Amide-containing Compounds Research Articles

Rhodium(III)-Catalyzed Anti-Markovnikov Hydroamidation of Unactivated Alkenes Using Dioxazolones as Amidating Reagents.

The amide is one of the most prevalent functional groups in all of pharmaceuticals, and for this reason, reactions that introduce the amide moiety are of particular value. Intermolecular hydroamidation of alkenes remains an underexplored method for the synthesis of amide-containing compounds. The majority of hydroamidation procedures exhibit Markovnikov regioselectivity, while current methods for anti-Markovnikov hydroamidation are somewhat limited to activated alkene substrates or radical processes. Herein, we report a general method for the intermolecular anti-Markovnikov hydroamidation of unactivated alkenes under mild conditions, utilizing Rh(III) catalysis in conjunction with dioxazolone amidating reagents and isopropanol as an environmentally friendly hydride source. The reaction tolerates a wide range of functional groups and efficiently converts electron-deficient alkenes, styrenes, and 1,1-disubstituted alkenes, in addition to unactivated alkenes, to their corresponding linear amides. Mechanistic studies reveal a reversible rhodium hydride migratory insertion step, leading to exquisite selectivity for the anti-Markovnikov product.

Prospective Application of Two New Pyridine-Based Zinc (II) Amide Carboxylate in Management of Alzheimer's Disease: Synthesis, Characterization, Computational and in vitro Approaches.

BackgroundAlzheimer’s disease (AD) is a neurodegenerative illness described predominantly by dementia. Even though Alzheimer’s disease has been known for over a century, its origin remains a mystery, and researchers are exploring many therapy options, including the cholinesterase technique. A decreased acetylcholine ACh neurotransmitter level is believed to be among the important factors in the progression of Alzheimer’s disease.MethodsIn continuation of synthesizing potential anti-Alzheimer agents and known appreciative pharmacological potential of amide-containing compounds, this study presents the synthesis of two novel amide-based transition metal zinc (II) complexes, AAZ7 and AAZ8, attached with a heterocyclic pyridine ring, which was synthesized and characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, 1H_NMR, and 13C_NMR. FT-IR spectroscopic records showed the development of bidentate ligand as Δν value was decreased in both complexes when compared with the free ligand. Both of the synthesized complexes were analyzed for acetylcholinesterase and butyrylcholinesterase inhibitory potential along with the antioxidizing activity.ResultsImportantly, the complex of AAZ8 exhibited more potent activity giving IC50 values of 14 µg/mL and 18µg/mL as AChE and BChE cholinesterase inhibitors, respectively, when compared with standard positive control galantamine. Interestingly, AAZ8 also displayed promising antioxidant potential by showing IC50 values of 35 µg/mL for DPPH and 29 µg/mL for ABTS in comparison with positive control ascorbic acid.ConclusionHerein, we report two new amide carboxylate zinc (II) complexes which were potentially analyzed for various biological applications like acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory potentials, and antioxidant assays. Computational docking studies also simulated results to understand the interactions. Additionally, thermodynamic parameters utilizing molecular dynamic simulation were performed to determine the ligand protein stability and flexibility that supported the results. Studies have shown that these compounds have the potential to be good anti-Alzheimer candidates for future studies due to inhibition of cholinesterase enzymes and display of free radical scavenging potential against DPPH as well as ABTS free radicals.

Amide additives improve RDC measurements in polyacrylamide.

Residual dipolar couplings (RDCs) provide valuable NMR parameters that can be used for structural calculation and verification. Measuring RDCs requires aligning macromolecules using one of various types of alignment media. Of different alignment media options, stretched or compressed polyacrylamide gels are advantageous due to their chemical stability. However, polyacrylamide interacts with proteins and significantly broadens NMR resonances. In this study, we found that the amide-containing compounds asparagine, glutamine and propionamide improve spectral quality of proteins in polyacrylamide gel without significantly reducing the magnitude of RDC values. Moreover, we showed that propionamide is an attractive additive that increases protein solubility without interfering with protein stability, ligand binding or NMR pulse width, suggesting its potential applications for our NMR methods.

Aqueous solution behaviour and solubilisation properties of octadecyl cationic gemini surfactants and their comparison with their amide gemini analogues.

