Hydrolysis Of Ethyl Research Articles

Biocatalytic hydrolysis of various esters using Baker’s yeast under neutral conditions without sucrose

We have found that biocatalytic hydrolysis of various esters using Baker’s yeast proceeds efficiently under neutral conditions without sucrose. Hydrolysis of ethyl, methyl, propyl, isopropyl, benzyl, allyl, prenyl, and vinyl esters of 3-phenylpropanoic acid using Baker’s yeast gave easily 3-phenylpropanoic acid in 52–86% yields. In contrast, Baker’s yeast did not hydrolyze the rigid structural esters such as cinnamyl and phenyl 3-phenylpropanoates. Then, Baker’s yeast hydrolyzed various ethyl esters of 3-arylpropanoic acids, 4-phenylbutanoic acid, and fatty acids to afford the corresponding acids in 29–85% yields.

Development and Validation of an HPLC Method for the Determination of p-methoxycinnamic Acid in Rabbit Plasma

p-methoxycinnamic acid (pMCA) is an active compound obtained from the hydrolysis of ethyl p- methoxycinnamate acid (EpMC). It is isolated from Kaempferia galanga Linn with anti-inflammatory and analgesic effects. A simple, rapid, accurate and selective high performance liquid chromatography method was developed to determine the p-methoxycinnamic acid consentrations in rabbit plasma using a C18 reversed-phase analytical column. Ethanol was used for protein precipitation to prepare plasma samples, with chromatographic separation performed using a µ-Bondapak C18 (3.9 mm x 300 mm i.d). The mobile phase consists of methanol and water (30:70), with a flow rate 0.8 mL/min, maximum pressure of 300 bars and UV detection of 286 nm. The proposed method was validated by performing selectivity, linearity, accuracy, precision, LOD and LOQ for pMCA with no interfering peaks. Its overall analytical run time was 10 min, which is useful for in vivo studies of p-methoxycinnamic acid.

TRANSFORMATION OF ETHYL-P-METHOXYCINNAMATE TO P –METHOXYCINNAMIC ACID FROM KENCUR (Kaempheria galanga L.) AND THEIR ANTIBACTERIAL ACTIVITY

This study aimed to evaluate the antibacterial properties of ethyl-<em>p</em>-methoxycinnamate and <em>p</em>-methoxycinnamate acid from Kaempheria galanga L. Ethyl-<em>p</em>-methoxycinnamate was isolated from the <em>n</em>-hexane rhizome extract of <em>Kaempheria galanga L</em>. Separation and purification of this compound was carried out with vacuum liquid chromatography and column chromatography. Hydrolysis of ethyl-<em>p</em>-methoxycinnamic under alkaline conditions obtained <em>p</em>-methoxycinnamic acid with a good yield of 85 %. The structure of the compounds were charactrized with IR, NMR spectrophotometer (<sup>1</sup>H-NMR and <sup>13</sup>C-NMR) and mass spectrophotometer. The antibacterial properties of the compounds were evaluated using microdilution methods against <em>B. cereus</em> ATCC 11778, <em>L. monocytogenes</em> ATCC 7644, <em>E. coli</em> ATCC 25922, <em>S. enterica sv Typhimurium</em> ATCC 14028, and <em>E. aerogenes</em> ATCC 13048. The compounds showed weak antibacterial properties. Only ethyl <em>p</em>-methoxycinnamate showed the strongest antibacterial activity, especially against <em>B. cereus</em> ATCC 11778 bacteria with MIC values of 62.5 mg /mL. The change of the functional groups provided no significant impact on the antibacterial activity.

Synthesis of ethyl ({[adamantan-1(2)-ylalkyl]-carbamothioyl}amino)acetates

Reactions of adamantan-1(2)-amines and adamantan-1(2)-ylalkanamines with ethyl isothiocyanatoacetate afforded ethyl ({[adamantan-1(2)-ylalkyl]carbamothioyl}amino)acetates in 85–95% yields. The hydrolysis of ethyl {[(adamantan-2-yl)carbamothioyl]amino}acetate in alkaline medium resulted in the formation of {[(adamantan-2-yl)carbamothioyl]amino}acetic acid in a virtually quantitative yield.

