Stable Ester Research Articles

New banana-type liquid crystal with a methoxy group substituted near the central ring

A seven-ring achiral bent core (banana-shaped) mesogen with a thermally stable ester linkage in the molecule was synthesized. The novelty of the molecular structure lies in the methoxy group laterally substituted in the ortho position on the phenyl ring located near the molecular centre. The compound shows two mesophases; the high temperature one can be attributed to the antiferroelectric B2 phase, the low temperature one is a smectic phase with an in-plane ordering.

Self-assembled monolayers as the coating in a quartz piezoelectric crystal immunosensor to detect Salmonella in aqueous solution.

A new procedure based on the self-assembled monolayers (SAM) of alkanethiols was developed to immobilize antibodies onto gold electrodes of a quartz crystal microbalance (QCM) for detecting Salmonella paratyphi A. The procedure includes (1) chemisorption of 3-mercaptopropionic acid (MPA) at electrode surfaces to produce a carboxylic acid terminated monolayer, (2) activation by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydrosuccinimide (NHS) to generate a stable acyl amino ester intermediate, and (3) condensation of antibodies after aminolysis of the NHS adduct. Activation by two coupling agents (EDC and NHS) was shown to enhance the stability of the coating and facilitate the formation of a suitable intermediate to condense antibodies reproducibly and densely at the SAM, leading to high sensitivity and good precision of the developed immunosensor. With 50 min incubation under continuous monitoring, working ranges from 10(2) to 10(5) cells/mL with repeatability < 10% RSD were obtained. On the basis of S/N = 3, the detection limit was 1.7 x 10(2) cells/mL The MO2 piezoimmunosensor developed was specific to differentiate S. paratyphi A against Escherichia coli and other serogroups of Salmonella that are commonly present together.

The preparation of a new "safety catch" ester linker for solid-phase synthesis.

A new "safety catch" linker for esters has been synthesized on polystyrene resin. This 2-tert-butoxyphenol resin 10 may be acylated to give a relatively stable ester that will allow nucleophilic chemistry without reaction at the linking ester group. Removal of the tert-butyl group with acid unmasks a highly reactive 2-hydroxyphenyl ester that reacts readily with nucleophiles to cause release of the product from the resin. This sequence has been exemplified by acylating the resin with various bromo acids, carrying out nucleophilic displacements with thiols, phenols, or amines, activating the ester with trifluoroacetic acid and cleaving from the resin with amines to give the (nucleophile) substituted carboxamides in high yield and purity. Kinetic studies with a model ester revealed half-lives for reaction with morpholine of 119 h for the tert-butoxyphenyl ester and 1 min for the corresponding phenol.

Nickel-mediated alcoholysis reaction of carbon–nitrogen triple bond: structural characterization of an unprecedented moisture stable imido ester with an E-configuration

The X-ray structural characterization of a moisture stable imido ester with an E-configuration, obtained from the nickel(II)-mediated alcoholysis reaction of the nitrile group of a newly synthesized 6,7-dicyano-2,3-di(2-pyridyl) pyrazine compound ( L), is reported.

Thermo-oxidative studies of poly(ether-esters) 2. Copolymer of poly(butylene terephthalate) and polybutylene oxide

To determine the thermo-oxidative degradation mechanism of a copolymer of poly(butylene terephthalate) and polybutylene oxide, degradation experiments were carried out on this polymer and a model compound (dibutyleneglycol dibenzoate) at 140°C in an oxygen atmosphere. The changes were analysed using various analytical techniques, such as oxygen uptake measurements, measurement of CO/CO 2 formation, 1H and 13C NMR, FT-IR and GC–MS. On the basis of the results, an oxidation mechanism for the model compound was proposed and it was concluded that oxidation is initiated at the methylene carbon adjacent to the ether oxygen. The thermal oxidation mainly results in the formation of a stable ester together with a formate, aliphatic and aromatic acids and an alcohol. Based on the similar degradation products found for the model compound and the polymer, it was concluded that the thermo-oxidation mechanisms in these two compounds are similar.

