Alkyl Amides Research Articles

Two competing reactions of tetrabutylammonium alginate in organic solvents: Amidation versus γ-lactone synthesis

Biocompatibility and thickening properties predetermine alginates as ingredients in food, cosmetic and pharmaceutical products. Further chemical modifications are often desired for a product optimization. The introduction of hydrophobic groups can be realized by employing organic tetrabutylammonium alginate (TBA-Alg) solutions. The synthesis of alginic acid alkyl amides from TBA-Alg with 2-chloro-1-methylpyridinium iodide (CMPI) as a coupling agent, however, has so far not resulted in a high degree of amidation. The analysis of the coupling reaction revealed the formation of mannuronic acid γ-lactone structures, which required a conformation change from 1C4 to 4C1. The opening of the γ-lactone required a high excess of butylamine. In the case of CMPI, triethylamine had to be added prior to the coupling agent in order to suppress the assumed alginic acid formation. The degrees of amidation achieved were up to 0.8, and for propylphosphonic anhydride as the coupling agent up to 1. The molecular weights of the alginic acid butyl amide were ≥35kDa.

Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylation and Transcriptional Activity.

Signal transducer and activator of transcription 6 (STAT6) transmits signals from cytokines IL-4 and IL-13 and is activated in allergic airway disease. We are developing phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyrosine residues on IL-4 or IL-13 receptors and subsequent Tyr641 phosphorylation to inhibit the expression of genes contributing to asthma. Structure-affinity relationship studies showed that phosphopeptides based on Tyr631 from IL-4Rα bind with weak affinity to STAT6, whereas replacing the pY+3 residue with simple aryl and alkyl amides resulted in affinities in the mid to low nM range. A set of phosphatase-stable, cell-permeable prodrug analogues inhibited cytokine-stimulated STAT6 phosphorylation in both Beas-2B human airway cells and primary mouse T-lymphocytes at concentrations as low as 100 nM. IL-13-stimulated expression of CCL26 (eotaxin-3) was inhibited in a dose-dependent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcriptional activity of STAT6.

Simple route for nano-hydroxyapatite properties expansion

Simple surface modification of nano-hydroxyapatite, through acid-basic reactions, allows expanding the properties of this material. Introduction of organic groups such as hydrophobic alkyl chains, carboxylic acid, and amide or amine basic groups on the hydroxyapatite surface systematically change the polarity, surface area, and reactivity of hydroxyapatite without modifying its phase. Physical and chemical properties of the new derivative particles were analyzed. The biocompatibility of modified Nano-Hap on Raw 264.7 cells was also assessed.

Ligand-Enabled Meta-C-H Alkylation and Arylation Using a Modified Norbornene.

2-Carbomethoxynorbornene is identified as a more effective transient mediator to promote a Pd(II)-catalyzed meta-C(sp(2))-H alkylation of amides with various alkyl iodides as well as arylation with previously incompatible aryl iodides. The use of a tailor-made quinoline ligand is also crucial for this reaction to proceed.

ChemInform Abstract: Expedient Synthesis of Benzimidazoles Using Amides.

AbstractThe synthesis of benzimidazoles starting from substituted phenylen‐1,2‐diamines and N,N‐dimethylformamide, aryl or alkyl amides is performed under conventional heating as well as heating under microwave irradiation with the latter providing higher product yields after shorter reaction times.

Micelle Formation in Liquid Ammonia.

Perfluorinated long chain alkyl amides aggregate in liquid ammonia with increasing concentration which reflects micelle-type formation based on changes in (19)F NMR chemical shifts. The critical micelle concentrations (cmc) decrease with increasing chain length and give Kleven parameters A = 0.18 and B = 0.19. The micelles catalyze the ammonolysis of esters in liquid ammonia. The corresponding perfluorinated long chain alkyl carboxylates form ion pairs in liquid ammonia, but the equilibrium dissociation constants indicate favorable interactions between the chains in addition to the electrostatic forces. These perfluorinated carboxylates form micelles in aqueous solution, and their cmc's generate a Kleven B-value = 0.52 compared with 0.30 for the analogous alkyl carboxylates. The differences in hydrophobicity of CH2 and CF2 units in water and liquid ammonia are discussed, as is the possible relevance to life forms in liquid ammonia.

ChemInform Abstract: Mild and Selective Et2Zn‐Catalyzed Reduction of Tertiary Amides under Hydrosilylation Conditions.

AbstractA range of tertiary aryl, hetaryl, and alkyl amides equipped with a variety of functional groups is reduced in good to excellent yields.

