Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMIDES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,189 records · Page 66Linked to original sources
PubMed2005

Highly stereoselective synthesis of (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated esters and (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated amides from 1-bromo-1-fluoroalkenes via palladium-catalyzed carbonylation reactions.

The highly stereoselective synthesis of (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated esters and (E)- and (Z)-alpha-fluoro-alpha,beta-unsaturated amides is described. 1-Bromo-1-fluoroalkenes (E/Z approximately 1:1), which are readily available starting materials, have been found to isomerize to high E/Z ratios after storage at -20 degrees C for 1 week or by photolysis at 254 nm. Since the (E)-isomers have been found to react faster than the corresponding (Z)-isomers at room temperature in Pd(0)-catalyzed reactions, the palladium-catalyzed carboalkoxylation of high E/Z 1-bromo-1-fluoroalkenes lead to a high Z/E (Z/E >/= 98:2) ratio of the alpha-fluoro-alpha,beta-unsaturated esters. When 1-bromo-1-fluoroalkenes (E/Z approximately 1:1) were reacted with HCOOH/NBu(3)/Pd(II)/DMF, the (E)-isomer was selectively reduced, and the remaining (Z)-1-bromo-1-fluoroalkenes were recovered in essentially pure isomeric form. The resulting mixture of (Z)-1-bromo-1-fluoroalkenes and the reduced products underwent similar palladium-catalyzed carboalkoxylation reactions at 70 degrees C, and the (E)-alpha-fluoro-alpha,beta-unsaturated esters were stereospecifically obtained. This methodology was also successfully applied for the stereospecific synthesis of (Z)- and (E)-alpha-fluoro-alpha,beta-unsaturated amides: the palladium-catalyzed carboamidation reaction of high E/Z and (Z)-1-bromo-1-fluoroalkenes lead to pure (Z)- and (E)-alpha-fluoro-alpha,beta-unsaturated amides, respectively.

Journal Article↗
PubMed2006

Pd-catalyzed amidation of 2-chloro- and 2,7-dichloro-1,8-naphthyridines.

[reactions: see text] The catalytic amidation between 2-chloro- and 2,7-dichloro-1,8-naphthyridines and primary amides bearing functional groups is reported. When Pd(OAc)2, xantphos, and K2CO3 are used, it is possible to obtain symmetric as well as nonsymmetric 2,7-diamido-1,8-naphthyridines in 50-90% yield with good functional-group tolerance. Monoamidation of 2,7-dichloro-1,8-naphthyridine using 0.9 equiv of the amide proceeded with good selectivity compared to the formation of the diamide, but as a result of the difficult isolation of the product, isolated yields were poor to moderate (22-42%).

Journal Article↗
PubMed2006

Conformation of N(alpha)-substituted hydrazino acetamides in CDCl3, the precious help of the analysis of Deltadelta between amidic hydrogens, and correlation to the conformation of aza-beta3-peptides.

[structures: see text] We studied the conformation of a series of primary amides in a solution of chloroform. Classical NMR tools such as dilution experiments, influence of DMSO, and 2D-NOESY, together with X-ray diffraction, were combined with an analysis of the difference of the chemical shift Deltadelta between the geminal amidic protons. This study was addressed in order to understand the conformation adopted by hydrazino acetamides 1a and 1b as model compounds for aza-beta3-peptides. In this manner, it was possible to show that the amidic group of these compounds acts as a H-bond donor and interacts with two different H-bond acceptors. We concluded that the hydrazinoturn, a specific bifurcated H-bond system observed in the solid state, is also the preferred conformation of hydrazino acetamides 1a and 1b in solution. Our results show that the short-range interaction with the N(alpha)-nitrogen lone pair not only stabilizes the C8 pseudocycle but could also contribute to the folding process of aza-beta3-peptides. In light of this, it could explain why aza-beta3-peptides develop a different H-bond network in comparison to their isosteric beta3-peptides analogues. Our work is in keeping with the recent interest of hydrazino peptides as an extension of the beta-peptide concept.

Acetamides↗
PubMed1996

Synthetic Applications of the beta-Lithiation of beta-Aryl Secondary Amides: Diastereoselective and Enantioselective Substitutions.

