Ester Substitution Research Articles

Organic Acids of the Microbiological Post-Culture Medium as Substrates to be Used for Starch Modification.

This study aimed to identify the feasibility of producing highly-substituted starch esters via thermal modification of starch using a post-culture medium of Yarrowia lipolitica yeast. This manuscript describes a successful attempt at potato starch modification with a post-culture medium of Yarrowia lipolitica yeast with different concentrations of organic acids. Starch preparations produced by roasting (130 °C) and these produced by starch reaction with a synthetic acid mixture were compared in terms of the types and number of acid residues esterified with starch. The effectiveness of starch esterification was found to depend on medium composition and to be higher upon the use of a synthetic acid mixture. In addition, a higher reactivity with starch was demonstrated for citric acid than for α-ketoglutaric acid. The highly-substituted starch esters formed as a result of potato starch modification with post-culture medium were characterized by decreased values of thermal parameters of pasting characteristics, determined with a differential scanning calorimeter (DSC), and by compromised resistance to amylolysis. The intensity of these changes increased along with an increasing total percentage of starch ester substitution.

Synthesis and evaluation of chromone derivatives as inhibitors of monoamine oxidase.

Based on reports that chromone compounds are good potency inhibitors of monoamine oxidase (MAO), the present study evaluates the effect of substitution with flexible side chains on the 3 position on MAO inhibition potency. Fifteen chromone derivatives were synthesised by reacting aromatic and aliphatic amines and alcohols with chromone 3-carboxylic acid in the presence of carbonyldiimidazole (CDI). This yielded chromane-2,4-dione and ester chromone derivatives. Generally, the esters exhibited weak MAO inhibition, while the chromane-2,4-dione derivatives showed promise as selective MAO-B inhibitors with IC50 values in the micromolar range. Compound 14b, 3-[(benzylamino)methylidene]-3,4-dihydro-2H-1-benzopyran-2,4-dione, was the most potent MAO-B inhibitor with an IC50 value of 638µM. This compound was shown to be a reversible and competitive MAO-B inhibitor with a Ki of 94µM. In conclusion, the effect of chain elongation and introduction of flexible substituents on position 3 of chromone were explored and the results showed that aminomethylidene substitution is preferable over ester substitution. Good potency MAO-B inhibitors may act as leads for the design and development of therapy for Parkinson's disease where these agents reduce the central metabolism of dopamine.

A monothiophene unit incorporating both fluoro and ester substitution enabling high-performance donor polymers for non-fullerene solar cells with 16.4% efficiency

Both fluorine and ester substituted monothiophene yielded a novel thiophene derivative FE-T. The resulting polymer donor S1 enabled single-junction non-fullerene solar cell with over 16% efficiency.

Functionalizing benzothiadiazole with non-conjugating ester groups as side chains in a donor–acceptor polymer improves solar cell performance

Side chain ester substitution on donor–acceptor based conjugated polymers used as solar harvesters in a bulk-heterojunction (BHJ) polymer solar cell (PSC) can improve harvesting properties, phase separation in the active layer and PSC performance.

Achieving high-efficiency purely organic room-temperature phosphorescence materials by boronic ester substitution of phenoxathiine.

The effect of boronic ester substitution on the room-temperature phosphorescence properties of phenoxathiine-based derivatives was thoroughly investigated. A significantly improved phosphorescence quantum efficiency of up to 20% in the crystalline state was achieved by delicate molecular manipulation for both enhanced spin-orbital coupling and compact intermolecular packing.

Navy-to-transmissive electrochromic polymer based on 3,4-propylenedioxythiophene

A novel conjugated polymer PProDOTCBDEM based on propylenedioxythiophene (ProDOT) with diethyl malonate (DEM) pendant group and a cyclobutane spacer between ProDOT and DEM was successfully synthesized through electrochemical polymerization. The polymer film exhibits reversible electrochromism switching between navy neutral state (− 0.1 V) and transmissive oxidized state (0.7 V). The symmetric double short chain ester substitution pattern was utilized to realize the navy color of the polymer film. The electrochemistry, spectroelectrochemistry and electrochromic switching properties of the polymer film were studied in detail.

Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules.