Gemini surfactants 18-s-18(Et), comprised of two ethylammonium headgroups and two alkyl tails with m = 18 carbon atoms with spacers of s = 4, 6, 8 and 10 linking the headgroups (alkanediyl-α,ω-bis(diethyloctadecylammonium bromides)), were obtained. Their aqueous solution behaviour, including adsorption at the interface and aggregation in solution, was followed by tensiometric, conductometric and spectroscopic methods. The critical micelle concentration (CMC) of the surfactants decreased with increasing spacer length. The size of 18-s-18(Et) aggregates formed at concentrations of 10 and 40 CMC measured by DLS varied with the elongation of the spacer. Visualisation of aggregated surfactant structures at 40 CMC by cryo-TEM evidenced the formation of different morphologies depending on spacer length. Gemini with s = 4 formed elongated, cylindrical micelles, while geminis of s = 6, 8 and 10 self-assembled into vesicles. The ability of the studied geminis to solubilise hydrophobic dye Sudan I in water was determined as a function of surfactant concentration, demonstrating their high efficiency. Results for 18-s-18(Et) geminis were compared with those previously obtained for their analogues containing an amide group placed between headgroups and tails. The significant impact of amide groups on the surface activity and aggregation properties of gemini surfactants was evidenced and is related to hydrogen-bond formation by amide-containing compounds.

One-Step Trimethylstannylation of Benzyl and Alkyl Halides.

Trialkylstannanes are good leaving groups that have been used for the formation of carbon-metal bonds to electrode surfaces for analyses of single-molecule conductivity. Here, we report the multistep synthesis of two amide-containing compounds that are of interest in studies of molecular rectifiers. Each molecule has two trimethylstannyl units, one linked by a methylene and the other by an ethylene group. To account for the very different reactivities of the parent halides, a new methodology for one-step trimethylstannylation was developed and optimized.

Regulations of Xenobiotics and Endobiotics on Carboxylesterases: A Comprehensive Review.

Carboxylesterases (CESs) play major roles in catalyzing the hydrolysis of a wide range of ester- and amide-containing compounds. CESs dominate both the biotransformation of numerous therapeutic drugs and the detoxification of environmental toxicants, and the activity alteration of CESs may be a determinant reason for modification of the resultant pharmacokinetic/pharmacodynamic profile when two or more drugs are concurrently used. Herein, we provide a comprehensive review of the current literature involving of induction and inhibition on CESs by both exogenous and endogenous compounds. In particular, the inhibition constant and inhibition pattern of inhibitors on CESs in studies using animal microsomes or human recombinant CESs are summarized. Further studies are needed to clarify the underlying regulation mechanism, and alterations in CESs activity should be taken into consideration for safe clinical therapy.

Synthesis, structural aspects, and antimicrobial activity investigation of novel macrocyclic amide-containing compounds

Macrocyclic 16,76-dimethyl-1,7(2,4)-ditriazina-2,6,8,12-tetraaza-3,5,9,11-tetraoxocyclododecaphane, 16,86-dimethyl-1,8(2,4)-ditriazina-2,7,9,14-tetraaza-3,6,10,13-tetraoxocyclotetradecaphane, 16,96-dimethyl-1,9(2,4)-ditriazina-2,8,10,16-tetraaza-3,7,11,15-tetraoxocyclohexadecaphane, and 16,106-dimethyl-1,10(2,4)-ditriazina-2,9,11,18-tetraaza-3,8,12,17-tetraoxocyclooctadecaphane are synthesized. The compounds are characterized by elemental analyses, Raman, IR, 1H, 13C NMR and mass spectral data. The antimicrobial activities of the compounds are evaluated against several bacteria and yeast cultures and the results were compared with those of commercial antibiotic and antifungal agents. Structure–activity relationships are also discussed.

Structure-Based Interpretation of Biotransformation Pathways of Amide-Containing Compounds in Sludge-Seeded Bioreactors

Partial microbial degradation of xenobiotic compounds in wastewater treatment plants (WWTPs) results in the formation of transformation products, which have been shown to be released and detectable in surface waters. Rule-based systems to predict the structures of microbial transformation products often fail to discriminate between alternate transformation pathways because structural influences on enzyme-catalyzed reactions in complex environmental systems are not well understood. The amide functional group is one such common substructure of xenobiotic compounds that may be transformed through alternate transformation pathways. The objective of this work was to generate a self-consistent set of biotransformation data for amide-containing compounds and to develop a metabolic logic that describes the preferred biotransformation pathways of these compounds as a function of structural and electronic descriptors. We generated transformation products of 30 amide-containing compounds in sludge-seeded bioreactors and identified them by means of HPLC-linear ion trap-orbitrap mass spectrometry. Observed biotransformation reactions included amide hydrolysis and N-dealkylation, hydroxylation, oxidation, ester hydrolysis, dehalogenation, nitro reduction, and glutathione conjugation. Structure-based interpretation of the results allowed for identification of preferences in biotransformation pathways of amides: primary amides hydrolyzed rapidly; secondary amides hydrolyzed at rates influenced by steric effects; tertiary amides were N-dealkylated unless specific structural moieties were present that supported other more readily enzyme-catalyzed reactions. The results allowed for the derivation of a metabolic logic that could be used to refine rule-based biotransformation pathway prediction systems to more specifically predict biotransformations of amide-containing compounds.