Active-site variants of Streptomyces griseus protease B with peptide-ligation activity

Background: Peptide-ligating technologies facilitate a range of manipulations for the study of protein structure and function that are not possible using conventional genetic or mutagenic methods. To different extents, the currently available enzymatic and nonenzymatic methodologies are synthetically demanding, sequence-dependent and/or sensitive to denaturants. No single coupling method is universally applicable. Accordingly, new strategies for peptide ligation are sought.Results: Site-specific variants (Ser195→Gly, S195G, and Ser195→Ala, S195A) of Streptomyces griseus protease B (SGPB) were generated that efficiently catalyze peptide ligation (i.e., aminolysis of ester-, thioester- and para-nitroanilide-activated peptides). The variants also showed reduced hydrolytic activity relative to the wild-type enzyme. The ratio of aminolysis to hydrolysis was greater for the S195A variant, which was also capable of catalyzing ligation in concentrations of urea as high as 2 M.Conclusions: Mutagenic substitution of the active-site serine residue of SGPB by either glycine or alanine has created a unique class of peptide-ligating catalysts that are useful for coupling relatively stable ester- and para-nitroanilide-activated substrates. Ligation proceeds through an acyl–enzyme intermediate involving His57. Serine to alanine mutations may provide a general strategy for converting proteases with chymotrypsin-like protein folds into peptide-coupling enzymes.

Synthesis, structure and comparative stability of β-hydrazono, oximino methyl ether and imino boronates

β-Hydrazono and oximino ether boronates have been prepared by the sequential lithiation of the corresponding methyl hydrazone or oxime methyl ether, followed by reaction with an iodomethylboronate ester, typically in the form of the pinacol ester. The resulting products have contrasting hydrolytic stabilities. β-Hydrazono boronates are highly sensitive to intramolecularly catalysed hydrolysis, providing the corresponding β-keto boronates in generally high yields; β-oximino ether boronates are stable to silica gel chromatography and show evidence of E–Z-isomerisation. Stable homochiral boronate ester derivatives of β-oximino ethers can be readily prepared by a double transesterification process, via a diethanolamine-mediated pinacol ester exchange, followed by diethanolamine ester hydrolysis–reesterification process with a homochiral diol. β-Imino boronates can be generated in situ by condensation of the corresponding β-keto boronate with a primary amine, however the resulting imine function is highly hydrolytically unstable and cannot be isolated in a pure form.

Practical preparation and substitution of configurationally stable aziridinyl ester anions

Configurationally and chemically stable aziridine carboxylate anions have been generated. These intermediates are stable at −78°C for several hours and react with electrophiles with good to excellent retention of configuration.

An FTIR Study of Anhydride Formation on Heating Butane Tetracarboxylic Acid in the Presence of Various Catalysts

Polycarboxylic acids containing more than three carboxylic acid groups react with hydroxyl groups in cotton cellulose and crosslink cotton through stable ester bonds. The aim of this research is to use variable temperature diffuse reflectance infrared spectros copy to study anhydride formation from the thermal dehydration reaction of 1,2,3,4- butanetetracarboxylic acid (BTCA) in the presence of one of three catalysts—sodium carbonate, sodium hypophosphite, and cyanamide. An environmental chamber equipped with a temperature controller is attached to the infrared spectrometer to obtain diffuse reflectance spectra at elevated temperatures and ambient pressure. With this spectroscopic method, the temperature profile of anhydride formation from BTCA in the presence of a particular catalyst is clearly visible.

