deprotection followed by peptide coupling in the presence of COMU and 2,6-lutidine afforded polypeptides containing up to 10 amino acid residues. A broad scope characterizes this new technology. No epimerization has been detected. The associated E Factors, as a measure of "greenness" and known to be extremely high for peptide couplings, have been reduced to less than 10 due to the step-economy and minimal amounts of organic solvent needed for product extraction.
- Cortes-Clerget, Margery,Berthon, Jean-Yves,Krolikiewicz-Renimel, Isabelle,Chaisemartin, Laurent,Lipshutz, Bruce H.
-
supporting information
p. 4263 - 4267
(2017/09/28)
-
- 9-Silafluorenyl Dichlorides as Chemically Ligating Coupling Agents and Their Application in Peptide Synthesis
-
A fundamentally simple, mild, and practical procedure for peptide bond formation is reported that employs a stoichiometric amount of easy-to-access 9-silafluorenyl dichlorides as the coupling agent. Without initial preactivation or elaboration of the carboxylic acid or amine termini of the amino acids, the developed reagent is proposed to act through an unprecedented chemical ligation mechanism, bringing the two coupling partners together before being subsequently eliminated. The desired amides or peptide bonds are thus furnished in good yields and with low to no epimerization.
- Aspin, Samuel J.,Taillemaud, Sylvain,Cyr, Patrick,Charette, André B.
-
supporting information
p. 13833 - 13837
(2016/10/26)
-
- A green route for the synthesis of a bitter-taste dipeptide combining biocatalysis, heterogeneous metal catalysis and magnetic nanoparticles
-
There is increasing demand for green technologies to produce high-solubility and low-toxicity compounds with potential application in the food industry. This study aimed to establish a clean, synthetic route for preparing the bitter-taste dipeptide Ala-Phe, a potential substitute for caffeine as a food additive. Synthesis of Z-Ala-Phe-OMe starting from Z-Ala-OH and HCl·Phe-OMe was catalysed by thermolysin at 50 °C in buffer (step 1). Z-Ala-Phe-OMe ester hydrolysis to give Z-Ala-Phe-OH at 37 °C in 30% acetonitrile/buffer was catalysed by α-bovine chymotrypsin (αCT), protease with esterase activity (step 2). Hydrogenation of Z-Ala-Phe to give the desired Ala-Phe was catalysed by C/Pd in methanol (step 3). Steps 2 and 3 were optimized by using the magnetically recoverable recycling enzyme Fe3O4@silica-αCT and the magnetically recoverable metal nanocatalyst Fe3O4@silica-Pd, respectively. This inspiring combination of technologies and the original results demonstrate the suitability of using enzymes, metal catalyst and magnetic nanoparticles for easy, economical, stereoselective, clean production of an important target compound. Besides, they add to the development of peptide chemistry and catalysis.
- Ungaro, Vitor A.,Liria, Cleber W.,Romagna, Carolina D.,Costa, Natália J. S.,Philippot, Karine,Rossi, Liane M.,Machini, M. Teresa
-
p. 36449 - 36455
(2015/05/13)
-
- A one-pot saponification-coupling sequence suitable for C-terminus peptide elongation using lithium carboxylates
-
An efficient procedure has been developed for the saponification of common peptide esters, followed by straightforward coupling of the lithium carboxylate. Adding some water to the reaction medium gave faster saponification and did not interfere with the coupling reagent. As peptide chemistry constitutes a major application of the amidation reaction, amino acid substrates were chosen for this study, monitoring both yields and epimerization of the peptides obtained. Georg Thieme Verlag Stuttgart New York.
- Azzouz, Rabah,Petit, Sylvain,Rouchet, Jean-Baptiste,Bischoff, Laurent
-
supporting information
p. 1843 - 1846
(2014/08/18)
-
- The method of preparation of enantiomerically enriched products of condensation from racemic acids or acids of the low enentiomeric purity
-
The method of obtaining enantiomerically enriched condensation products consists of subjecting a racemic acid or an acid of low enantiomeric purity to the action of a condensing reagent - a chiral N-triazinylammonium tetrafluoroborate (formula 1), a chira
- -
-
Page/Page column 7
(2012/03/08)
-
- N-Triazinylammonium salts, a method of preparation and uses thereof
-
The invention provides inner quaternary N-triazinyl- ammonium salts of sulphonic acids, of the Formula 1, a method of preparation thereof and a use thereof as condensation reagents in condensation reactions.