Synthesis of new 1-(3,4-dimethylphenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one derivatives

New substituted pyrazolo[3,4-d]pyrimidin-4-ones have been synthesized as a result of a series of transformations including hydrolysis of ethyl 5-amino-1H-pyrazole-4-carboxylates, cyclization of the carboxylic acids thus obtained to pyrazolo[3,4-d][1,3]oxazin-4(1H)-ones, and treatment of the latter with substituted anilines. The final pyrazolo[3,4-d]pyrimidin-4-one derivatives can also be synthesized from 5-(arylamido)-1H-pyrazole-4-carboxylic acids in the presence of a catalytic amount of anhydrous zinc(II) chloride.

Enzymatic Synthesis of a Key Intermediate for Rosuvastatin by Nitrilase‐Catalyzed Hydrolysis of Ethyl (R)‐4‐Cyano‐3‐hydroxybutyate at High Substrate Concentration

AbstractAn enzymatic method for the synthesis of ethyl (R)‐3‐hydroxyglutarate from ethyl (R)‐4‐cyano‐3‐hydroxybutyate was developed by using free and immobilized recombinant Escherichia coli BL21(DE3)pLysS harboring a nitrilase gene from Arabidopsis thaliana (AtNIT2). The hydrolysis of ethyl (R)‐4‐cyano‐3‐hydroxybutyate proceeded with the freely suspended cells of the biocatalyst under the optimized conditions of 1.5 mol L−1 (235.5 g L−1) substrate concentration and 6.0 wt % loading of wet cells at pH 8.0 and 25 °C, with 100 % conversion obtained in 4.5 h. Furthermore, immobilization of the whole cells enhanced their substrate tolerance, stability, and reusability. Under the optimized conditions (100 mmol L−1 tris(hydroxymethyl)aminomethane hydrochloride buffer, pH 8.0, 25 °C), the immobilized biocatalyst could be reused for up to 16 batches, with a biocatalyst productivity of 55.6 g gwet cells−1 and a space‐time productivity of 625.5 g L−1 d−1. These results demonstrated that the immobilized whole cells might be used as a biocatalyst in the industrial production of ethyl (R)‐3‐hydroxyglutarate, a key intermediate for the synthesis of rosuvastatin.

Synthesis and anticancer activity of some new pyrazolo[3,4-d]pyrimidin-4-one derivatives.

3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d][1,3]oxazin-4-one (3) was prepared by hydrolysis of ethyl 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (1) to afford the corresponding carboxylic acid 2, which was reacted with acetic anhydride to give 3. The pyrazolo[3,4-d][1,3]oxazin-4-one 3 was reacted with hydroxylamine hydrochloride, urea, thiourea, thiosemicarbazide, phenylhydrazine and aromatic amines to afford the corresponding pyrazolo[3,4-d]pyrimidin-4-ones 4, 5a,b, 6, 7, 8a–e, respectively. Condensation of pyrazoloxazine derivative 3 with 99% hydrazine hydrate afforded the 5-aminopyrazolo[3,4-d]pyrimidine derivative 9. Coupling of 9 with aromatic aldehydes yielded a series of 3,6-dimethyl-5-(4-substitutedbenzylideneamino)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-ones 10a–e. The new compounds were tested for their antitumor activity on the MCF-7 human breast adenocarcinoma cell line. Almost all the tested compounds revealed antitumor activity, especially 3,6-dimethyl-5-(4-nitrobenzylideneamino)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one (10e) which displayed the most potent inhibitory activity with a half maximal inhibitory concentration (IC50) of 11 µM.

