Activity Of Amides Research Articles

Facile Modifications at the C4 Position of Pyrimidine Nucleosides via In Situ Amide Activation with 1H‐Benzotriazol‐1‐yloxy‐tris(dimethyl‐amino)phosphonium Hexafluorophosphate

Two approaches for C4 modifications of silyl-protected thymidine, 2'-deoxyuridine, and 3'-azido-2',3'-dideoxythymidine (AZT) are described. In both, nucleoside amide activation with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and DBU yields O4 -(benzotriazol-1-yl) derivatives. These in situ-formed intermediates are reacted with various nucleophiles, resulting in C4 modifications. In the two-step, one-pot approach, the O4 -(benzotriazol-1-yl) nucleoside intermediates are initially produced by reactions of the nucleosides with BOP and DBU in THF. This step is fast and typically complete within 30 min. Subsequently, the O4 -(benzotriazol-1-yl) derivatives are reacted with nucleophiles, such as aliphatic and aromatic amines, thiols, and alcohols, under appropriate conditions. Workup, isolation, and purification lead to the desired C4-modified pyrimidine nucleosides in good to excellent yields. In the one-step approach, the nucleosides are reacted with BOP and DBU, in the presence of the nucleophile (only aliphatic and aromatic amines, and thiols have been tested). Where comparisons are possible, the one-step approach is generally superior. © 2019 by John Wiley & Sons, Inc.

Synthesis, insecticidal activity, and phytotoxicity of novel chiral amides.

The lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae), is an important pest of stored grains worldwide. Chemical control is the main method used to manage this pest, but the continuous use of insecticides can lead to the selection of resistant R. dominica strains. Thus, there is a constant demand for the development of new insecticide molecules. This study describes the synthesis of 14 chiral amides and evaluation of their insecticidal activity against R. dominica. Their phytotoxicity to wheat (Triticum sativum) seeds is also evaluated. In the screening assay, compounds 8i and 8j caused 100% and 87% mortality of R. dominica. These values did not differ from the mortality caused by Bifenthrin® (75%). Amide 8i presented similar toxicity (LD50 =27.98 µmol g-1 , CI95 =25.14-30.71) and speed of action (LT50 =22 h, CI95 =19.34-24.66) to amide 8j (LD50 =29.37 µmol g-1 , CI95 =27.43-31.09, and LT50 =19 h, CI95 =17.05-20.95) against the pest. Both amides inhibited less than 44% of wheat growth. Among the tested amides, only 8i and 8j were effective in R. dominica control and presented no considerable phytotoxicity towards wheat seeds. Therefore, these amides are promising as insecticides for the management of R. dominica. © 2018 Society of Chemical Industry.

Well-Defined Pre-Catalysts in Amide and Ester Bond Activation.

Over the past few decades, transition metal catalysis has witnessed a rapid and extensive development. The discovery and development of cross-coupling reactions is considered to be one of the most important advancements in the field of organic synthesis. The design and synthesis of well-defined and bench-stable transition metal pre-catalysts provide a significant improvement over the current catalytic systems in cross-coupling reactions, avoiding excess use of expensive ligands and harsh conditions for the synthesis of pharmaceuticals, agrochemicals and materials. Among various well-defined pre-catalysts, the use of Pd(II)-NHC, particularly, provided new avenues to expand the scope of cross-coupling reactions incorporating unreactive electrophiles, such as amides and esters. The strong σ-donation and tunable steric bulk of NHC ligands in Pd-NHC complexes facilitate oxidative addition and reductive elimination steps enabling the cross-coupling of broad range of amides and esters using facile conditions contrary to the arduous conditions employed under traditional catalytic conditions. Owing to the favorable catalytic activity of Pd-NHC catalysts, a tremendous progress was made in their utilization for cross-coupling reactions via selective acyl C–X (X=N, O) bond cleavage. This review highlights the recent advances made in the utilization of well-defined pre-catalysts for C–C and C–N bond forming reactions via selective amide and ester bond cleavage.