- -
-
Page/Page column 9-10
(2012/02/04)
-
- Performance improvement of araujiain, a cystein phytoprotease, by immobilization within calcium alginate beads
-
The effect of immobilization within alginate beads on the performance of araujiain in aqueous and non-aqueous media was studied. Optimum pH and temperature, thermal and pH-stability, kinetic parameters and operational stability were determined. Entrapped
- Quiroga, Evelina,Illanes, Cristián Omar,Ochoa, Nelio Ariel,Barberis, Sonia
-
p. 1029 - 1034
(2013/01/10)
-
- The design, synthesis, and application of a chiral coupling reagent derived from strychnine for the enantioselective activation of a carboxylic group
-
The concept of a chiral coupling reagent for the enantioselective synthesis of peptides with a predictable configuration and enantiomeric purity from racemic substrates is presented. The reagent was prepared by treatment of strychninium tetrafluoroborate with 2-chloro-4,6-dimethoxy-1,3,5-triazine in the presence of sodium bicarbonate yielding N-(4,6-dimethoxy-1,3,5-triazin-2-yl)strychninium tetrafluoroborate in high yield, which is stable at room temperature, and in a broad range of solvents gave enriched Z-Ala-Phe-OMe (dr from 95/5 to 60/40) in high yield with d-configuration on the alanine residue starting from rac-Z-Ala-OH.
- Kolesińska, Beata,Kasperowicz, Katarzyna,Sochacki, Marek,Mazur, Adam,Jankowski, Stefan,Kamiński, Zbigniew J.
-
supporting information; experimental part
p. 20 - 22
(2010/03/03)
-
- Fully enzymatic peptide synthesis using C-terminal tert-butyl ester interconversion
-
Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides with some important advantages. For instance, stoichiometric amounts of expensive coupling reagents are not required an
- Nuijens, Timo,Cusan, Claudia,Van Dooren, Theodorus J. G. M.,Moody, Harold M.,Merkx, Remco,Kruijtzer, John A. W.,Rijkers, Dirk T. S.,Liskamp, Rob M. J.,Quaedflieg, Peter J. L. M.
-
experimental part
p. 2399 - 2404
(2011/02/21)
-
- Aza-peptidyl michael acceptor and epoxide inhibitors - Potent and selective inhibitors of Schistosoma mansoni and Ixodes ricinus legumains (asparaginyl endopeptidases)
-
Aza-peptide Michael acceptors and epoxides with the general structure of YCO-Ala-Ala-AAsn-trans-CH=CHCOR and YCO-Ala-Ala-AAsn-EP-COR, respectively, are shown to be potent inhibitors of asparaginyl endopeptidases (legumains) from the bloodfluke, Schistosoma mansoni (SmAE), and the hard tick, Ixodes ricinus (IrAE). Structure-activity relationships (SARs) were determined for a set of 41 aza-peptide Michael acceptors and eight aza-peptide epoxides. Both enzymes prefer disubstituted amides to monosubstituted amides in the P10 position, and potency increased as we increased the hydrophobicity of the inhibitor in this position. Extending the inhibitor to P5 resulted in increased potency, especially against IrAE, and both enzymes prefer small over large hydrophobic residues at P2. Aza-peptide Michael acceptor inhibitors are more potent than aza-peptide epoxide inhibitors, and for some of these compounds, second-order inhibiton rate constants are the fastest yet discovered. Given the central functions of these enzymes in both parasites, the data presented here may facilitate the eventual design of selective antiparasitic drugs.
- Ovat, Asli,Muindi, Fanuel,Fagan, Crystal,Brouner, Michelle,Hansell, Elizabeth,Dvo?ák, Jan,Sojka, Daniel,Kopá?ek, Petr,McKerrow, James H.,Caffrey, Conor R.,Powers, James C.
