Series Of Esters Research Articles

Influence of Chemical Modifications of Polyhydroxyalkanoate-Derived Fatty Acids on Their Antimicrobial Properties

Sugar esters are bioactive compounds derived from renewable resources. They consist of a sugar moiety with attached non-polar part – usually a fatty acid. These compounds find uses in cosmetic, food and pharmaceutical industries as surfactants due to their physicochemical and antimicrobial activities. In this study we have produced fatty acids for sugar ester synthesis from bacterially derived polyesters, namely polyhydroxyalkanoates (PHAs). We have developed methodology to decorate PHA monomers with a fluorinated moiety. With aid of biocatalysis a series of glucose esters was created with unmodified and modified PHA monomers. All synthesised compounds showed moderate antimicrobial activity.

Synthesis of Chiral β-Borylated Carboxylic Esters via Nickel-Catalyzed Asymmetric Hydrogenation.

The highly efficient Ni-catalyzed asymmetric hydrogenation of β-boronic ester substituted-α,β-unsaturated carboxylic esters was successfully developed using ( S, S)-Ph-BPE as the ligand. A series of chiral β-borylated carboxylic esters were obtained with high yields (94%-99% yields) and excellent enantioselectivities (89%-99% ee). The gram-scale asymmetric hydrogenation with a low catalyst loading (0.25 mol %) and synthetic transformation of hydrogenation product demonstrated the great synthetic utility of this methodology.

Kazbek – The First Czech Aroma “Flavor Hops” Variety: Characteristics and Utilization

The world market of craft beer, especially dry hopped beers, has been constantly growing in the last few years. That is why new varieties of hops are still being bred. This article gives the genetic, agronomic, chemotaxonomic and brewing characteristics of Kazbek, the first “flavor hops” variety bred in the Czech Republic. Kazbek genetically belongs to a group of bitter American hops resulting from Brewers Gold variety, but the alpha acids content is relatively low, 5.0–8.0% by weight. The content of a homologous series of geranyl esters (acetate – propionate – isobutyrate) in an amount 2–4% of total essential oils (1–1.5 g/100g) is considered to be the originator of the specific, mainly citrus-like aroma of Kazbek. Moreover, the essential oil fraction contains about 25 sulfurous substances, predominantly thioesters. In the pilot scale brewing tests, the quality of Kazbek hops was proved both in kettle and dry hopping of Pilsner lagers. The overall sensory impression of kettle hopped lagers was comparable to Saaz hops, the differences were in the character of hop-derived flavor and bitterness. The best results of dry hopped beers were achieved for a 2.5 g/l hop dose and a contact time of 3 days.

Does the Exception Prove the Rule? A Comparative Study of Supramolecular Synthons in a Series of Lactam Esters

In this paper a series of simple lactam esters and carboxylic acids is studied with respect to their overall conformation and hydrogen bonding patterns. In total, eight lactams featuring Nα-substitution have been synthesized. Additionally, the molecular structures of related lactam esters have been considered. The length of the amide bonds does not seem to be majorly influenced by different substituents unless the electron withdrawing N-Boc-protection group is introduced, resulting in a higher susceptibility toward hydrolytic ring opening. As known from other lactams, the Nα ester moiety of the title compounds can be in an axial or equatorial conformation. Smaller ester groups were found to prefer equatorial positions, while larger ones occupy axial sites. N-substitution seems to promote axial conformations of the respective Nα group, with enantholactams being the only studied exception. In addition to the two common amide packing motifs, i.e., the R22(8) amide dimer (NH···O/NH···O) and the C(4) amide chain, a third graph-set was found: the R22(8) NH···O/CH···O═C heterodimer. In general, there seems to be a tendency for medium-sized lactams as well as lactams with small esters to form R22(8) amide dimers. Larger esters and enantholactam esters lead to C(4) amide chains. In this respect the formation of R22(8) N—H···O/C–H···O═C heterodimers should be seen as a remarkable exception.