The sequence of beta-lithiation and electrophilic substitution of beta-aryl secondary amides is reported. The lithiations occur regioselectively at the beta-position, and the resulting lithiated intermediates can be reacted with a wide range of electrophiles to give substituted products. Reactions of beta-lithiated amides bearing an alpha-substituent provide substituted products with high diastereoselectivity. Electrophilic substitutions of beta-lithiated N-methylamides in the presence of the chiral diamine (-)-sparteine provide highly enantioenriched products. The methodology is used to synthesize enantioenriched beta-aryl beta-substituted amides, acids, and lactones.

Journal Article↗
PubMed1997

Enhanced Carboxylate Binding Using Urea and Amide-Based Receptors with Internal Lewis Acid Coordination: A Cooperative Polarization Effect.

A structural design strategy is described that greatly improves the acetate binding ability of neutral urea and amide-based receptors. The enhanced binding is due to a cooperative polarization effect which is induced by intramolecular coordination of the urea or amide carbonyl to a Lewis acidic boronate group. A series of boronate-ureas, 3, and a related bis(boronate-amide), 23, were prepared in two steps from 2-(aminophenyl)boronic acid and their structures elucidated using X-ray crystallography and other spectrometric methods. The abilities of the receptors to associate with tetrabutylammonium acetate in dimethyl sulfoxide solution were determined by (1)H NMR titration experiments. Association constants were calculated using nonlinear curve-fitting methods. The boronate-ureas 3 strongly bind to acetate in dimethyl sulfoxide solution with association constants as high as 6 x 10(4) M(-)(1). This is more than 150 times greater than the association constants for control urea receptors that lacked an appropriate boron substituent. Thermodynamic studies indicate that the enhanced association is due to a favorable enthalpic change. Additional NMR studies eliminated the possibility of proton transfer to the acetate during complex formation. Molecular modeling indicates that the boronate-ureas exhibit improved acetate binding because the intramolecular coordination (i) induces a larger host dipole moment which strengthens the guest/host ion-dipole interaction, and (ii) increases the positive surface potential at the urea NH residues which strengthens short range Coulombic interactions with the anionic acetate. The observed association constants correlate better with calculated host dipole moments, suggesting that for the boronate-ureas described here this is the more influential factor controlling association.

Journal Article↗
PubMed1999

Amination of Bis(trimethylsilyl)-1,2-bisketene to Ketenyl Amides, Succinamides, and Polyamides: Preparative and Kinetic Studies.

The reaction of the bisketene (Me(3)SiC=C=O)(2) (1) with amines is facile and proceeds by two distinct steps forming first ketenylcarboxamides 3 and then succinamides 5. Successive reaction of 1 with two different amines gives mixed succinamides, while phenylhydrazine gives succinimide 7. The reactions of 1.8 equiv of 1 with 1,4-(H(2)NCH(2))(2)C(6)H(4) gives alpha,omega-bisketenyldiamide 13, while equivalent amounts of 1 and diamines gave polymeric amides. Mixed ester amides 8 are formed by sequential reaction of 1 with an alcohol, followed by an amine, or vice versa. Kinetic studies of the amination reaction of 1 with excess amines in CH(3)CN gave rate constants k(obs) for the formation of ketenylcarboxamides that were fit by the relationship k(obs) = k(a)[amine](2) + k(b)[amine](3). Further reaction of the n-butyl ketenylcarboxamide 3b with n-BuNH(2) to give the succinamide 5b was first order in [n-BuNH(2)], while the further reaction of the CF(3)CH(2) ketenylcarboxyamide 3c with CF(3)CH(2)NH(2) to form 5c was fit by the equation k(obs) = k(c)[amine](2)/(k(d)[amine] + 1). The reaction of 3b with CH(3)OH to form the ester amide 8a is strongly accelerated compared to CH(3)OH addition to the corresponding ketenyl ester and gives significant stereoselectivity for formation of erythro product, and both these effects, as well as the absence of higher order kinetic terms in the reaction of 3b with n-BuNH(2), may arise from coordination by the carboxamido group to the nucleophile.