SYNTHESIS AND HERBICID ACTIVITY OF ARYLOXYACETIC ACIDS AND AMIDES OF ARYLOXY ACETIC ACIDS CONTAINING CYCLOACETAL FRAGMENT

The herbicidal activity of esters and amides based on commercially available phenoxy chlorides and 2,4-dichlorophenoxyacetic acids was studied. Esters of 2,2-methyl-4-hydroxymethyl-1,3-dioxolane, 5-ethyl-5-hydroxymethyl-1,3-dioxane and 1,3-dioxolan-4-ylmethanol and 1,3-dioxane-5 -ol (glycerin formulas), as well as amides containing gem-dichlorocyclopropane and 1,3-dioxolane fragments were obtained. The acid chlorides, 1,3-dioxacycloalkanes and secondary amines were prepared according to standard basic methods. Esters and amides were synthesized from these starting compounds in a short time and with a quantitative yield (more than 90%). As a result of the synthesis of a mixture of 1,3-dioxolan-4-ylmethyl phenylacetate and 1,3-dioxan-5-yl phenylacetate, the content of the 5-ring cyclic derivative over the 6-chain structure was predominant, which is obviously associated with greater activity in the esterification reaction of primary alcohol than secondary. The screening results showed that the activity relative to wheat of the 1,3-dioxalane ester of 2,4-dichlorophenoxyacetic acid is superior to the Octagon-Extra standard. With respect to peas, derivatives of 2,4-dichlorophenoxyacetic acid and 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane are close to the standard for inhibition of shoot mass. The results of N-benzyl-N-[(2,2-dichlorocyclopropyl) methyl] -2-phenoxyacetamide and N-[(2,2-dichlorocyclopropyl) methyl]-N-(1,3-dioxolan-4-ylmethyl)-2-phenoxyacetamide with respect to peas and wheat also showed a marked herbicidal effect, close in value to the reference one. The test results of synthesized benzamides on wheat showed that, at a concentration of 100 mg/l, the compounds act approximately the same as the reference preparation at a dose of 50 mg/l. The obtained results prove the prospects of creating herbicidal preparations based on phenoxy- chlorides and 2,4-dichlorophenoxyacetic acids containing 1,3-dioxacycloalkane fragments. Therefore, these objects are very attractive for further study and synthesis of biologically active compounds containing the above pharmacophore groups.

Organocatalytic Oxidative Functionalizations of Alkynes

AbstractThe catalytic oxidation of alkynes has traditionally belonged to the domain of transition metal catalysis. Recently, several promising organocatalytic methods have been developed, leading to selective oxidative transformations of alkynes. For example, ynamides, because of their electron‐rich alkynes, are ideal candidates for Brønsted acid‐catalysis. A closely related keteniminium intermediate could also be accessed via amide activation. A particularly interesting aspect in this regard is a facile access to umpolung enolates, which would enable novel disconnections with complementary selectivity to traditional methods.

Electrophilic Activation of Amides for the Preparation of Poly­substituted Pyrimidines

In this article we describe the straightforward synthesis of polysubstituted pyrimidines by electrophilic activation of secondary amides in the presence of alkynes. An unusual mechanistic detour leading to pyridine derivatives as products is also presented and briefly discussed.

Type IIA - Type IIB protein tyrosine kinase inhibitors hybridization as an efficient approach for potent multikinase inhibitor development: Design, synthesis, anti-proliferative activity, multikinase inhibitory activity and molecular modeling of novel indolinone-based ureides and amides

Pursuing on our efforts regarding development of novel multikinase inhibitors, herein we report the design and synthesis of novel 2-indolinone-based ureides 6a-u and amides 10a-j. In this work we adopt a hybridization strategy between type IIA PTK inhibitor (sorafenib) and type IIB PTK inhibitors (sunitinib and nintedanib). This was implemented via linking the indolinone core, in both sunitinib and nintedanib, which is well-fitted in the hinge region in the kinase domain front cleft and the biaryl urea extension, in sorafenib, which is accommodated in the gate area and the hydrophobic back pocket. Molecular docking of the designed hybrid compounds in VEGFR-2 and FGFR-1 active sites revealed, as planned, their ability to establish the binding interactions achieved by both original type IIA and type IIB inhibitors. The designed compounds were evaluated for their multikinase inhibitory activity towards VEGFR-2, PDGFR-b and FGFR-1 and anti-proliferative activity towards HepG2, MCF-7, A549 and A498 cancer cell lines. The ureido analogue 6u emerged as the most potent multikinase inhibitor in the ureido series with VEGFR-2, FGFR-1 and PDGFR-b IC50 of 0.18, 0.23 and 0.10 μM, respectively. Whereas, the amido congener 10j emerged as the most potent multikinase inhibitor in the amide series with VEGFR-2, FGFR-1 and PDGFR-b IC50 of 0.28, 0.46 and 0.09 μM, respectively. While, indolinone 6u was the most potent derivative towards HepG2 cells (IC50 = 2.67 ± 0.14 μM), 6r stood out as the most potent indolinone against A498 cells (IC50 = 0.78 ± 0.02 μM). Additionally, the target indolinones displayed non-significant cytotoxic impact towards human normal melanocyte (HFB4). ADME prediction study of the designed compounds showed that they are not only with promising multikinase inhibitory activity but also with favorable pharmacokinetic and drug-likeness properties. Compounds 6r and 10j are revealed to be the best compounds in terms of multikinase activity and pharmacokinetics.