-
experimental part
p. 7192 - 7210
(2010/07/05)
-
- Activation of carboxylic acids as their active esters by means of tert-butyl 3-(3,4-dihydrobenzotriazine-4-on)yl carbonate
-
Carboxylic acids were activated in the presence of DMAP with tert-butyl carbonates (BOC-OX) 1, which were prepared in situ by reaction of X-OH and di-tert-butyl dicarbonate (BOC2O). The most efficient active carbonate proved to be tert-butyl 3-(3,4-dihydrobenzotriazine-4-on)yl carbonate 1a, leading to efficient formation of benzotriazinonyl esters 3 and 6, which are intermediates in reactions with primary and secondary amines to afford amides or peptides in good yield. By-products in the formation of 3 or 6 are the environmentally safe tert-BuOH and CO2. The hindered amino acid AIB also forms a dipeptide in good yield.
- Basel, Yochai,Hassner, Alfred
-
p. 2529 - 2533
(2007/10/03)
-
- Scavenging of fluorinated N,N′-dialkylureas by hydrogen binding: A novel separation method for fluorous synthesis
-
(matrix presented) A dramatic solubility increase in fluorous solvents is observed for N,N′-di(polyfluoroalkyl)ureas when hydrogen binding complexes are formed with commercially available perfluoroalkanoic acid scavengers. As a case example, analytically pure peptides and esters are obtained using this novel separation method.
- Palomo, Claudio,Aizpurua, Jesus M.,Loinaz, Iraida,Fernandez-Berridi, Maria Jose,Irusta, Lourdes
-
p. 2361 - 2364
(2007/10/03)
-
- Tandem deprotection-coupling of N(α)-Alloc-amino acids by use of ternary systems Pd cat./PhSiH3/carboxy-activated amino acid
-
N(α)-allyloxycarbonyl derivatives of amino acids undergo smooth coupling with various carboxy-activated partners when treated with phenylsilane (PhSiH3) in the presence of catalytic amounts of tetrakis- (triphenylphosphine) palladium.
- Thieriet, Nathalie,Gomez-Martinez, Paloma,Guibe, Francois
-
p. 2505 - 2508
(2007/10/03)
-
- 3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT): a new coupling reagent with remarkable resistance to racemization.
-
[formula: see text] The new crystalline phosphate reagent 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) mediates amide bond formation with a remarkable resistance to racemization. Comparative racemization studies were carried out and DEPBT proved to be superior to typical phosphonium and uronium coupling reagents. DEPBT is easily prepared and is exceedingly stable with a shelf life of months at room temperature. The advantageous properties of DEPBT render it a useful and unique addition to the arsenal of coupling reagents.
- Li,Jiang,Ye,Fan,Romoff,Goodman
-
-
- A novel organophosphorus compound as a coupling reagent for peptide synthesis
-
3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4 (3H)-one 1 is a new organophosphorus compound which can be used as an efficient coupling reagent for peptide synthesis by either solution or solid phase coupling.
- Fan, Chong-Xu,Hao, Xiao-Lin,Ye, Yun-Hua
-
p. 1455 - 1460
(2007/10/03)
-
- Rapid, one-pot synthesis of urethane-protected tripeptides
-
Urethane-protected tripeptides are synthesized in solution, without isolation of purification of intermediates, using urethane-protected N-carboxyanhydrides as coupling reagents and hydrogenation for removal of N-protection.
- Zhu, Yun-Fei,Fuller, William D.