Rapid Liquid Chromatographic Assay of Vitamin E and Retinyl Palmitate in Extruded Weaning Foods

ABSTRACTExtruded weaning foods were produced using cowpea + corn + soybean + soybean oil (35:50:10:5, w/w) and cowpea + corn + peanut (42:43:15, w/w) by twin screw extrusion and fortified with vitamin premix. A direct solvent extraction method was used to assay fortified α‐tocopheryl acetate as the ester to differentiate it from the naturally occurring alcohol for accurate assessment of total vitamin E activity. The fortified retinyl palmitate was assayed from the same extraction and assayed as the more stable ester with the same LC conditions after changing the detection wavelengths. Using direct solvent extraction, analytical values of vitamin E homologs in extruded products were higher than those values from saponification.

N-[2,2-dimethyl-3-(N-(4-cyanobenzoyl)amino)nonanoyl]-L-phenylalanine ethyl ester as a stable ester-type inhibitor of chymotrypsin-like serine proteases: structural requirements for potent inhibition of alpha-chymotrypsin.

We introduce a new potent inhibitor, N-[2, 2-dimethyl-3-(N-(4-cyanobenzoyl)amino)nonanoyl]-L-phenylalanine ethyl ester (3), which preferentially inhibits serine proteases belonging to a chymotrypsin superfamily. This inhibitor, despite consisting of a stable ethyl ester structure, showed strong inhibitory activities toward bovine alpha-chymotrypsin, human cathepsin G, and porcine elastase by acting as an acylating agent. The calculated inactivation rate constant (kinact) and enzyme-inhibitor dissociation constant (Ki) against alpha-chymotrypsin were 0.0028 s-1 and 0.0045 microM, respectively (kinact/Ki = 630 000 M-1 s-1). These kinetic parameters indicate that this inhibitor is one of the most powerful alpha-chymotrypsin inactivators ever reported. On the basis of structure-activity relationship (SAR) and structure-stability relationship studies of analogues of 3, which were modified in three parts of the molecule, i.e., the 4-cyanophenyl group, beta-substituent at the beta-amino acid residue, and ester structure, we suggest that the potent inhibitory activity of 3 is due to the following structural features: (1) the ethyl ester which enforces specific acyl-enzyme formation, (2) the n-hexyl group at the beta-position and 4-cyanophenyl group which stabilize the acyl-enzyme, and (3) the phenylalanine residue which functions for the specific recognition of S1 site in the enzyme. In particular, the action of 3 as a potent inhibitor, but poor substrate, can be ascribed largely to the very slow deacylation rate depending on the structure factors cited in feature 2. The results of inhibition by 3 and its analogues against different serine proteases such as chymase, cathepsin G, and elastase suggest that these compounds recognize common parts in the active sites among these chymotrypsin-like serine proteases, and 3 is one of the most suitable structures to recognize those common parts. Our results provide an intriguing basis for further developments in the design of a stable ester-based selective serine protease inhibitor.

Synthesis and UV−Visible Properties of Soluble Regioregular Oligo(3-octylthiophenes), Monomer to Hexamer

A series of head to tail alkyl-substituted oligothiophenes was synthesized by a stepwise synthesis based on the repetitive use of the Suzuki coupling reaction between a stable thienyl boronic ester...

Synthesis of new d-propoxyphene derivatives and the development of a microparticle-based immunoassay for the detection of propoxyphene and norpropoxyphene

The synthesis of [S-(R,S)]-4-[[methyl[2-methyl-3-(1-oxopropoxy)-3, 4-diphenylbutyl]amino]-1-oxobutoxy]-2,5-pyrrolidinedione+ ++ (propoxyphene active ester, 2) is described. This was used as an intermediate to prepare a propoxyphene immunogen, [S-(R,S)]-4-[methyl][2-methyl-3-(1-oxopropoxy)-3,4-diphenylbuty l]-amino]- 1-oxobutyl-Bovine Thyroglobulin (3). This immunogen was then used to generate antibodies which demonstrate good cross-reactivity to d-propoxyphene, d-norpropoxyphene, and other propoxyphene metabolites. In addition, these antibodies were shown to have very low cross-reactivity to methadone, a structurally related compound. The introduction of an aminomethyl benzoate spacer into the propoxyphene active ester (2), followed by the activation of the carboxylic acid, provided for a more stable active ester (5). This stable active ester, together with the antibodies generated from the propoxyphene immunogen, has led to the development of an immunoassay based on the Kinetic Interaction of Microparticles in Solution (KIMS).