Ester appended organosilatranes: Paradigm for the detection of Cu2+, Pb2+ and Hg2+ ion

A new series of ester appended organosilatranes (5a–f) were developed for the specific and selective detection of Cu2+, Hg2+ and Pb2+ and were well characterized by various spectroscopic techniques. The newly synthesized silatranes (5a–f) were appraised for heavy metal ion binding properties using UV-vis and photoluminescent spectra. In addition the stern volmer plot confirmed the quenching phenomenon on addition of Cu2+, Hg2+ and Pb2+. Interestingly, the detection limit of 5a-f with Cu2+, 5b with Hg2+ and 5d with Pb2+ is 1.07–3.56 µM, 1.43 and 1.65 respectively. In a nutshell, the present article provides the cost-effective and promising platform for detection of these ions.

2-D Self-assembly of Alkyl-substituted Oligophenylene Derivatives at the Liquid/Solid Interface: Influence of Core Size and Hydrogen Bonds on the Nucleation–Elongation Process

The adsorption process at a liquid/graphite interface was investigated by scanning tunneling microscopy for a series of ester and amide derivatives which have a different number of phenyl rings in ...

A preliminary study on quinazolinylaminobenzoyl monopeptide esters as effective Gram-positive bacteriostatic agents.

To investigate a novel series of quinazoline monopeptide esters for the in vitro antibacterial activity. The compounds were synthesized via one-pot Dimroth rearrangement of suitable formamidine intermediates with 3-aminobenzoic acid, followed by coupling the resulting acids with amino acid esters and screening for their antibacterial activity by broth dilution method. The compounds 5a, 5b, 5c, 5g, 5i and 5j showed promising activity against the Gram-positive bacteria, 5c and 5g being the most potent against Enterococcus faecalis and Staphylococcus aureus, respectively, with a minimal inhibitory concentration of 0.51μM. The percentage hemolysis of the compounds ranged from 2.79 to 12.92 at a concentration of 100μg/ml. The molecular docking studies revealed their GlmU inhibitory action. The compounds 5a and 5g emerged as antibacterial hits.

Hidden Specificities in Enzyme Catalysis: Structural Basis of Substrate Structure-Selectivity Relationship of a Ketoreductase.

Enzymes often convert both physiological and non-physiological substrates with high stereoselectivity; yet, for some enzymes, opposite product chirality is observed. A possible explanation is the existence of hidden specificities becoming apparent when non-physiological substrates confer different substrate-enzyme interactions than the physiological substrate. To test this hypothesis, a series of α-methylated β-keto esters were converted with Tyl-KR1, a ketoreductase from polyketide synthesis in Streptomyces fradiae. The conversions of six substrates with different physicochemical properties exhibited enantioselectivities ranging from 84 % ee for R,R to 84 % ee for S,S, yet high and uniform diastereoselectivity (anti, d.r.>9:1). The exchange of a single atom, namely an oxygen ester instead of a thioester, led to almost complete loss of enantioselectivity (<5 % ee). An additional S,S-selective binding mode as a hidden specificity in Tyl-KR1 has been identified through molecular modeling and site-directed mutagenesis.

Control of Excited-State Supramolecular Assembly Leading to Halide Photorelease.

Ground- and excited-state control of halide supramolecular assembly was achieved through the preparation of a series of ester- and amide-functionalized ruthenium polypyridyl complexes in CH2Cl2. Hydrogen-bonding amide and alcohol groups on the receptor ligand were found to direct interactions with halide, while halide association with the ethyl ester groups was not observed. The various functional groups on the receptor ligands tuned the ground-state equilibrium constants over 2 orders of magnitude (1 × 105 to 1 × 107 M-1), and the fractional contribution of each hydrogen-bond donor to the total equilibrium constant was determined. Pulsed-laser excitation of the complexes resulted in excited-state localization on the ester- or amide-functionalized ligands. In the case where the excited state was oriented toward an associated halide ion (the amide complexes), an 80 ± 10 meV Coulombic repulsion was induced that lowered the excited-state equilibrium constant ( K*eq) and resulted in halide photorelease. The rate constants for excited-state halide release ( k*21) were determined, and the values varied based on the functional groups present in the receptor ligand. Complexes with more hydrogen-bonding donors had smaller rate constants for halide photorelease. In a complex without a specific receptor ligand, the excited-state dipole was not oriented toward the associated halide, and the excited state was therefore found to have a larger equilibrium constant for halide association than the ground state.