-
p. 807 - 810
(2007/10/02)
-
- A low-epimerizing peptide coupling reagent based on the rearrangement of a carboxylic-sulfonic mixed anhydride
-
A series of peptides has been prepared using an o-hydroxybenzenesulfonyl chloride as the condensation reagent. Experimentally, the coupling is a one pot two-steps reaction: formation and aminolysis of a substituted aryl ester. The first step occurs by an
- Cabaret, Daniel,Wakselman, Michel
-
p. 9561 - 9564
(2007/10/02)
-
- Acylation reactions mediated by tantalum carboxylates
-
Facile nucleophilic attack on coordinated carboxylate ligaods is reported: complexes of tantalum(V) react rapidly with amines and amino acid esters to give the corresponding amides. Cyclopentadienyltantalum(V) amino acid carboxylate complexes have been pr
- Joshi, Kiran,Bao, Jiang,Goldman, Alan S.,Kohn, Joachim
-
p. 6649 - 6652
(2007/10/02)
-
- N-Hydroxyamide-containing Heterocycles. New Effective Additives for Peptide Synthesis by the Dicyclohexylcarbodiimide Method
-
N-Hydroxyamide-containing heterocycles, 1-hydroxy-4,6-dimethyl-2(1H)-pyrimidinone and -5,6-dimethyl-2(1H)-pyrazinone, are prepared.Judging from the result of model dipeptide (Z-Ala-Phe-OMe) formation, these compounds are found to be new effective additive
- Katoh, Akira,Ohkanda, Junko,Itoh, Yoshifumi,Mitsuhashi, Keiryo
-
p. 2009 - 2012
(2007/10/02)
-
- An improved method for the synthesis of active esters of N-protected amino acids and subsequent synthesis of dipeptides
-
4-Dimethylaminopyridine-catalyzed reaction of mixed carbonates 3 with N-protected amino acids 4 gave the corresponding active esters 5-9, from which dipeptides 11-18 were synthesized by aminolysis with amino acids 10.
- Takeda,Ayabe,Suzuki,Konda,Harigaya
-
p. 689 - 691
(2007/10/02)
-
- A NEW CONVENIENT APPROACH TO PEPTIDE SYNTHESIS
-
A new and highly efficient method based on a redox reaction using diphenyl diselenide and tributylphosphine for the general synthesis of peptides is described.The side reaction due to selenophenol formation is overcome by using chalcone as a scavenger or
- Singh, Usha,Ghosh, Sunil K.,Chadha, Mohindra S.,Mamdapur, Vasant R.
-
p. 255 - 258
(2007/10/02)
-
- KINETICS OF THE ALKALINE HYDROLYSIS OF SEVERAL N-BENZYLOXYCARBONYLDIPEPTIDE METHYL AND ETHYL ESTERS
-
The reaction rates of the alkaline hydrolysis of synthesized N-protected dipeptide methyl and ethyl esters were studied systematically.From the kinetic data the energies of activation, the pre-exponential factors and the reference values at 40 deg C were calculated.The rate of hydrolysis shows to be strongly dependent on the C-terminal amino acid in the sequence Gly >> Ala/Met/Phe > Leu >> Val/Pro.Surprisingly the N-terminal amino acid also exerts an effect, but in a different sequence.N-Terminal Phe in particular shows a relative accelerating effect.Remarkable is the significantly faster ester hydrolysis of glycine containing dipeptide ethyl esters in ethanol/water compared to the corresponding methyl esters in methanol/water.
- Hoogwater, D. A.,Peereboom, M.
-
p. 5325 - 5332
(2007/10/02)
-
- Amino acids and peptides. XXIII. Synthesis of N alpha-protected amino acid 6-chloro-2-pyridyl esters and their evaluation for peptide synthesis.
-
6-Chloro-2-pyridyl esters (OPyCl) of N alpha-benzyloxycarbonyl and tert-butyloxycarbonylamino acids were synthesized by the N,N'-dicyclohexylcarbodiimide (DCC) method from the acids and 6-chloro-2-hydroxypyridine in dimethylformamide (DMF). The reactivity of the 6-chloro-2-pyridylester with amino group is much higher than that of the corresponding 2-pyridyl ester (OPy) and p-nitrophenyl esters (ONp) in dioxane and DMF, and a peptide bond is formed without acylation at the side chain hydroxyl group of amino acids. Z-Asp(OBzl)-OPyCl reacted with amino acid methyl esters in dioxane to give the corresponding dipeptide without any detectable aspartimide formation.