Journal Article↗
PubMed2006

Theoretical study on the properties of linear and cyclic amides in gas phase and water solution.

The structural and energetic properties of a group of selected amides, of well-known importance for the design of efficient clathrate inhibitors, are calculated with Hartree-Fock and density functional theory, B3LYP, theoretical levels, and a 6-311++g** basis set in the gas phase and a water solution. The conformational behavior of the molecules is studied through the scanning of the torsional potential energy surfaces and by the analysis of the differences in the energetic and structural properties between the isomers. The properties of the amides in water solution are determined within a self-consistent reaction field approach with a polarizable continuum model that allows the calculation of the different contributions to the free energy of solvation. The calculated barriers to rotation are in good agreement with the available experimental data and the comparison of the gas and water results shows the strong effect of the solute polarization. The properties of different amide-water complexes are calculated and compared with available experimental information.

Journal Article↗
PubMed2006

Effect of the exchange of substituent position in an amide amphiphile on the monolayer characteristics.

The monolayer characteristics of two very similar amphiphiles, N-tridecyl-beta-hydroxypropionic acid amide (C13H27-NH-CO-C2H4OH; THPA) and N-(beta-hydroxyethyl)tridecanoic acid amide (C13H27-CO-NH-C2H4OH; HETA), the chemical structure of which is only changed by exchanging the position of the two substituents at the acid amide group, are compared. These small changes in the chemical structure give rise to large differences in the phase behavior of the HETA and THPA monolayers, as concluded from the differences in the surface pressure-area (pi-A) isotherms. Since both amphiphiles have the same alkyl chain length, the shift of the fluid/condensed phase transition pressure pi(c) to higher temperatures from THPA to HETA indicates a stronger polar character of the THPA headgroup. Considerable differences between the HETA and THPA monolayers also exist in the domain morphology, although, in both cases, six arms usually grow from a round center. The fractal-shaped HETA domains grow by tip splitting under the formation of numerous doubloons so that branching is considerably limited. This suggests a certain fluidity of the HETA condensed phase. The main differences of the domains result from the higher crystallinity. The starlike THPA domains have dendritic character and can form curved dendrites, which are partially two-dimensional twins due to the formation of dislocations in the two-dimensional lattice structure. In the case of HETA monolayers, the grazing incidence X-ray diffraction studies reveal a hexagonal packing of the alkyl chains oriented perpendicularly to the surface in an LS phase. In the case of THPA monolayers, an oblique lattice is formed. However, at low temperatures, a second phase transition between two condensed phases occurs that is demonstrated by an abrupt transition between two different oblique lattice structures at the surface pressure where a cusp in the pi-A isotherms occurs at T < 10 degrees C.

Journal Article↗
PubMed2006

Site-specific hydrogen-bonding interaction between N-acetylproline amide and protic solvent molecules: comparisons of IR and VCD measurements with MD simulations.

The effects of solute-solvent interactions on solution structures of small peptides have been paid a great deal of attention. To study the effect of hydrogen-bonding interactions on peptide solution structures, we measured the amide I IR and VCD spectra of N-acetylproline amide (AP) in various protic solvents, i.e., D2O, MeOD, EtOD, and PrOD, and directly compared them with theoretically simulated ones. The numbers of protic solvent molecules hydrogen-bonded to the two peptide bonds in the AP were quantitatively determined by carrying out the molecular dynamics (MD) simulations and then compared with the spectral analyses of the experimentally measured amide I bands. The two peptides in the AP have different propensities of forming H-bonds with protic solvent molecules, and the H-bond population distribution is found to be strongly site-specific and solvent-dependent. However, it is found that adoption of the polyproline II (PII) conformation by AP in protic solvents does not strongly depend on the hydrogen bond network-forming ability of protic solvents nor on the solvent polarity. We present a brief discussion on the validity as well as limitation of the currently available force field parameters used for the present MD simulation study.

Journal Article↗
PubMed2005

Simple and complex lattices of N-alkyl fatty acid amides on a highly oriented pyrolytic graphite surface.