Iron-Catalyzed Directed C(sp(2))-H and C(sp(3))-H Functionalization with Trimethylaluminum.

Conversion of a C(sp(2))-H or C(sp(3))-H bond to the corresponding C-Me bond can be achieved by using AlMe3 or its air-stable diamine complex in the presence of catalytic amounts of an inorganic iron(III) salt and a diphosphine along with 2,3-dichlorobutane as a stoichiometric oxidant. The reaction is applicable to a variety of amide substrates bearing a picolinoyl or 8-aminoquinolyl directing group, enabling methylation of a variety of (hetero)aryl, alkenyl, and alkyl amides. The use of the mild aluminum reagent prevents undesired reduction of iron and allows the reaction to proceed with catalyst turnover numbers as high as 6500.

ChemInform Abstract: Consecutive Three‐Component Synthesis of (Hetero)arylated Propargyl Amides by Chemoenzymatic Aminolysis—Sonogashira Coupling Sequence.

AbstractThe reaction provides access to N‐hetarylpropargyl and N‐arylpropargyl alkyl, alkenyl, alkynyl, benzyl and hetaryl amides endowed with a variety of functional groups.

Синтез, антихолинэстеразная и антибактериальная активность диалкиламиноалкиламидов <i>N</i>-ароил-α-аминоакриловой кислоты

Осуществлен синтез и описаны физико-химические характеристики 2-(диалкиламино)алкиламидов N-ароил-α-аминоакриловой кислоты и их четвертичных аммониевых солей. Приведены результаты изучения их взаимодействия с эритроцитарной ацетилхолинэстеразой (АХЭ) и плазменной бутирилхолинэстеразой (БуХЭ) человека. Для всех синтезированных соединений определены значения ИК50 (ингибирующая концентрация исследуемого соединения, при которой наблюдается 50 % торможение скорости холинэстеразного гидролиза 0,1 мМ ацетилтиохолина). Согласно полученным данным все синтезированные вещества проявляют антихолинэстеразные свойства и, в основном, специфичны по отношению к БуХЭ. Приведены также данные антибактериальных свойств синтезированных соединений.

ChemInform Abstract: Ligand‐Promoted Alkylation of C(sp3)—H and C(sp2)—H Bonds.

9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp3)–H and C(sp2)–H alkylation of simple amides with various alkyl iodides. This alkylation reaction was applied to the preparation of unnatural amino acids and geometrically controlled tri- and tetrasubstituted acrylic acids.

ChemInform Abstract: Synthesis of Nitriles via Palladium‐Catalyzed Water Shuffling from Amides to Acetonitrile.

AbstractTwo different procedures for the dehydration of either α,β,γ,δ‐unsaturated and cinnamoylamides or alkyl and aryl amides, respectively, to the corresponding nitriles are developed which tolerate multiple functional groups.

Hydrolysis of amphenicol and macrolide antibiotics: Chloramphenicol, florfenicol, spiramycin, and tylosin

Antibiotics that enter the environment can present human and ecological health risks. An understanding of antibiotic hydrolysis rates is important for predicting their environmental persistence as biologically active contaminants. In this study, hydrolysis rates and Arrhenius constants were determined as a function of pH and temperature for two amphenicol (chloramphenicol and florfenicol) and two macrolide (spiramycin and tylosin) antibiotics. Antibiotic hydrolysis rates in pH 4–9 buffer solutions at 25°C, 50°C, and 60°C were quantified, and degradation products were characterized. All of the antibiotics tested remained stable and exhibited no observable hydrolysis under ambient conditions typical of aquatic ecosystems. Acid- and base-catalyzed hydrolysis occurred at elevated temperatures (50–60°C), and hydrolysis rates increased considerably below pH 5 and above pH 8. Hydrolysis rates also increased approximately 1.5- to 2.9-fold for each 10°C increase in temperature. Based on the degradation product masses found, the functional groups that underwent hydrolysis were alkyl fluoride, amide, and cyclic ester (lactone) moieties; some of the resultant degradation products may remain bioactive, but to a lesser extent than the parent compounds. The results of this research demonstrate that amphenicol and macrolide antibiotics persist in aquatic systems under ambient temperature and pH conditions typical of natural waters. Thus, these antibiotics may present a risk in aquatic ecosystems depending on the concentration present.

Formation of the steroidal C-25 chiral center via the asymmetric alkylation methodology.