The utilization of carboxylic acid esters as electrophiles in metal-catalyzed cross-coupling reactions is increasingly popular, as environmentally friendly and readily available ester derivatives can be powerful alternatives to the commonly used organohalides. However, key challenges associated with the use of these chemicals remain to be addressed, including the stability of ester substrates and the high energy barrier associated with their oxidative addition to low-valent metal species. Due to recent developments in nickel catalysis that make it easier to perform oxidative additions, chemists have become interested in applying less reactive electrophiles as coupling counterparts in nickel-catalyzed transformations. Hence, our group and others have independently investigated various ester group substitutions and functionalizations enabled by nickel catalysis. Such methods are of great interest as they enable the exchange of ester groups, which can be used as directing groups in metal-catalyzed C-H functionalizations prior to their replacement. Here, we summarize our recent efforts toward the development of nickel-catalyzed decarbonylative cross-coupling reactions of carboxylic esters. Achievements accomplished by other groups in this area are also included. To this day, a number of new transformations have been successfully developed, including decarbonylative arylations, alkylations, cyanations, silylations, borylations, aminations, thioetherifications, stannylations, and hydrogenolysis reactions. These transformations proceed via a nickel-catalyzed decarbonylative pathway and have shown a high degree of reactivity and chemoselectivity, as well as several other unique advantages in terms of substrate availability, due to the use of esters as coupling partners. Although the mechanisms of these reactions have not yet been fully understood, chemists have already provided some important insights. For example, Yamamoto explored the stoichiometric nickel-mediated decarbonylation process of esters and proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO extrusion. Key nickel intermediates were isolated and characterized by Shi and co-workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted C(acyl)-O bond activation and functionalization. Our combined experimental and computational study of a ligand-controlled chemoselective nickel-catalyzed cross-coupling of aromatic esters with alkylboron reagents provided further insight into the reaction mechanism. We demonstrated that nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step, resulting in decarbonylative alkylations, while nickel complexes with monodentate phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the production of ketone products. Although more detailed mechanistic investigations need to be undertaken, the successful development of decarbonylative cross-coupling reactions can serve as a solid foundation for future studies. We believe that this type of decarbonylative cross-coupling reactions will be of significant value, in particularly in combination with the retrosynthetic analysis and synthesis of natural products and biologically active molecules. Thus, the presented ester substitution methods will pave the way for successful applications in the construction of complex frameworks by late-stage modification and functionalization of carboxylic acid derivatives.

Design and Evaluation of Short Self-Assembling Depsipeptides as Bioactive and Biodegradable Hydrogels.

Described herein is the design of a cell-adherent and degradable hydrogel. Our goal was to create a self-assembling, backbone ester-containing analogue of the cell adhesion motif, arginine–glycine–aspartic acid (RGD). Two depsipeptides containing Fmoc (N-(fluorenyl)-9-methoxycarbonyl), Fmoc-FR-Glc-D, and Fmoc-F-Glc-RGD (where “Glc” is glycolic acid) were designed based on the results of integrin-binding affinity and cell interaction analyses. Two candidate molecules were synthesized, and their gelation characteristics, degradation profiles, and ability to promote cell attachment were analyzed. We found that ester substitution within the RGD sequence significantly decreases the integrin-binding affinity and subsequent cell attachment, but when the ester moiety flanks the bioactive sequence, the molecule can maintain its integrin-binding function while permitting nonenzymatic hydrolytic degradation. A self-assembled Fmoc-F-Glc-RGD hydrogel showed steady, linear degradation over 60 days, and when mixed with Fmoc-diphenylalanine (Fmoc-FF) for improved mechanical stiffness, the depsipeptide gel exhibited improved cell attachment and viability. Though the currently designed depsipeptide has several inherent limitations, our results indicate the potential of depsipeptides as the basis for biologically functional and degradable self-assembling hydrogel materials.

An ester-substituted polyfluorene derivative for light-emitting electrochemical cells: bright blue emission and its application in a host–guest system

Ester substitution realized phase compatible film blends of a polymer and an ionic liquid for bright light-emitting electrochemical cells.

Solvent-Free Ring Cleavage Hydrazinolysis of Certain Biginelli Pyrimidines

Certain Biginelli pyrimidines with ester substitution in C5 were subjected to unexpected ring opening upon solvent-free reaction with hydrazine hydrate to give three products: pyrazole, arylidenehydrazines, and urea/thiourea, respectively. The nonisolable carbohydrazide intermediates are formed firstly followed by the intermolecular nucleophilic attack of terminal amino group of hydrazide function on sp2 C6 rather than the sp3 C4 to give the ring adduct which was produced as a final product.

Comparative conformational analyses and molecular dynamics studies of glycylglycine methyl ester and glycylglycine N-methylamide

Amide–ester substitution and water models significantly alter conformational and solvation properties of glycine–glycine dipeptides.

Copper-Catalyzed Substitution of α-Triflyloxy Nitriles and Esters with Silicon Nucleophiles under Inversion of the Configuration.