NEW ROUTE TO AMIDE FORMATION

A NEW REACTION that uses an atypical starting material to create amide linkages could make it easier to prepare peptides and other amide-containing compounds that have been difficult to make until ...

Synthesis and reactivity of neodymium(III) amido-tethered N-heterocyclic carbene complexes

Abstract The reaction of the heteroleptic Nd(III) iodide, [Nd(L′)(N″)(μ-I)] with the potassium salts of primary aryl amides [KN(H)Ar′] or [KN(H)Ar ∗ ] affords heteroleptic, structurally characterised, low-coordinate neodymium amides [Nd(L′)(N″)(N(H)Ar′)] and [Nd(L′)(N″)(N(H)Ar ∗ )] cleanly (L′ = t- BuNCH 2 CH 2 [C{NC(SiMe 3 )CHN t- Bu}], N″ = N(SiMe 3 ) 2 , Ar′ = 2,6-Dipp 2 C 6 H 3 , Dipp = 2,6-Pr i 2 C 6 H 3 , Ar ∗ = 2,6-(2,4,6-Pr i 3 C 6 H 2 ) 2 C 6 H 3 ). The potassium terphenyl primary amide [KN(H)Ar ∗ ] is readily prepared and isolated, and structurally characterised. Treatment of these primary amide-containing compounds with alkali metal alkyl salts results in ligand exchange to give alkali metal primary amides and intractable heteroleptic Nd(III) alkyl compounds of the form [Nd(L′)(N″)(R)] (R = CH 2 SiMe 3 , Me). Attempted deprotonation of the Nd-bound primary amide in [Nd(L′)(N″)(N(H)Ar ∗ )] with the less nucleophilic phosphazene superbase Bu t N P{N P(NMe 2 ) 3 } 3 resulted in indiscriminate deprotonations of peripheral ligand CH groups.

Nylon-Nanotube Fibers

One potential application of carbon nanotubes is as a reinforcing agent for polymer fibers, and direct mixing has led to some significant improvements in tensile strength and Young's modulus. However, incomplete dispersion of the nanotubes, which tend to bundle together, and a lack of direct bonding to the polymer, which helps prevent pullout, have limited performance. Gao et al. have overcome some of these difficulties by using caprolactam as both solvent and monomer for incorporating single-walled nanotubes (SWNTs) into a nylon-6 matrix. Nitric acid-treated SWNTs, which are terminated with carboxylic acid groups, are well solvated by amide-containing compounds such as caprolactam. After nylon-6 is formed by the ring-opening polymerization of caprolactam, the amino end of the nylon chain can couple to the SWNTs via an amide linkage. The tensile strength and Young's modulus of nylon-6 improved by about a factor of 2 to 3 for SWNT loadings of 0.5 to 1.5 weight %. — PDS

Sphingosine 1-Phosphate Analogs as Receptor Antagonists

Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator that evokes a variety of cell and tissue responses via a set of cell surface receptors. The recent development of S1P receptor agonists, led by the immunomodulatory pro-drug FTY720, has revealed that S1P signaling is an important regulator of lymphocyte trafficking. With the twin goals of understanding structure-activity relationships of S1P ligands and developing tool compounds to explore S1P biology, we synthesized and tested numerous S1P analogs. We report herein that a subset of our aryl amide-containing compounds are antagonists at the S1P(1) and S1P(3) receptors. The lead compound in series, VPC23019, was found in broken cell and whole cell assays to behave as a competitive antagonist at the S1P(1) and S1P(3) receptors. The structure-activity relationship of this series is steep; for example, a slight modification of the lead compound resulted in VPC25239, which was one log order more potent at the S1P(3) receptor. These new chemical entities will enable further understanding of S1P signaling and provide leads for further S1P receptor antagonist development.

A comparison of amide and ureide nitrogen sources in tissue culture of tree legume Prosopis alba clone B2 V50

The effects of medium nitrogen sources on the recalcitrant nature of Prosopis alba clone B2V50 in tissue culture were compared involving shoot development using axillary bud explants from 2 to 4-year-old greenhouse-grown trees. A significant difference (P<0.05) was found between the amino acids aspartic acid and glutamic acid and their corresponding amide-containing compounds asparagine and glutamine. A comparison between amide and ureide nitrogen sources showed that allantoin, a ureide, was an acceptable replacement for asparagine or glutamine. Allantoin, asparagine, and glutamine could be used as the sole nitrogen sources. Allantoin at a concentration of 20 mM was adopted for use in future research. Although shoots were consistently induced, all explants showed complete shoot-tip necrosis after 12 weeks of in vitro culture.