Proline derivatives incorporating hydrophobic long-chain derived from natural and synthetic fatty acids

The α-hydrophobic long chain-α-amino esters are prepared by α-hydroxylation of a series of fatty acid esters [derived from oleic acid (OA), linoleic acid (LA), arachidonic acid (ARA) and docosahexaenoic acid (DHA)] followed by Mitsunobu reaction and hydrazinolysis of the phthalimide. These amino esters are mixed with aldehydes and electrophilic alkenes to give very good chemical yields and diastereoselectivities of prolinate derivatives incorporating a hydrophobic long chain at the α-position. This multicomponent 1,3-dipolar cycloaddition (1,3-DC) takes place at room temperature. The synthesis of the homologue hydrophobic chain of OA is performed by its oxidation to aldehyde/racemic N-tert-butylsulfinyl imine/Neff reaction. Final 1,3-DC with benzaldehyde and N-methylmaleimide affords homologue prolinate derivative in good yield.

Synthesis and application of novel magnesium phosphate ester flame retardants for transparent intumescent fire-retardant coatings applied on wood substrates

A series of magnesium phosphate ester (MPEA) flame retardants were synthesized by the salification of cyclic phosphate ester (PEA) with different contents of magnesium hydroxide (MH). The obtained PEA and MPEAs were well characterized and then thoroughly mixed with amino resin to produce transparent intumescent fire-retardant coatings applied on wood substrates. The optical transparency, flame retardancy and smoke suppression properties of the coatings were intensively investigated. The results show that the fire-retardant coatings containing MPEAs can keep a high degree of transparency even at high MH contents, and the fire protection performance, flame retardancy and smoke suppression properties of the coatings are significantly improved with introduction of MH due to the formation of a more compact, continuous and intumescent char during combustion. When the mass ratio of PEA/MH is 95:5, the obtained MPEA3 flame retardant exhibits the best synergistic flame-retardant and smoke suppression effects in the coatings. Remarkably, the flame spread rating, total heat release and total smoke release for the coating containing MPEA3 are 34.4%, 29.0% and 55.0% lower, respectively, than those of the coating containing PEA. TG analysis shows that the introduction of MH improves the thermal stability and residual weight of the coatings, and the coating containing MPEA3 shows the maximum residual weight of 34.4% at 800 °C. Char residue analysis shows that the introduction of MH positively contributes to enhance the quality and quantity of intumescent char via the formation of more phosphorus-rich crosslinking structures and aromatic structures in the condensed phase, and an excessive content of MH diminishes this positive char-forming effect as well as the synergistic flame-retardant and smoke suppression effects in the coatings.

Development of piperic acid-based monoamine oxidase inhibitors: Synthesis, structural characterization and biological evaluation

A series of piperic acid esters and amides were synthesized using a two-step strategy. Mass spectrometry and unidimensional (1H NMR, 13C NMR, DEPT) and bidimensional (COSY, HSQC, HMBC) NMR methodologies were used to study the molecular structure of the final compounds, resulting in the assignment of all detected signals.Preliminary biological data of piperine and the derivatives thereof showed that piperic acid 2 and amides 3 and 4 did not display significant inhibitory activity at 10 μM against both hMAO-A and hMAO-B. In contrast, the esters 5 and 6 displayed relevant hMAO inhibitory activities, with IC50 values for hMAO-B lower than piperine and within the nanomolar range (compound 1: IC50 = 1.05 μM; compound 6: IC50 = 169 nM; compound 5: IC50 = 156 nM). Moreover, X-ray crystallographic analyses showed relevant differences between amides 3 and 4 and esters 5 and 6 constituting a valuable information to understand the ligand-target interactions.Additional studies are warranted for a systematic lead optimization process that can lead in the future to a more potent and selective hMAO-B inhibitor based on piperine scaffold.