A copper-catalyzed nucleophilic displacement of α-triflyloxy nitriles and esters with silicon nucleophiles allows for the stereospecific generation of highly enantioenriched α-silylated carboxyl compounds. The enantioselective synthesis of α-silylated nitriles is unprecedented. The catalytic system exhibits good functional group tolerance. The stereochemical course of the substitution is shown to proceed with inversion of the configuration. The new reaction is an addition to the still limited number of methods for catalytic C(sp3)-Si cross-coupling.

Fatsia polycarpa Triterpenoids and Acetylated Derivatives Thereof Inhibit Tumor Necrosis Factor-α-Induced Inflammation

Fatsia polycarpa Hayata is an evergreen shrub endemic to Taiwan and used locally to treat several inflammatory disorders. The crude extract of F. polycarpa has been proven to exhibit an anti-inflammatory effect in vitro and in vivo; however, which constituents of the extract confer the anti-inflammatory function remains unclear. Fatsicarpain D (Fat D) and fatsicarpain F (Fat F) are oleanane-type triterpenoids and two of the feature constituents of the F polycarpa extract. Ester substitution on C-3 has been proposed to enhance the activities of triterpenoids. Thus, this study compared and characterized the anti-inflammatory activities of Fat D, Fat F, and the C-3-acetylated derivatives thereof. These compounds were toxic to RAW 264.7 cells, but not to FL83B cells. The compounds dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced expression of inducible nitric oxide synthase in FL83B cells, with the IC50 values being Fat D 8.5 μM, acetylated Fat D 10.4 μM, acetylated Fat F 10.7 μM, and Fat F 27.4 μM, respectively. Thus, acetylation of C-3 improved the activity of Fat F. Moreover, the compounds suppressed TNF-α-induced expression of nuclear factor-κB (NF-κB) p65 subunit and protein tyrosine phosphatase-1B. Furthermore, they inhibited TNF-α-mediated activation of the inhibitor kappa B kinase (IKK), and that of the mitogen-activated protein kinases (MAPKs) extracellular-signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), but promoted the activation of MAPK p38, which was found to be anti-inflammatory in certain cell types. Thus, Fat D and Fat F exhibited obvious anti-inflammatory activities in vitro and inhibited ERK, JNK, and the IKK/NF-κB pathway.

Synthesis and melt processing of cellulose esters for preparation of thermoforming materials and extended drug release tablets

Using softwood pulp as the starting material, the synthesis of regioselectively substituted mixed cellulose esters with varying degree of substitution and ratio of short/long chains was successfully completed. The structures of the cellulose esters were characterised. The impact of the structural changes and the degree of substitution of the cellulose esters on thermal properties and processability were investigated. The study shows that the sequential esterification is a promising modification route for cellulose to improve its thermal processability and mechanical properties without the use of external processing aids such as plasticisers. In particular, the hexanoate group in the C6 position on the cellulose backbone acts as an internal plasticiser and improves thermal processability and increases the strength and stiffness of the cellulose ester. The properties of sequentially esterified cellulose promote its practical use in plastics, coatings, films and drug delivery. Sequentially esterified cellulose hexanoate-acetate was used successfully in a coating formulation for the preparation of tablets and showed a stable extended release profile for three water-insoluble drugs in this context. The pH of the release medium had no notable effect on the release properties.

Comparative Evaluation and Optimization of Film Coating Formulation Variables and Delayed Release Properties of Three Enteric Polymers on Diclofenac Sodium Core Tablets

Enteric coatings present surfaces that have low permeability in the low pH environments of the stomach and release drug from the underlying core when they reach more neutral to alkaline environments of the intestinal milieu. However, the degree of ester substitution in the polymers, resulting in varied pH/dissolution behaviour, affects the rate and extent of drug release, the suitability of methods to be used and the overall cost of medication. In this study, hydroxypropyl methylcellulose phthalate (HPMCP) and two polymethacrylates, Wangit L30D-55® and Wangit L-100® were investigated for their enteric coating properties using diclofenac sodium tablets as core. Both polymers showed acid protective effect at the weight gain of 6%. Polymethacrylate based coatings showed somewhat better surface characteristics and drug release properties than HPMCP. The coating performance of the polymers was found to be better with lower and medium concentration of plasticizer to polymer ratio. The in vitro drug release profiles of the polymethacrylates showed cumulative drug release of 1.72% and 1.69% in 0.1 N HCl over 2 h of release study and 79.5% and 76.1% over 45 min in phosphate buffer pH 6.8, respectively. According to f2 test, the Wangit L30D-55® and Wangit L-100® coated tablets were similar to the two most commonly marketed products of diclofenac sodium 50 mg with f2 values of 66.66 and 70.88, respectively, for Marketed Product-1 (DilcoDenk®) and 59.9 and 58.74 for Marketed Product-2 (Remethan®). The results of the study showed that the polymethacrylates provide better tablet coating properties.Keywords: enteric coating, hydroxypropyl methylcellulose phthalate, polymethacrylates, diclofenac sodium, optimization

Iridium-Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates.

