- Structure based design, synthesis, and biological evaluation of imidazole derivatives targeting dihydropteroate synthase enzyme
-
In this study, we have designed and synthesized 2-((5-acetyl-1-(phenyl)-4-methyl-1H-imidazol-2-yl)thio)-N-(4-((benzyl)oxy)phenyl) acetamide derivatives. Antimicrobial activities of all the imidazole derivatives have been examined against Gram-positive and Gram-negative bacteria and results showed that the conjugates have appreciable antibacterial activity. Besides, several analogous were evaluated for their in vitro antiresistant bacterial strains such as Extended-spectrum beta-lactamases (ESBL), Vancomycin-resistant Enterococcus (VRE), and Methicillin-resistant Staphylococcus aureus (MRSA). The SAR revealed that the 12l compound resulted in potency against all bacterial strains as well as ESBL, VRE, and MRSA strains. Lipinski's rule of five, and ADME studies were preformed for all the synthesized compounds with Staphylococcus aureus dihydropteroate synthase (saDHPS) protein (PDB ID: 6CLV) and were found standard drug-likeness properties of conjugates. Moreover, the binding mode of the ligands with the protein study has been examined by molecular docking and results are quite promising. Besides, all the analogous were tested for their in vitro antituberculosis, antimalarial, and antioxidant activity.
- Daraji, Drashti G.,Rajani, Dhanji P.,Rajani, Smita D.,Pithawala, Edwin A.,Jayanthi, Sivaraman,Patel, Hitesh D.
-
supporting information
(2021/02/16)
-
- Kinetic study on nucleophilic substitution reactions of 4-Nitrophenyl X-Substituted-Benzoates with potassium ethoxide: Reaction mechanism and role of K+ Ion
-
A kinetic study on nucleophilic substitution reactions of 4-nitrophenyl X-substituted-benzoates (7a-i) with EtOK in anhydrous ethanol at 25.0 ± 0.1 °C is reported. The plots of pseudo-first-order rate constants (kobsd) vs. [EtOK] curve upward. Dissection of kobsd into the second-order rate constants for the reactions with the dissociated EtOV and ion-paired EtOK (i.e., kEtO-and kEtOK, respectively) has revealed that the ion-paired EtOK is more reactive than the dissociated EtOV. Hammett plots for the reactions of 7a-i with the dissociated EtOV and ion-paired EtOK exhibit excellent linear correlations with aX = 3.00 and 2.47, respectively. The reactions have been suggested to proceed through a stepwise mechanism in which departure of the leaving-group occurs after the RDS. The correlation of the kEtOK/kEtO{ ratio with the aX constants exhibits excellent linearity with a slope of V0.53. It is concluded that the ion-paired EtOK catalyzes the reaction by increasing the electrophilicity of the reaction center rather than by enhancing the nucleofugality of the leaving group.
- Kim, Song-I,Kim, Min-Young,Um, Ik-Hwan
-
p. 225 - 230
(2014/02/14)
-
- Ruthenium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols
-
An efficient methodology to access benzoate derivatives via tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols catalyzed by ruthenium/NHC was developed. This operationally simple one-pot process uses O2 as the clean oxidant, producing esters in good to excellent yields.
- Zhang, Di,Pan, Changduo
-
experimental part
p. 41 - 45
(2012/06/18)
-
- Palladium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols
-
A palladium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols to access aryl benzoate derivatives is described. The procedure tolerates a series of functional groups, such as methoxy, nitro, cyano, chloro, fluoro and bromo groups. Thus, it represents a practically alternative method to access aryl benzoate derivatives.
- Luo, Fang,Pan, Changduo,Cheng, Jiang,Chen, Fan
-
supporting information; experimental part
p. 5878 - 5882
(2011/09/12)
-
- Palladium/NHC-catalyzed oxidative esterification of aldehydes with phenols
-
A palladium-catalyzed oxidative esterification of aldehydes with phenols is described, using air as the clean oxidant. This reaction tolerates many functional groups, providing esters with yields ranging from moderate to excellent.