STM investigations of three N-alkyl fatty acid amide molecules have been carried out to get information of their molecular arrangement on a highly oriented pyrolytic graphite surface. With variable positions of amide along the alkyl chain, complex lattices with different lattice constants were observed. Besides the lattices with a repeat unit matching one or two molecular lengths, a lattice with a repeat unit corresponding to three molecular lengths was found. In addition, the portion of different lattices depends on the length of the shorter alkyl chain. DFT-D calculations point to interactions of antiparallel oriented dipoles due to the amide group, which are distance dependent and thus larger for shorter N-alkyl chains.

Journal Article↗
PubMed2006

Mild and direct conversion of quinoline N-oxides to 2-amidoquinolines with primary amides.

[reaction: see text] A simple, one-pot procedure is described for the direct conversion of quinoline N-oxides to alpha-amidoquinolines with primary amides. This methodology is complimentary to the Abramovich reaction, which is limited to the introduction of secondary amides via imidoyl chlorides. Although reaction conditions are quite similar, omission of the base is key for successful reaction with primary amides, which were found not to proceed through the intermediacy of an imidoyl chloride but rather through an acyl isocyanate.

Journal Article↗
PubMed2006

The first example of isomeric solid amide and its enol.

[Structure: see text] The first example of a crystalline amide and its tautomeric enol was obtained for the amide MeNHCSCH(CN)CONHMe (8) and its enol MeNHCSC(CN)=C(OH)NHMe (9). Their X-ray structures were determined, and their structural features resemble those of other related amides and enols. No other example of a similar pair was obtained. In solution, both 8 and 9 and a small percentage of the isomeric enol of thioamide MeNHCOC(CN)=C(SH)NHMe (10) were obtained in solvent-dependent compositions, which are rapidly established.

Journal Article↗
PubMed2006

Carbocations in action. Design, synthesis, and evaluation of a highly acid-sensitive naphthalene-based backbone amide linker for solid-phase synthesis.

The design, synthesis, and properties of an extremely acid-labile backbone amide linker based on a regiospecifically substituted tetraalkoxy naphthaldehyde core are presented. This handle enables cleavage of peptide backbone amides (secondary amides) off a solid support using as little as 0.5% TFA in CH2Cl2. This proceeds without cleavage of tert-butyl ethers and tert-butyl esters. The design is based on a DFT study that predicted the most stabile alkoxy-substituted methyl naphthyl carbocation. [structure: see text]

Journal Article↗
PubMedDate not supplied

Linear poly(ethylene oxide)-based polyurethane hydrogels: polyurethane-ureas and polyurethane-amides.

Over the last 30 years, water-swellable and water-insoluble hydrogels have been extensively investigated and developed, leading to a large family of materials which have found uses in a wide range of biomedical applications. While hydrogels usually present a crosslinked structure, linear polyurethane-ureas (PUUs) based on poly(ethylene oxide) have been shown to be able to absorb and swell with aqueous media without dissolving. This behavior is due to the phase separated domain morphology, where hydrogen bonded urethane/urea hard segment domains are dispersed in a PEO soft segment domain. This work investigates the possibility of obtaining linear poly(ethylene oxide)-based polyurethane-amide (PUA) hydrogels using two amide diols as chain extenders, a mono amide diol (AD) and a diamide diol (DD), and a dicarboxylic acid (maleic acid, MA). Poly(ethylene oxide) based PUAs were obtained using a "one-shot" bulk polymerization technique. The chemicophysical characterization and water-solubility tests showed that these materials, while having molecular weights similar to the PUUs, do not possess sufficient phase separation, hydrogen bonding and hydrophobicity of the hard segment domains to exhibit hydrogel behavior. Crosslinked PUAs using maleic acid as chain extender show interesting hydrogel properties.

Journal Article↗
PubMedDate not supplied

Novel C-terminally amidated opioid peptide in human phaeochromocytoma tumour.

As has often been observed in hypothalamic releasing factors and gastrointestinal hormones, the carboxy-terminal amide structure is a unique feature of peptides exhibiting hormonal or physiological activities. Although a variety of opioid peptides have hitherto been identified, such a C-terminal amidated species has never before been discovered in mammals. Here we present the first identification of a novel opioid octapeptide with a C-terminal amide structure, henceforth designated as 'adrenorphin', in human phaeochromocytoma tumour derived from adrenal medulla. The complete amino acid sequence of adrenorphin was determined by microsequencing and corresponds to the sequence of the first eight amino acids of peptide E which is derived from proenkephalin A. Adrenorphin has also been identified chromatographically in normal human and bovine adrenal medulla. Adrenorphin exhibits potent opioid activity in guinea pig ileum assay, suggesting a specialized physiological function.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla.

