2592-95-2Relevant academic research and scientific papers
Synthesis and morpholinolysis of N,N-diethyl carbamate derivatives of 4- HOAt, 7-HOAt and HOBt
Khattab, Sherine N.,Hassan, Seham Y.,Hamed, Ezzat A.,El-Faham, Ayman
, p. 247 - 251 (2007)
N,N-Diethyl carbamates of 1-hydroxy-7-azabenzotriazole (7-HOAt), 1-hydroxy-4-azabenzotriazole (4-HOAt), 1-hydroxybenzotriazole (HOBt), and 1-hydroxypyrrolidine-2,5-dione have been synthesised. The reactivities of these active esters have been determined by studying the kinetics and mechanism of their morpholinolysis in acetonitrile at different temperatures.
Unwanted hydrolysis or α/β-peptide bond formation: How long should the rate-limiting coupling step take?
Goldschmidt G?z, Viktória,Nagy, Adrienn,Farkas, Viktor,Keszei, Ern?,Perczel, András
, p. 30720 - 30728 (2019/10/28)
Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
Highly efficient one-pot assembly of peptides by double chemoselective coupling
Sampaio-Dias, Ivo E.,Sousa, Carlos A. D.,Silva-Reis, Sara C.,Ribeiro, Sara,García-Mera, Xerardo,Rodríguez-Borges, José E.
supporting information, p. 7533 - 7542 (2017/09/27)
This study describes a methodological advancement in solution-phase peptide synthesis via the development of a convenient and operational protocol to synthesize oligopeptides in a one-pot three-step cascade method, in which two peptide bonds are introduced chemoselectively. Tri- to hexapeptides were obtained in high global yields (80-95%) with virtually no epimerization as determined via HPLC. The methodology described herein represents a faster, easier and milder approach to the synthesis of peptides, and it operates at equimolar amounts. This protocol comprises the formation of secondary and tertiary amides and is compatible with Z, Boc and Fmoc N-protecting groups as well as the use of d/l and non-proteinogenic amino acids.
N-aryl benzotriazole type nitrogen oxygen derivative and synthesis method thereof
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Paragraph 0040-0042, (2016/11/24)
The invention discloses an N-aryl benzotriazole type nitrogen oxygen derivative and a synthesis method thereof. The N-aryl benzotriazole type nitrogen oxygen derivative has the structure shown by the formula (I), the preparation method comprises the steps that an N-hydroxybenzotriazole derivative of the structure shown by the formula (II), an organo-boron reagent of the structure shown by the formula (III), cupric salt and an alkaline matter are taken and placed into an organic solvent, reaction is performed under the condition of oxygen, and a target crude product is prepared. The method is easy to control, and the period is short; the prepared crude product has excellent antineoplastic activity. The compounds of the structures shown by the formula (I), the formula (II) and the formula (III) are as below respectively. (Please see the chemical formulas in the description.).
ULTRAVIOLET RADIATION ABSORBING POLYETHERS
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Page/Page column, (2014/02/15)
A polymer composition comprising a linear ultraviolet radiation absorbing polyether that comprises a chemically bound UV-chromophore.
Importance of π-stacking interactions in the hydrogen atom transfer reactions from activated phenols to short-lived N-oxyl radicals
Mazzonna, Marco,Bietti, Massimo,Dilabio, Gino A.,Lanzalunga, Osvaldo,Salamone, Michela
, p. 5209 - 5218 (2014/06/23)
A kinetic study of the hydrogen atom transfer from activated phenols (2,6-dimethyl- and 2,6-di-tert-butyl-4-substituted phenols, 2,2,5,7,8- pentamethylchroman-6-ol, caffeic acid, and (+)-cathechin) to a series of N-oxyl radical (4-substituted phthalimide-N-oxyl radicals (4-X-PINO), 6-substituted benzotriazole-N-oxyl radicals (6-Y-BTNO), 3-quinazolin-4-one-N-oxyl radical (QONO), and 3-benzotriazin-4-one-N-oxyl radical (BONO)), was carried out by laser flash photolysis in CH3CN. A significant effect of the N-oxyl radical structure on the hydrogen transfer rate constants (kH) was observed with kH values that monotonically increase with increasing NO-H bond dissociation energy (BDENO-H) of the N-hydroxylamines. The analysis of the kinetic data coupled to the results of theoretical calculations indicates that these reactions proceed by a hydrogen atom transfer (HAT) mechanism where the N-oxyl radical and the phenolic aromatic rings adopt a π-stacked arrangement. Theoretical calculations also showed pronounced structural effects of the N-oxyl radicals on the charge transfer occurring in the π-stacked conformation. Comparison of the kH values measured in this study with those previously reported for hydrogen atom transfer to the cumylperoxyl radical indicates that 6-CH3-BTNO is the best N-oxyl radical to be used as a model for evaluating the radical scavenging ability of phenolic antioxidants.