Characterization of Acridancarboxylic Acid Derivatives as Chemiluminescent Peroxidase Substrates

A new class of peroxidase substrates has been developed which produces chemiluminescence upon enzymatic oxidation. A wide variety of N-alkylacridancarboxylic acid derivatives including esters, thioesters, and sulfonamides are efficiently oxidized by a peroxidase and a peroxide to enzymatically produce the corresponding chemiluminescent acridinium compound. In conjunction with a peroxidase enhancer, continuous light emission with high light intensities and an extended duration are produced. Alternately, an appropriately designed acridan substrate produces a stable acridinium ester intermediate which can be accumulated and the chemiluminescence elicited as a burst of light by raising the pH. The effects of leaving groups and substitution on the acridan ring on the mechanism of light production are discussed. Peroxidase-catalyzed oxidation in the presence of a peroxide permits the detection of enzyme with subattomolar sensitivity and a broad linear dynamic range.

Controlled epimerization of indolo[2,3- a]quinolizidine derivatives: An efficient total synthesis of (±)-tacamonine

Base-catalysed epimerization of the easily accessible trans ester 3 at C-1 gives rise in good yield to the seemingly less stable cis ester 2, which can be converted into the indole alkaloid tacamonine ( 1) in three steps.

Design of [R-(Z)]-(+)-alpha-(methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitri le (SB 202026), a functionally selective azabicyclic muscarinic M1 agonist incorporating the N-methoxy imidoyl nitrile group as a novel ester bioisostere.

Loss of cholinergic function is believed to be implicated in the cognitive decline associated with senile dementia of the Alzheimer type (SDAT). The disease is characterized by progressive loss of muscarinic receptors located on nerve terminals while postsynaptic muscarinic M1 receptors appear to remain largely intact. Muscarinic agonists acting directly on postsynaptic receptors offer the prospect of countering the cholinergic deficit in SDAT. This study describes a novel series of azabicyclic muscarinic agonists, which incorporate an oxime ether or modified oxime ether group as an ester bioisostere. Modification of the oxime ether function by the introduction of electron withdrawing groups led to the finding that the (Z)-N-methoxy imidoyl nitrile group serves as a stable methyl ester bioisostere. This culminated in the discovery of the quinuclidinyl N-methoxy imidoyl nitrile R-(+)-(Z)-5g which is a functionally selective muscarinic M1 partial agonist currently in phase III clinical trials for the treatment of SDAT. The selective profile of R-(+)-(Z)-5g can be rationalized in terms of the relative affinity of the compound at muscarinic receptor subtypes, the degree of agonist efficacy, and brain penetrancy.

Syntheses and Biological Evaluation of 5′-O-Myristoyl Derivatives of Thymidine against Human Immunodeficiency Virus

A series of 5′- Oacyl derivatives of thymidine (dThd) were prepared by direct acylation of thymidine using the Mitsunobu reaction. Further reaction of the bromo analogues with sodium azide gave azido ester analogues. Anti-human immunodeficiency virus type 1 (HIV-1) activities were determined against HIV-infected T4 lymphocytes. 5′- O-(12-Azidododecanoyl)thymidine exhibited moderate activity (EC504.6 μM) against HIV-infected T4 lymphocytes. 5- O-(2-Bromotetradecanoyl)-thymidine was found to be the most stable ester (t1/215.3 min) to hydrolysis by porcine liver esterase in vitro. Partition coefficients (P) in n-octanol-phosphate buffer were determined (log10P range 4.15–6.72) and compared with the theoretical values calculated (log10P 3.96–6.53) using the PALLAS program. Anti-HIV structure-activity data suggest that the experimental partition coefficient should be in the log10P 4.6–4.8 range for optimum anti-HIV activity. The structures of these thymidine analogues were optimized using molecular mechanics (MM+force field) and semi-empirical quantum mechanics PM3 calculations. The moderately active compounds adopted a similar C-2′ endo sugar conformation and exhibited similar energies for the lowest energy conformer. A quantitative structure-activity relationship (QSAR) regression equation was developed, based on the optimized structures and anti-HIV data using the SciQSAR program, which showed that log P was a determinant of anti-HIV activity.