Single-Step Synthesis of Nitrogen-Doped Porous Carbons for CO2 Capture by Low-Temperature Sodium Amide Activation of Petroleum Coke

In this work, highly efficient nitrogen-doped porous carbonaceous CO2 sorbents were synthesized by sodium amide activation of petroleum coke at a temperature range of 400–500 °C. The as-obtained so...

N-doped porous carbons from low-temperature and single-step sodium amide activation of carbonized water chestnut shell with excellent CO2 capture performance

The aim of this study is to exploit low-cost N-doped porous carbonaceous adsorbents with excellent CO2 adsorption properties. Herein, the N-enriched porous carbons were obtained through a single-step sodium amide activation of carbonized water chestnut shell at 400–500 °C. The optimal sample possesses high CO2 uptake of 4.50 mmol/g (25 °C) and 6.04 mmol/g (0 °C) at atmospheric pressure. Additionally, this sample displays high CO2/N2 selectivity, stable cyclic ability, moderate CO2 isosteric heat of adsorption, fast CO2 adsorption rate, and high dynamic CO2 uptake. In addition to the two well-known factors i.e. volume of narrow micropore and N content, the pore size distribution is also found to play major role in deciding CO2 adsorption performance for these adsorbents. The features of excellent CO2 adsorption properties, low-cost raw materials, low reaction temperature and facile preparation demonstrate that these adsorbents are prospective in the application of CO2 capture.

Amide Activation in Ground and Excited States.

Not all amide bonds are created equally. The purpose of the present paper is the reinterpretation of the amide group by means of two concepts: amidicity and carbonylicity. These concepts are meant to provide a new viewpoint in defining the stability and reactivity of amides. With the help of simple quantum-chemical calculations, practicing chemists can easily predict the outcome of a desired process. The main benefit of the concepts is their simplicity. They provide intuitive, but quasi-thermodynamic data, making them a practical rule of thumb for routine use. In the current paper we demonstrate the performance of our methods to describe the chemical character of an amide bond strength and the way of its activation methods. Examples include transamidation, acyl transfer and amide reductions. Also, the method is highly capable for simple interpretation of mechanisms for biological processes, such as protein splicing and drug mechanisms. Finally, we demonstrate how these methods can provide information about photo-activation of amides, through the examples of two caged neurotransmitter derivatives.

Cu42Ge24Na4—A Giant Trimetallic Sesquioxane Cage: Synthesis, Structure, and Catalytic Activity

Unprecedented germanium-based sesquioxane exhibits an extremely high nuclearity (Cu42Ge24Na4) and unusual encapsulation features. The compound demonstrated a high catalytic activity in the oxidative amidation of alcohols, with cost-effective catalyst loading down to 400 ppm of copper, and in the oxidation of cyclohexane and other alkanes with H2O2 in acetonitrile in the presence of nitric acid. Selectivity parameters and the mode of dependence of initial cyclohexane oxidation rate on initial concentration of the hydrocarbon indicate that the reaction occurs with the participation of hydroxyl radicals and alkyl hydroperoxides are formed as the main primary product. Alcohols have been transformed into the corresponding ketones by the catalytic oxidation with tert-butyl hydroperoxide.

Density Functional Studies on Secondary Amides: Role of Steric Factors in Cis/Trans Isomerization.