- Zhang, Manli,Zhang, Shouhui,Zhang, Guoying,Chen, Fan,Cheng, Jiang
-
experimental part
p. 2480 - 2483
(2011/05/16)
-
- Aminolysis of Y-substituted-phenyl 2-methoxybenzoates in acetonitrile: Effect of the o-methoxy group on reactivity and reaction mechanism
-
Second-order rate constants (kN) were measured for aminolyses of Y-substituted-phenyl 2-methoxybenzoates 2a-i and 4-nitrophenyl X-substituted-benzoates 3a-j in MeCN at 25.0 °C. The Bronsted-type plot for the reactions of 2a-i with piperidine curves downward, indicating that a change in rate-determining step (RDS) occurs. The Hammett plot for the reactions of 3a-j with piperidine consists of two intersecting straight lines, which might be taken as evidence for a change in RDS. However, the nonlinear Hammett plot has been suggested not to be due to a change in RDS but rather to the stabilization of the ground state of substrates possessing an electron-donating group (EDG) (e.g., 3a-c) through a resonance interaction, since the corresponding Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ = 0.54 and r = 1.54. The ρ value found for the reactions of 3a-j in MeCN is much smaller than that reported previously for the corresponding reactions in H2O (i.e., ρ = 0.75). It is proposed that the reactions of 3a-j in MeCN proceed through a forced concerted mechanism due to instability of T± in the aprotic solvent, while the reactions of 2a-i proceed through a stepwise pathway with a stabilized T ± through an intramolecular H-bonding interaction.
- Um, Ik-Hwan,Bae, Ae Ri
-
experimental part
p. 7510 - 7515
(2011/11/13)
-
- Investigation of a general base mechanism for ester hydrolysis in C-C hydrolase enzymes of the α/β-hydrolase superfamily: A novel mechanism for the serine catalytic triad
-
Previous mechanistic and crystallographic studies on two C-C hydrolase enzymes, Escherichia coli MhpC and Burkholderia xenovorans BphD, support a general base mechanism for C-C hydrolytic cleavage, rather than the nucleophilic mechanism expected for a ser
- Li, Jian-Jun,Bugg, Timothy D. H.
-
p. 507 - 513
(2008/03/28)
-
- Structure-reactivity correlations in nucleophilic substitution reactions of Y-substituted phenyl X-substituted benzoates with anionic and neutral nucleophiles
-
A kinetic study is reported for the reactions of 4-nitrophenyl X-substituted benzoates (1a-l) and Y-substituted phenyl benzoates (2a-l) with two anionic nucleophiles (OH- and CN-) and three amines (piperidine, hydrazine, and glycylglycine) in 80 mol% H2O-20 mol% dimethyl sulfoxide (DMSO) at 25.0 ± 0.1 °C. Each Hammett plot exhibits two intersecting straight lines for the reactions of 1a-l with the anionic nucleophiles and piperidine, while the Yukawa-Tsuno plots for the same reactions are linear. The Hammett plots for the reactions of 2a-l with hydrazine and glycylglycine demonstrate much better linear correlations with σ- constants than with σ° or σ constants, indicating that the leaving group departure occurs at the rate determining step (RDS). On the contrary, σ- constants result in poorer Hammett correlation than σ° constants for the corresponding reactions with OH- and CN-, indicating that the leaving group departure occurs after the RDS for the reactions with the anionic nucleophiles. The large ρX value (1.7 ± 0.1) obtained for the reactions of 1a-l with the anionic nucleophiles supports the proposal that the reactions proceed through an addition intermediate with its formation being the RDS. The Royal Society of Chemistry 2006.
- Um, Ik-Hwan,Lee, Ji-Youn,Fujio, Mizue,Tsuno, Yuho
-
p. 2979 - 2985
(2008/02/11)
-
- Evidence of substituent-induced electronic interplay. Effect of the remote aromatic ring substituent of phenyl benzoates on the sensitivity of the carbonyl unit to electronic effects of phenyl or benzoyl ring substituents
-
Carbonyl carbon 13C NMR chemical shifts δC(C=O) measured in this work for a wide set of substituted phenyl benzoates p-Y-C 6H4CO2C6H4-p-X (X = NO2, CN, Cl, Br, H, Me, or MeO; Y = NO2, Cl, H, Me, MeO, or NMe2) have been used as a tool to study substituent effects on the carbonyl unit. The goal of the work was to study the cross-interaction between X and Y in that respect. Both the phenyl substituents X and the benzoyl substituents Y have a reverse effect on δC(C=O). Electron-withdrawing substituents cause shielding while electron-donating ones have an opposite influence, with both inductive and resonance effects being significant. The presence of cross-interaction between X and Y could be clearly verified. Electronic effects of the remote aromatic ring substituents systematically modify the sensitivity of the C=O group to the electronic effects of the phenyl or benzoyl ring substituents. Electron-withdrawing substituents in one ring decrease the sensitivity of δC(C=O) to the substitution of another ring, while electron-donating substituents inversely affect the sensitivity. It is suggested that the results can be explained by substituent-sensitive balance of the contributions of different resonance structures (electron delocalization, Scheme 1).
- Neuvonen, Helmi,Neuvonen, Kari,Pasanen, Paavo
-
p. 3794 - 3800
(2007/10/03)
-
- Pd-catalyzed decarbonylative olefination of aryl esters: Towards a waste-free Heck reaction
-
Easy and clean: A palladium (0)-catalyzed decarbonylative Heck olefination of activated esters of aryl, heteroaryl, and vinyl carboxylic acids opens up an opportunity for a novel waste-free Heck olefination process (see scheme).