Reactions induced by triphenyl phosphite addition during melt mixing of PET/PBT blends: chromatographic evidence of a molecular weight increase due to the creation of bonds of two different natures

A detailed chromatographic investigation has been carried out on the influence of triphenyl phosphite addition in molten poly(ethylene terephthalate) or poly(ethylene terephthalate)/poly(butylene terephthalate) blends. The observed molecular weight evolution corresponds to torque and viscosity observations and fully confirms the occurrence of high temperature reactions between polyester and phosphate. The reaction mechanisms deduced from model compound studies are successfully applied to polymers. The formation of bonds of different types is verified: phosphite reactions with hydroxyl chain ends lead to the incorporation of significant quantities of phosphorus into the polyester backbone. A high sensitivity of these phosphorus containing links towards water, phenol or m-cresol has been observed. Subsequent carboxyl chain end attack on the phosphorus linkages leads to stable ester bonds.

Role of Ester Intermediates in Isobutane Alkylation and Its Consequence for the Choice of Catalyst System

Alkylation of isobutane by olefins catalyzed by Bronsted acids involves initial reaction of the olefin with the acid to form an ester intermediate. The esters formed by the reaction of olefins with triflic acid are very short-lived under typical alkylation reaction conditions but have been made by reaction of the olefin with frozen triflic acid and characterized by NMR spectroscopy. The ester intermediates are formed in an olefin-rich environment and reacts predominantly in an environment where the acid activity is high and the olefin concentration is low. This protects against oligomerization reactions, and the formation and stability of these ester intermediates in the absence of free acid, therefore, play an important role in the selectivity to the desired high-octane components typical of alkylate gasoline. The formation of relatively stable ester type intermediates represents a route to passivation of solid acid catalysts and thus favors a liquid acid catalyst for isobutane alkylation. A new fixed-bed alkylation technology using an SLP type catalyst has been developed for isobutane alkylation. It is a compromise between the wish for improved control of the acid catalyst and the chemistry of isobutane alkylation as it provides an effective control of an otherwise liquid acid catalyst without compromising the liquid phase chemistry. Results from bench-scale tests show product qualities comparable to the qualities obtained using the established technologies.

Synthesis of New d-Propoxyphene Derivatives and the Development of a Microparticle-Based Immunoassay for the Detection of Propoxyphene and Norpropoxyphene

The synthesis of [S-(R,S)]-4-[[methyl[2-methyl-3-(1-oxopropoxy)-3, 4-diphenylbutyl]amino]-1-oxobutoxy]-2,5-pyrrolidinedione+ ++ (propoxyphene active ester, 2) is described. This was used as an intermediate to prepare a propoxyphene immunogen, [S-(R,S)]-4-[methyl][2-methyl-3-(1-oxopropoxy)-3,4-diphenylbuty l]-amino]- 1-oxobutyl-Bovine Thyroglobulin (3). This immunogen was then used to generate antibodies which demonstrate good cross-reactivity to d-propoxyphene, d-norpropoxyphene, and other propoxyphene metabolites. In addition, these antibodies were shown to have very low cross-reactivity to methadone, a structurally related compound. The introduction of an aminomethyl benzoate spacer into the propoxyphene active ester (2), followed by the activation of the carboxylic acid, provided for a more stable active ester (5). This stable active ester, together with the antibodies generated from the propoxyphene immunogen, has led to the development of an immunoassay based on the Kinetic Interaction of Microparticles in Solution (KIMS).