A novel approach for the preparation of steroids containing a chiral center at C-25 is reported. The key stereochemistry inducing step was asymmetric alkylation of pseudoephenamine amides of steroidal C-26 acids. The reaction proceeded with high diastereoselectivity (dr > 99 : 1). The developed methodology was successfully applied to the synthesis of (25R)- and (25S)-cholestenoic acids as well as (25R)- and (25S)-26-hydroxy brassinolides.

Intermolecular sp3 C–H bond functionalization of alkyl amides as a new method for the one-pot synthesis of functional neo alkyl amides with remote functional groups

The one-pot, regioselective, remote functionalization of amides of octanoic acid [R2NCOC7H15, NR2=NH2, NEt2, NC4H8O, (morpholinyl)] via Csp3–H bond cleavage with CO and various nucleophiles (EtOH, iPrOH, CF3CH2OH, H(CF2)2CH2OH, C8H17SH, Et2NH, morpholine, furan, thiophene, and anisole) in the presence of the superelectrophilic complex, CBr4·2AlBr3 has been performed for the first time. This methodology provides access to new synthetically challenging and promising derivatives of amides with remote functional groups of neo-structure. The oxidative cyclization of octanamide into a six-membered cyclic amide with the C(Me)Et group adjacent to the heteroatom using CBr4·2AlBr3 has been demonstrated.

Amino acid-based squaramides for anion recognition

Eight receptors 1–8 comprising an l-lysine scaffold modified at N- and C-termini with aliphatic alkyl chains and N,N′-alkyl amides, respectively, and bearing squaramide moieties on the amino acid side chain were synthesised by a combination of solid- and solution-phase chemistries and shown to complex various anions in 0.5% H2O in dimethyl sulfoxide-d6 solution. All of the receptors were found to bind Cl− , AcO− and BzO− via hydrogen-bond or acid–base interactions with the squaramide protons; however, 1 was found to bind to via hydrogen bonds formed between the anion and both the squaramide and amide NH moieties. Moreover, modification of both the N- and C-termini of the amino acids with different alkyl substituents had a negligible effect on their anion-binding properties while simultaneously conferring lipophilicities in a range that is optimal for molecules to behave as ‘drug-like’ systems as defined by Lipinski's rule of five. The results of this study demonstrate the versatility of such amino acid receptors as building blocks in the field of anion recognition.

Bis amide-aromatic-ureas—highly effective hydro- and organogelator systems

A series of hydro- and organo-supergelators have been synthesised via coupling of simple bis aromatic-ureas via alkyl amide linkages. These bis amide-aromatic-ureas exhibited reduced critical gelator concentrations, improved gelator stability, mechanical and dye removal properties for potential use in water purification, in comparison to related bis aromatic-ureas. Systematic structure studies via variation of the bis amide-aromatic-urea linker length as well as functionalization of the terminal aromatic moieties have enabled control over the gel properties.

Ligand-promoted alkylation of C(sp3)-H and C(sp2)-H bonds.

9-Methylacridine was identified as a generally effective ligand to promote a Pd(II)-catalyzed C(sp3)–H and C(sp2)–H alkylation of simple amides with various alkyl iodides. This alkylation reaction was applied to the preparation of unnatural amino acids and geometrically controlled tri- and tetrasubstituted acrylic acids.

Mooreamide A: a cannabinomimetic lipid from the marine cyanobacterium Moorea bouillonii.

Bioassay-guided fractionation of a collection of Moorea bouillonii from Papua New Guinea led to the isolation of a new alkyl amide, mooreamide A (1), along with the cytotoxic apratoxins A-C and E. The planar structure of 1 was elucidated by NMR spectroscopy and mass spectrometry analysis. Structural homology between mooreamide A and the endogenous cannabinoid ligands, anandamide, and 2-arachidonoyl glycerol inspired its evaluation against the neuroreceptors CB(1) and CB(2). Mooreamide A was found to possess relatively potent and selective ligand binding activity to CB(1) (K(1) = 0.47 µM) versus CB(2) (K(1) > 25 µM). This represents the most potent marine-derived CB(1) ligand described to date and adds to the growing family of marine metabolites that exhibit cannabinomimetic activity.

ChemInform Abstract: Organocatalytic Approach for C(sp3)—H Bond Arylation, Alkylation, and Amidation of Isochromans under Facile Conditions.

A new catalytic approach for the synthesis of isochroman derivatives via direct C(sp3)–H bond arylation is described. The oxidation reaction with [bis(trifluoroacetoxy)iodo]benzene facilitates the regeneration of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in the C(sp3)–H bond arylation of isochroman. The reaction conditions can also be used for alkyl Grignard reagents and amides to afford the corresponding isochroman derivatives.