- Goossen, Lukas J.,Paetzold
-
p. 1237 - 1241
(2007/10/03)
-
- Nucleophilic displacement at the benzoyl centre: A study of the change in geometry at the carbonyl carbon atom
-
The second-order rate constants for the reaction between hydroxide ion and phenoxide ion with 4-nitrophenyl esters of substituted benzoic acids in 10% acetonitrile-water (v/v) solution obey Hammett σ correlations. The values of the Hammett ρ of 1.67 (κArO) and 2.14 (κOH) are consistent with a large change in hybridization at the central carbon by comparison with the ρ value for a standard reaction where a full sp2 to sp3 change occurs. The transition state for the concerted reaction thus has a substantially tetrahedral geometry. The observation of the anti-Hammond effect whereby the ρ value for the hydroxide ion exceeds that of the less reactive phenoxide ion is consistent with a concerted, ANDN, mechanism for these reactions. A stepwise mechanism, AN + DN, is unlikely to yield a measurable break in the Hammett correlation for a change in the benzoyl substituent if the partitioning of the putative tetrahedral intermediate involves forward and reverse reactions with Hammett correlations possessing similar ρ values.
- Colthurst, Matthew J.,Williams, Andrew
-
p. 1493 - 1497
(2007/10/03)
-
- Imidazole-Catalyzed Hydrolysis of Substituted Benzoate Esters. A Detailed Kinetic and Mechanistic Study
-
Kinetic and mechanistic details of the imidazole-catalyzed hydrolysis of substituted phenyl benzoates in 10percent acetonitrile in water (V/V) were examined.The following 4 ester series were studied: p-nitrophenyl p-X-benzoates (X = CH3, H, Cl, CN, NO2, series I), p-Y-phenyl p-nitrobenzoates (Y = CH3, H, Cl, CN, NO2, series II), 2,4-dinitrophenyl p-X-benzoates (X = CH3O, H, Cl, CN, NO2, series III) and p-Y-phenyl 2,4-dinitrobenzoates (Y = CH3, H, Cl, CN, NO2, series IV).Based on: catalytic rate constants, activation parameters, kinetic solvent isotope effects, Hammett (ρ) values and the spectroscopic detection of the reaction intermediates, the following conclusions were reached: a) imidazole acts as a nucleophilic catalyst, i.e., the hydrolysis occurs via the intermediate formation of acylimidazole; b) the leaving group is the phenoxide ion; c) the rate limiting step is the decomposition of the tetrahedral intermediate that precedes the acylimidazole (series I, II and IV) or the attack of imidazole on the acyl group of the ester (series III). Keywords: Acylimidazoles / Catalysis / Chemical Kinetics / Isotope Effects / Reaction Mechanism
- Menegheli, Paulo,Farah, Joao P. S.,Seoud, Omar A. El
-
p. 1610 - 1615
(2007/10/02)
-
- A Simple and Mild Esterification Method for Carboxylic Acids Using Mixed Carboxylic-Carbonic Anhydrides
-
A simple and mild esterification method using mixed carboxylic-carbonic anhydrides has been developed.Simple aliphatic carboxylic esters are prepared in high yields by the reaction of acids with equimolar amounts of chloroformates (2,2,2-trichloroethyl chloroformate is an exception) and triethylamine in the presence of a catalytic amount of 4-(dimethylamino)pyridine.Although aromatic acids give a mixture of the ester, the acid anhydride, and the carbonate under normal conditions utilized in this study, it is found that increasing the amount of 4-(dimethylamino)pyridine drastically decreases the formation of the acid anhydride and the carbonate, affording a satisfactory yield of the ester.This method reaches a limit with sterically hindered acids and the formation of the acid anhydride and the carbonate is favored.
- Kim, Sunggak,Lee, Jae In,Kim, Youn Chul
-
p. 560 - 565
(2007/10/02)
-
- The Reactivity of p-Nitrophenyl Esters with Surfactants in Apolar Solvents. VII. Substituent Effects on the Reactivity of 4'-Nitrophenyl 4-Substituted Benzoates in Benzene Solutions of Dodecylammonium Propionate and Butane-1,4-diamine Bis(dodecanoate)
-
The rate of decomposition of a series of 4'-nitrophenyl 4-substituted benzoates has been measured at 341 K in benzene solutions of dodecylammonium propionate and butane-1,4-diamine bis(dodecanoate).The bimolecular rate constant due to general acid-general
- O'Connor, Charmian J.,Lomax, Terence D.
-
p. 917 - 925
(2007/10/02)
-