- Tsuboi,Okada
-
-
- Facile Conversions of Carboxylic Acids into Amides, Esters, and Thioesters Using 1,1'-Oxalyldiimidazole and 1,1'-Oxalyldi(1,2,4-triazole)
-
Aliphatic, aromatic, and heteroaromatic carboxylic acids react with 1,1'-oxalyldiimidazole (1) or 1,1'-oxalyldi(1,2,4-triazole) (2) in acetonitrile for 40 min at 40 degC to give the corresponding 1-acylazole intermediates (11), which promptly undergo aminolysis and alcoholysis to form amides (13) including dipeptides (14), esters (16), and thioesters (19).These findings show that both 1 and 2 can be utilized as condensing reagents for the synthesis of carboxylic acid derivatives.Keywords --- 1,1'-oxalyldiimidazole; 1,1'-oxalyldi(1,2,4-triazole); 1,1'-carbonyldiimidazole; 1-acylazole; condensing reagent; amidation; esterification; dipeptide; aminolysis; alcoholysis
- Kitagawa, Tokujiro,Kuroda, Hiroko,Sasaki, Hideaki,Kawasaki, Koichi
-
p. 4294 - 4301
(2007/10/02)
-
- AMINO ACIDS AND PEPTIDES. VIII. A WATER - SOLUBLE ACTIVE ESTER, PHENOLSULFONIC ACID DERIVATIVE
-
N-protected amino acid 4-phenolsulfonic acid derivative esters, such as 2,6-dibromo-4-sulfophenyl ester sodium salt, 2,6-dichloro-4-sulfophenyl ester potassium salt and 2-nitro-4-sulfophenyl ester sodium salt, were prepared.These esters are water - soluble active esters, and were applied for rhe synthesys of Leu-enkephalin.Keywords - water - soluble active ester; 2,6-dichloro-4-sulfophenyl ester; 2,6-dibromo-4-sulfophenyl ester; 2-nitro-4-sulfophenyl ester; peptide synthesis; Leu-enkephalin
- Kawasaki, Koichi,Tsuji, Toshiki,Maeda, Misuko,Matsumoto, Tatsuya,Hirase, Katsuhiko
-
p. 1044 - 1048
(2007/10/02)
-
- 2,2'-CARBONYL-BIS(3,5-DIOXO-4-METHYL-1,2,4-OXADIAZOLIDINE) : I- A NEW REAGENT FOR THE PREPARATION OF CARBAMATES AND AMIDES, APPLICATION TO THE SYNTHESIS OF DIPEPTIDES.
-
2,2'-Carbonyl bis (3,5-dioxo-4-methyl-1,2,4-oxadiazolidine) was prepared and used for the synthesis of various carbamates and dipeptides.
- Denarie, Michel,Grenouillat, Denis,Malfroot, Thierry,Senet, Jean-Pierre,Sennyey, Gerard,Wolf, Patrick
-
p. 5823 - 5826
(2007/10/02)
-
- A SIMPLE METHOD FOR SYNTHESIS OF AMIDES AND PEPTIDES THROUGH ACYL CHLORIDES. A RAPID SYNTHESIS OF THYROTROPIN RELEASING HORMONE
-
By improvement of the classical SOCl2-pyridine method for the preparation of acid chlorides, amides and optically pure peptides were synthesized rapidly in a simple manner from DCHA (dicyclohexylammonium) salts of carboxylic acids.This modified SOCl2-pyridine method was applied to a rapid synthesis of TRH.
- Matsuda, Fuyuhiko,Itoh, Shin,Hattori, Noritaka,Yanagiya, Mitsutoshi,Matsumoto, Takeshi
-
p. 3625 - 3631
(2007/10/02)
-
- 3-AMINOACYL-TETRAHYDROTHIAZOLE-2-THIONE AS AN ACTIVE AMIDE FOR PEPTIDE SYNTHESIS (I)
-
3-Aminoacyl-tetrahydrothiazole-2-thione can be used as an active amide for peptide synthesis.A series of peptides have been synthesized with satisfactory yields by this methods.
- Chung-hsi, Li,Yuen-hwa, Yieh,Yao, Lin,Yong-jun, Lu,Ai-hsueh, Chi,Chi-yi, Hsing
-
p. 3467 - 3470
(2007/10/02)
-
- Peptide Synthesis by Means of Immobilized Enzymes. I. Immobilized α-Chimotripsin
-
α-Chymotrypsin covalently bound to silica, enzacryl AA, and enzacryl AH catalyzes peptide bond formation between N-protected dipeptide methyl esters and H-Leu-NH2 with results similar to those with the free enzyme.The influence of water-miscible and water
- Koennecke, Andreas,Bullerjahn, Ralf,Jakubke, Hans-Dieter
-
p. 469 - 482
(2007/10/02)
-