Enantioselective allylic substitution with enolates derived from aliphatic esters under mild conditions remains challenging. Herein we report iridium-catalyzed enantioselective allylation reactions of silyl ketene acetals, the silicon enolates of esters, to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety. Under relatively neutral conditions, the allylated aliphatic esters were obtained with excellent regioselectivity and enantioselectivity. These products were readily converted into primary alcohols, carboxylic acids, amides, isocyanates, and carbamates, as well as tetrahydrofuran and γ-butyrolactone derivatives, without erosion of enantiomeric purity.

Iridium‐Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates

AbstractEnantioselective allylic substitution with enolates derived from aliphatic esters under mild conditions remains challenging. Herein we report iridium‐catalyzed enantioselective allylation reactions of silyl ketene acetals, the silicon enolates of esters, to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety. Under relatively neutral conditions, the allylated aliphatic esters were obtained with excellent regioselectivity and enantioselectivity. These products were readily converted into primary alcohols, carboxylic acids, amides, isocyanates, and carbamates, as well as tetrahydrofuran and γ‐butyrolactone derivatives, without erosion of enantiomeric purity.

Conducting Polymer with Orthogonal Catechol and Disulfide Anchor Groups for the Assembly of Inorganic Nanostructures

To combine several inorganic components with organic material in a controlled special and permanent manner still remains a difficult issue. Two specifically functionalized block copolymers were synthesized separately and combined in a second step. A heterofunctional poly(ethylene glycol) (PEG) block copolymer bearing a single amino unit, a short PEG spacer, and multiple catechol functionalities was obtained via anionic ring-opening polymerization (AROP). Using the reversible addition–fragmentation chain transfer (RAFT) radical polymerization technique, a semiconducting block copolymer with carbazole side groups was obtained. The second polyacrylate block contained reactive ester groups and was polymerized onto this hole conducting block. By substitution of the reactive esters with the amino functional PEG-catechol block copolymer and cysteamine methyl disulfide, a hole conducting polymer material with two orthogonal anchor groups for the coating of CdSe QDs, and also for TiO2, was obtained. TEM images sho...

Synthesis of Activated Ester Functional Polyesters through Light‐Induced [4+4] Cycloaddition Polymerization

A combination of light‐induced [4+4] cycloaddition polymerization and activated ester substitution reaction is demonstrated as a new method to obtain novel polymeric structures. Bis‐anthracene functionalized compound involving perfluorophenyl ester moiety namely, bisanthracenyl‐PFPE, is prepared by an esterification reaction, then polymerized under UV light irradiated at 365 nm. The resulting polymer is reacted with a variety of amine compounds namely allylamine, benzylamine, furfurylamine, and propargylamine, under mild conditions. Quantitative conversions of perfluorophenyl ester groups into the respective amide groups as well as the thermal behaviors of all polymers are revealed by using various spectroscopic measurements such as Fourier transform infrared spectroscopy (FT‐IR), gel permeation chromatography, NMR, and differential scanning calorimetry. image

Novel cellulose esters derived from the levopimaric acid-maleic anhydride adduct: synthesis, characterization, and properties

Synthesis of maleated pimaric acid (MPA) cellulose esters is first reported in this work. Cellulose esterification was performed by reacting microcrystalline cellulose with monoacid chloride of MPA (MPA-Cl) in presence of pyridine as catalyst and reaction medium. The syntheses were started in a heterogeneous solid–liquid reaction medium, but as the reaction advanced, the reaction mass turned into a homogeneous solution. The effects of MPA-Cl/anhydroglucose unit molar ratio, reaction temperature, and reaction duration on the yield and degree of substitution (DS) of cellulose esters (CEs) were investigated. CEs with DS ranging from 2.6 to 2.8 were achieved at molar ratios of 5.5–6.0 after 12–16 h at 118 °C. The purified products were characterized by elemental analysis, IR and 13C-NMR spectroscopy, and thermogravimetric analysis. CEs are soluble or partially soluble in usual organic solvents, depending on DS. Transparent films were prepared using CE-cyclohexanone solutions.