Direct Transformation from Arylamines to Aryl Naphthalene-1,8-diamino Boronamides: A Metal-Free Sandmeyer-Type Process.

A direct metal-free transformation from arylamines to aryl naphthalene-1,8-diamino boronamides, a type of masked boronic acid, has been developed based on Sandmeyer-type reactions. A nonsymmetrical diboron reagent, B(pin)-B(dan), was utilized as the borylating reagent, and the B(dan) moiety was transferred to the aim products selectively. This conversion tolerated a series of functional groups, including chloro, bromo, fluoro, ester, hydroxy, cyano and amide.

Development of novel apoferritin formulations for antitumour benzothiazoles.

BackgroundThe benzothiazole structure is important in medicinal chemistry, and 5‐fluoro‐2‐(3,4‐dimethoxyphenyl) benzothiazole (GW 610) is of particular interest as it shows outstanding anticancer activity in sensitive breast and colorectal carcinoma cell lines via generation of lethal DNA adducts in sensitive cancer cells. Despite promising activity, poor water solubility limits its applications. The apoferritin (AFt) protein cage has been proposed as a robust and biocompatible drug delivery vehicle.AimsHere, we aim to enhance solubility of GW 610 by developing amino acid prodrug conjugates and utilizing the AFt capsule as drug delivery vessel.Methods and resultsThe potent experimental antitumour agent, GW 610, has been successfully encapsulated within AFt with more than 190 molecules per AFt cage. The AFt‐GW 610 complex exhibits dose‐dependent growth inhibition and is more potent than GW 610 alone in 5/7 cancer cell lines. To enhance both aqueous solubility and encapsulation efficiency, a series of amino acid esters of GW 608 prodrug were synthesized via N,N′‐dicyclohexylcarbodiimide ester coupling to produce molecules with different polarity. A dramatic increase in encapsulation efficiency was achieved, with more than 380 molecules of GW 608‐Lys molecules per AFt cage. Release studies show sustained release of the cargo over 12 hours at physiologically relevant pH. The AFt‐encapsulated amino acid modified GW 608 complexes are sequestered more rapidly and exhibit more potent anticancer activity than unencapsulated agent.ConclusionThese results indicate that AFt‐encapsulation of GW 610 prodrug provides a biocompatible delivery option for this potent, selective experimental antitumour agent and for amino acid‐modified GW 608. Of particular interest is the encapsulation efficiency and in vitro antitumour activity of AFt‐GW 608‐Lys, which warrants further preclinical evaluation.

Synthesis and anticancer activity of chalcone analogues with sulfonyl groups

Three series of sulfonyl esters were synthesized in reactions of sulfonyl chlorides with three different phenolic chalcone analogues (dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one), (E)-1-(4-hydroxy-3-methoxyphenyl)pent-1-en-3-one, and (E)-1-(4-hydroxy-3-methoxyphenyl)-5-methylhex-1-en-3-one). The structures of the new compounds were determined by IR, MS, and NMR methods. Screening of the new sulfonyl esters’ in vitro cytotoxic activities against human epithelial cervical carcinoma (HeLa) and normal human fibroblast (MRC-5) cell lines by the MTT method was performed. The five most active were selected and further tested on HeLa, MRC-5, and MCF-7 (breast carcinoma) cell lines. The examined compounds exhibit strong in vitro anticancer activities with moderate-to-high selectivity, inducing apoptotic cell death and cell cycle arrest in both HeLa and MCF-7 cell lines, but have little to no effect on the non-cancerous MRC-5 cell line.