Biologically active peptide hormones and neurotransmitters have been shown to be enzymatically liberated from larger, inactive precursor molecules by tissue-specific post-translational processing, particularly at the typical cleavage signals of paired basic residues. Subsequent N-terminal or C-terminal modifications may be of importance in regulating the biological activities of these peptides. C-terminal alpha-amidation is considered to be essential for the biological function of several non-opioid peptides. Here we present the isolation and structure of a novel C-terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla. Amidorphin and the recently isolated octapeptide metorphamide (adrenorphin) are the only endogenous opioid peptides in mammals known to possess a C-terminal amide group. The amino acid sequence of amidorphin corresponds to the sequence 104-129 of bovine proenkephalin A. Very high concentrations of amidorphin were detected in bovine adrenal medulla and in a further endocrinological system, the hypothalamic-neurohypophyseal axis. Amidorphin may therefore be considered to be a major gene product of the opioid peptide precursor proenkephalin A in these endocrine tissues.

Adrenal Medulla↗
PubMed2003

alpha-Keto amides as precursors to heterocycles--generation and cycloaddition reactions of piperazin-5-one nitrones.

alpha-Keto amides 10a,b, formed from reaction of pyruvic or benzoylformic acid with allyl amine are found to present as single rotameric forms whilst their tertiary amido analogues 10c, d present as two rotamers in solution at rt. The hydroxyimino derivatives 8 share the conformational characteristics of their parents. The geometrical make-up of the new alpha-amidooximes is seen to depend on the structure of the starting acid and on the degree of substitution of the amido group. The oxime 8a derived from pyruvic acid and allyl amine is formed solely as the (E)-isomer whilst its tertiary amido analogue 8c is formed as both (E)- and (Z)-isomers. Oximes derived from benzoylformic acid have the opposite selectivity with both geometrical isomers forming from the secondary amide 8b and only the (Z)-isomer from the tertiary amide 8d. With the exception of 8b all oximes were configurationally stable with (Z)-isomers reacting to form isoxazolopyrrolidinones 11--compounds with a relatively rare bicyclic nucleus and (E)-isomers cyclising to piperazin-5-one nitrones 1--ketopiperazine N-oxides have to date only appeared once in the literature. New nitrones were trapped with phenyl vinyl sulfone, dimethyl acetylenedicarboxylate and methyl propiolate yielding isoxazolidine and isoxazoline fused piperazinones 13, 15, 21 and 22. Cycloadducts from dimethyl acetylenedicarboxylate and 8a, b are thermally labile and their rearrangement provides a novel route to pyrrolopiperazinones 16. The structure of a representative isoxazolopyrrolidinone, 11c, and a 2,3-dihydroisoxazoline fused piperazinone, 21b, are unambiguously solved following x-ray structural analysis.

Journal Article↗
PubMed2005

Simple reporter gene-based assays for hairpin poly(amide) conjugate permeability and DNA-binding activity in living cells.

Hairpin poly(amide)s (HPs) are sequence specific DNA-binding compounds that have engendered considerable interest as potential pharmacological agents to manipulate the expression of specific genes. However, recent reports have indicated that the ability of HP conjugates to pass through cell membranes is sensitive to the cell type employed and the nature of the conjugate. Furthermore, while binding of HPs to DNA sequences in vitro is relatively well understood, packing of DNA into chromatin in living cells makes predicting the efficiency with which a given poly(amide) will bind its cognate site less certain. Previous methods to evaluate HP permeability and binding in vivo, while effective, are somewhat tedious and qualitative. We report here two related reporter gene-based assays that provide a more convenient and quantitative measure of poly(amide) permeability and DNA binding activity in living cells. We anticipate that these methods will complement existing tools and facilitate the development of HP conjugates with the desired biological activity.

Base Sequence↗