Cis/trans isomerization of amide bonds is a key step in a wide range of biological and synthetic processes. Occurring through C-N amide bond rotation, it also coincides with the activation of amides in enzymatic hydrolysis. In recently described QM studies of cis/trans isomerization in secondary amides using density functional methods, we highlighted that a peptidic prototype, such as glycylglycine methyl ester, can suitably represent the isomerization and complexities arising out of a larger molecular backbone, and can serve as the primary scaffold for model structures with different substitution patterns in order to assess and compare the steric effect of the substitution patterns. Here, we describe our theoretical assessment of such steric effects using tert-butyl as a representative bulky substitution. We analyze the geometries and relative stabilities of both trans and cis isomers, and effects on the cis/trans isomerization barrier. We also use the additivity principle to calculate absolute steric effects with a gradual increase in bulk. The study establishes that bulky substitutions significantly destabilize cis isomers and also increases the isomerization barrier, thereby synergistically hindering the cis/trans isomerization of secondary amides. These results provide a basis for the rationalization of kinetic and thermodynamic properties of peptides with potential applications in synthetic and medicinal chemistry.

Low-Temperature and Single-Step Synthesis of N-Doped Porous Carbons with a High CO2 Adsorption Performance by Sodium Amide Activation

In this study, N-enriched porous carbons were prepared by a facile synthesis method at low temperatures ranging from 400 to 500 °C. Sodium amide was used as both activator and nitridation reagent, ...

Origin of Nb2 O5 Lewis Acid Catalysis for Activation of Carboxylic Acids in the Presence of a Hard Base.

The Nb2O5 surface catalyzes the amidation of carboxylic acids with amines through Nb5+ Lewis acid activation of the C=O group. In this work, DFT calculations were applied to theoretically investigate the C=O bond activation of a model carboxylic acid (acetic acid) on θ‐Al2O3(110), anatase TiO2(101), and T‐Nb2O5(100) surfaces. The adsorption sites, adsorption energies, reaction energy barriers, electronic properties, and vibrational frequency of acetic acid were examined in detail. It was found that the bond activation of the carbonyl group is most efficient on Nb2O5, although the adsorption energy is larger on Al2O3 and TiO2. The most efficient C=O bond activation on Nb2O5 results in the lowest energy barrier of C−N bond formation during amidation. The Nb2O5 surface also shows larger tolerance to methylamine and water molecules than Al2O3 and TiO2 surfaces. These crucial factors contribute to the highest amidation catalytic reactivity on Nb2O5. Furthermore, the position of the mean density of states of the d‐conduction band of the active metal site relative to the Fermi energy level correlates well with the efficiency in the C=O bond activation and, consequently, the catalytic activity for amidation. These results suggest that, unlike a classical understanding of strong acid sites of metal oxide surfaces, interaction of a carbonyl HOMO with an unoccupied metal d‐orbital, or, in other words, covalent‐like interaction between a carbonyl group and metal adsorption site, is relevant to the present system.

Acetylcholinesterase inhibition and antimicrobial activity of hydroxyl amides synthesized from natural products derivatives.

Thirteen natural products derivatives of hydroxyl amide class, three described for the first time, were synthesized by reaction of three indole acids and 3,4,5-trimethoxybenzoic acid with six different amino alcohols in the presence of triphenylphosphine and N-bromosuccinimide. The derivatives were tested against the Gram (+) bacteria Staphylococcus aureus and Bacillus cereus, Gram (-) Pseudomonas aeruginosa and Escherichia coli, besides the yeast Candida albicans. One of the compounds (7) was selectively active against C. albicans (91.3 ± 0.49% inhibition) showing a great potential as a new drug lead, since it was more active than the positive control, miconazole (88.7 ± 2.41% inhibition). Regarding bacterial inhibition, compounds demonstrated mild activity, but inhibition of compounds 9, 10 and 13 towards E. coli is of interest since it is difficult to find drugs selectively active against Gram (-) bacteria. Most of the compounds were very active in the acetylcholinesterase inhibition assay. Compound 7 was again the most active (93.2 ± 4.47%), being more potent than the control galantamine (90.3 ± 0.45%). The most active gallic acid derivatives, compounds 3, 7 and 8 have in common, besides gallic acid skeleton, a (CH2)2OH group, which may be one of the structural requirements for AChE inhibition.