One-step radiosynthesis of 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP); Improved preparation of radiolabeled peptides for PET imaging
Haskali, Mohammad B.,Roselt, Peter D.,Karas, John A.,Noonan, Wayne,Wichmann, Christian W.,Katsifis, Andrew,Hicks, Rodney J.,Hutton, Craig A.
, p. 726 - 730 (2014/01/06)
The versatile 18F-labeled prosthetic group, 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP), was synthesized in a single step in 45 min from 4-nitrophenyl 2-bromopropionate, with a decay corrected radiochemical yield of 26.2% ± 2.2%. Employing this improved synthesis of [18F]NFP, [18F]GalactoRGD - the current 'gold standard' tracer for imaging the expression of αVβ 3 integrin - was prepared with high specific activity in 90 min and 20% decay corrected radiochemical yield from [18F]fluoride. 4-Nitrophenyl 2-[18F]fluoropropionate ([18F]NFP), was synthesized in a single radiochemical step in 45 minutes and 26% d.c. radiochemical yield from 4-nitrophenyl 2-bromopropionate. Employing this improved synthesis of [18F]NFP, [18F]GalactoRGD was prepared with high specific activity in 90 minutes and 20% d.c. radiochemical yield from [18F]fluoride. Copyright
METHOD FOR THE MANUFACTURE OF DEGARELIX
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, (2012/03/08)
In a step-wise synthesis of degarelix comprising 0.3% by weight or less of 4-([2(5-hydantoyl)]acetylamino)-phenylalanine analog on (solid support)-NH2 a step comprises providing a solution of an amino acid or peptide of which the α-amino group is protected by Fmoc; contacting the support with the solution in the presence of reagent for forming a peptide bond between a carboxyl group of the amino acid or peptide and (solid support)-NH2; removing Fmoc by contacting the support with an organic base, in particular piperidine, in an organic solvent. Also disclosed is degarelix of high purity prepared by the method of the invention and the use of Fmoc in the synthesis of degarelix.
Spectrophotometric determination of pKa's of 1-Hydroxybenzotriazole and oxime derivatives in 95% acetonitrile-water
Fathalla, Magda Fouad,Khattab, Sherine Nabil
experimental part, p. 324 - 332 (2012/05/04)
1-hydroxybenzotriazole derivatives are used with carbodiimide as additives to generate active esters during peptide bond formation. They are also used as additives during the peptide bond formation. Dissociation constants of the 1-hdroxybenzotriazole (HOBt) and its derivatives, 1- hydroxy-6- chlorobenzotriazole, 1-hydroxy-6-trifluoromethylbenzotriazole, 1-hydroxy-6-nitrobenzotriazole were determined spectrophotometrically in 95% acetonitrile-water. In addition, 7-aza-1- hydroxybenzotriazole (7-HOAt) and 4-aza-1-hydroxybenzotriazole (4-HOAt) were also studied. Recently, oxyma was reported as a good replacement for the benzotriazole derivatives. As alcoholic components of active esters, the oximes seem to be good leaving groups. Therefore it was expected, that the strongly acidic and nucleophilic oximes, which possess electron-withdrawing groups in the molecule, are suitable as additives during the peptide bond formation. The dissociation constant of some oximes,such as diethyl 2-(hydroxyimino)malonate, ethyl 2-cyano-2-(hydroxyimino) acetate (oxyma), hydroxycarbonimidoyl dicyanide and N-hydroxypicolinimidoyl cyanide in 95% acetonitrile-water are reported.
Discovery of 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate as a potential antiproliferative agent by inhibiting histone deacetylase
Fu, Jie,Yang, Ying,Zhang, Xue-Wei,Mao, Wen-Jun,Zhang, Zhi-Ming,Zhu, Hai-Liang
experimental part, p. 8457 - 8462 (2011/02/26)
Twenty-one benzotriazoles (3-16 and 18-24) were synthesized and half of them (5, 8-16, 20, and 21) were reported for the first time. Their antiproliferative activities against three human cancer cells were assayed. It revealed that 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate (9) showed considerable activity against three human cancer cell lines with the half maximal inhibitory concentration (IC50) values of 1.2-2.4 nM, which were close to the value of the positive control, doxorubicin. Further investigation indicated compound 9 was a potential histone deacetylase inhibitor (IC50 = 9.4 μM) and its binding mode was simulated using docking method.