Highly ordered columnar superlattice nanostructures with improved charge carrier mobility by thermotropic self-assembly of triphenylene-based discotics

A series of triphenylene esters with two ester groups at different substituent positions was synthesized and investigated. 3,6-substituted molecule formed a helical hexagonal columnar superstructure, leading to improved charge carrier mobility.

Phosphorus Flame Retardants for Polymeric Materials from Gallic Acid and Other Naturally Occurring Multihydroxybenzoic Acids

The development of polymer and polymer additives from renewable biosources is becoming increasingly prominent. This reflects increasing concerns about sustainability, environmental quality, and human health. Bioproducts produced in nature are generally inexpensive and benign in the environment. Moreover, degradation of derivatives does not yield toxic products. Gallic acid (3,4,5-trihydroxybenzoic acid) is found widely in nature and has long been touted for its medicinal qualities. 3,5-Dihydroxybenzoic acid is also produced by several plants, most notably buckwheat. Both compounds, as the anilide and methyl ester, respectively, have been converted to a series of phosphorus esters, both phosphonate and phosphate. Esters have been fully characterized using spectroscopic and thermal methods. These compounds display good flame retardancy at low loadings in DGEBA epoxy resin.

Synthesis and characterization of five diiron ethanedithiolate complexes with acetate group and phosphine ligands

A series of acetate ester containing diiron ethanedithiolate complexes have been synthesized and structurally characterized. CO substitution of complex [Fe2(CO)6{μ-SCH2CH(CH2O2CCH3)S}] (1) with the phosphine ligands tris(2-furyl)phosphine, tris(2-thienyl)phosphine, tris(4-fluorophenyl)phosphine, tris(4-chlorophenyl)phosphine, or cyclohexyldiphenylphosphine in the presence of the decarbonylating agent Me3NO·2H2O gave the phosphine-substituted diiron derivatives [Fe2(CO)5(L){μ-SCH2CH(CH2O2CCH3)S}] (L = P(2-C4H3O)3, 2; P(2-C4H3S)3, 3; P(4-C6H4F)3, 4; P(4-C6H4Cl)3, 5; Ph2PC6H11, 6) in 86–95% yields. The complexes 2–6 have been characterized by elemental analysis, spectroscopy, and X-ray diffraction analysis. Additionally, the electrochemical properties were investigated by cyclic voltammetry.

Synthesis of eugenol derivatives and its anti-inflammatory activity against skin inflammation

Eugenol is a phytochemical present in aromatic plants has generated considerable interest in the pharmaceutical industries mainly in cosmetics. A series of eugenol esters (ST1-ST7) and chloro eugenol (ST8) have been synthesized. The structures of newly synthesized compounds were confirmed by 1H and 13C NMR and mass spectrometry. In an effort to evaluate the pharmacological activity of eugenol derivatives, we explored its anti-inflammatory potential against skin inflammation using in-vitro and in-vivo bioassay. Synthesized derivatives significantly inhibited the production of pro-inflammatory cytokines against LPS-induced inflammation in macrophages. Among all derivatives, ST8 [Chloroeugenol (6-chloro, 2-methoxy-4-(prop-2-en-1-yl)-phenol)] exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the efficacy and safety in in-vivo condition. ST8 exhibited significant anti-inflammatory activity against TPA-induced skin inflammation without any skin irritation effect on experimental animals. These findings suggested that ST8 may be a useful therapeutic candidate for the treatment of skin inflammation.

Biobased Plasticizers from Carbohydrate-Derived 2,5-Bis(hydroxymethyl)furan

As potential replacements for phthalate plasticizers, a series of esters of biobased 2,5-bis(hydroxymethyl)furan has been synthesized and fully characterized using spectroscopic and thermal methods...