Biological activity of doubly modified salinomycin analogs – Evaluation in vitro and ex vivo

The polyether ionophore salinomycin has recently captured much interest due to its potent activity against multi-drug resistant cancer cells and cancer stem cells. Previous studies have shown that either acylation of the C20 position or esterification/amidation of the C1 carboxylate moiety is beneficial in terms of biological properties. In this paper, we present the first analogs combining such modifications. Evaluation of the anti-proliferative activity against a series of cancer cell lines showed that acylation of the C20 hydroxyl group improves the activity of salinomycin C1 amides but not of the corresponding C1 esters. Importantly, the activity of several of the doubly modified analogs surpasses that of commonly used cytostatic drugs cisplatin and doxorubicin in the LoVo/DX multi-drug resistant cell line. All analogs were tested against primary acute lymphoblastic leukemia cells in standard cell viability assays; three were more potent than salinomycin. Further studies revealed that selected analogs induced characteristics of apoptotic cell death and increased expression of p53. Additionally, using an ex vivo model of breast tumor, tumor cell viability significantly decreased after treatment with salinomycin or its double-modified derivative (3a) in a time-dependent manner. The present findings indicate that double-modified salinomycin derivatives constitute promising lead compounds for targeting various types of cancer.

Synthesis and Cytotoxic Activity of Amides from Isopimaric Acid

The amide derivatives were synthesized from isopimaric acid and characterized by spectroscopy. These amides were examined in vitro for their cytotoxic activity against four cancer cell lines. The majority of the screened compounds displayed better inhibitory activity than isopimaric acid, and many amides displayed promising cytotoxic activity against hepatocarcinoma (HepG-2), breast carcinoma (MDA-MB-231), and prostate adenocarcinoma (PC-3). It was found that the substituent type, number, and position in the benzene and heterocyclic rings have an important influence on cytotoxicity against the three tested cancer cell lines.

Synthesis and antimicrobial activities of novel sorbic and benzoic acid amide derivatives

A series of sorbic and benzoic acid amide derivatives were synthesized by conjugating sorbic acid (SAAD, a1–a7) or benzoic acid (BAAD b1–b6) with amino acid esters and their antimicrobial activities were investigated against Escherichia coli, Bacillus subtilis and Staphylococcus aureus, mixed bacteria from rancid milk, Saccharomyces cerevisiae, and Aspergillus niger. The antimicrobial activity of sorbic acid amides was better than that of benzoic acid amides. The minimum inhibitory concentrations (MIC) of compound isopropyl N-[1-oxo-2, 4-hexadien-1-yl]-L-phenylalaninate (a7) were 0.17 mM against B. subtilis, and 0.50 mM against S. aureus, while the MIC values of sorbic acid were more than 2 mM respectively. Also, compound a7 displayed pH-independent antimicrobial activity in the range of pH 5.0–9.0 and was effective at pH 9.0. These results demonstrated that the conjugation of sorbic acid with amino acid esters led to significant improvement of in vitro antimicrobial attributes, but little effect was observed for benzoic acid amide derivatives.

Selectfluor-mediated mono-C–H activation: The syntheses of mono-ortho-substituted anilides

The C–H activation of aryl amide using readily available Pd(OAc)2 in the presence of selectfluor is reported. The highly mono-selective introduction of sp2 hybridized functional groups have been realized. A broad range of aryl-, alkenyl- and keto-aryl amides were prepared using unactivated coupling partners under mild conditions.

Valorization of Adenanthera pavonina seeds as a potential biosorbent for lead and cadmium removal from single and binary contaminated system

This study investigated the biosorption of Pb (II) and Cd (II) on powdered seeds of Adenanthera pavonina from single and binary heavy metal solutions. The adsorption capacity of the metal ions was studied as a function of pH, adsorbent dose, initial metal ion concentration, and contact time. In the single heavy metal system, maximum removal of Pb (II) and Cd (II) were achieved at pH 4 and 6, respectively, while the equilibrium was attained at a contact duration of 35 min at a constant dose of 5 g L−1 was maintained for both Pb (II) and Cd (II). Further, the kinetic study revealed that the biosorption process was best described by the second-order kinetic model. In the competitive biosorption of binary mixtures of Pb (II) and Cd (II) were studied in terms of percentage removal of metal ions, adsorption capacity and equilibrium sorption isotherm. The percentage removal of metal ions in binary solutions was suppressed in presence of the other competitive metal ion. Field emission scanning electron microscopy integrated with energy dispersive X-ray spectroscopy of the biomass before (control) and after (metal loaded biomass) the biosoption process, confirmed the presence of respective heavy metal on to the biomass. Fourier transmission infrared spectroscopy spectra supported the activity of hydroxyl, amines, amides, and carboxyl groups in uptake of both heavy metal ions.