Improved synthesis of 4-phenylphenalenones: the case of isoanigorufone and structural analogs

2-Hydroxy-4-phenyl-1H-phenalen-1-one (isoanigorufone, 1), a phytoalexin exclusive of Musaceae, was synthesized starting from 3-(2-hydroxynaphthalen-1-yl)propanenitrile in nine steps in an overall yield of 10%. Hydrolysis of ethyl 3-(2-phenylnaphthalen-1-yl)propanoate obtained from Suzuki–Miyaura coupling between the parent triflate and phenylboronic acid afforded the corresponding propionic acid which, after Friedel–Crafts acylation and bromine-mediated dehydrogenation, was subjected to Yang–Finnegan epoxidation to furnish 1. The preparation of analogs using this procedure is also discussed.

Highly Enantioselective Sequential Hydrogenation of Ethyl 2-Oxo-4-arylbut-3-enoate to Ethyl 2-Hydroxy-4-arylbutyrate

The hydrogenation of (E)-ethyl 2-oxo-4-arylbut-3-enoate with [NH2Me2](+)[{RuCl [(S)-SunPhos]}2(mu-Cl3)] gave ethyl 2-hydroxy-4-arylbutyrate with 94-96% ee. Further investigation has proved that the hydrogenation proceeded via a sequential hydrogenation of CO and CC bonds, which is sensitive to the reaction temperature. Hydrolysis of ethyl 2-hydroxy-4-phenylbutyrate (ee 93%) provided the 2-hydroxy-4-phenylbutyric acid with 81% yield at 99% ee after a single recrystallization from 1,2-dichloroethylene.

Solvent-free Friedel-Crafts Reaction for Regioselective Synthesis of Ethyl (9-Anthryl)glyoxylate and Chiral Resolution of (±)-(9-Anthryl)hydroxyacetic Acid

A green chemistry-based highly regioselective synthesis of ethyl (9-anthryl)glyoxylate was achieved by solvent-free Friedel-Crafts reaction at r. t. Several derivatives of ethyl (9-anthryl)glyoxylate were also synthesized. Ethyl (9-anthryl)hydroxyacetate was obtained almost quantitatively by reduction of ethyl (9-anthryl)glyoxylate with NaBH4, and (9-anthryl)methoxyacetic acid was prepared by methylation of ethyl (9-anthryl)hydroxyacetate with CH3I in the presence of Ag2O and hydrolysis of ethyl (9-anthryl)methoxyacetate. The hydrolysis of ethyl (9-anthryl)hydroxyacetate gave racemic (9-anthryl)hydroxyacetic acid, and the racemate was successfully resolved by crystallization of the diastereomeric salts resulting from the reaction of (±)-(9-anthryl)hydroxyacetic acid with (-)-ephedrine. As a byproduct, crystals containing racemic (±)-(9-anthryl)hydroxyacetate and protonated (-)-ephedrine were isolated and their structures determined by X-ray diffraction.

Novel Convenient Synthesis of Mitiglinide

A novel convenient synthesis of the hypoglycemic agent mitiglinide was developed. (2S)‐4‐[(3aR,7aS)‐Octahydro‐2H‐isoindol‐2‐yl]‐4‐oxo‐2‐benzyl‐butanoic acid (6) was prepared by selective hydrolysis of ethyl 4‐[(3aR,7aS)‐octahydro‐2H‐isoindol‐2‐yl]‐4‐oxo‐2‐benzyl‐butanoate (5) using α‐chymotrypsin; the latter was prepared by a novel facile route from (3aR,7aS)‐octahydro‐2H‐isoindole. The overall yield was 25.6%.

Simple and effective method for the deracemization of ethyl 1-hydroxyphosphinate using biocatalysts with lipolytic activity

The kinetic resolution of ethyl (1-hydroxyethyl)phenylphosphinate was carried by enzymatic esterification with vinyl butyrate or by hydrolysis of ethyl (1-butyryloxyethyl)phenylphosphinate either by the use of lipases or whole cells of microorganisms (bacteria and fungi). Since no stereodifferentiation of the phosphinate moiety was observed, the biotransformations gave diastereoisomers of ethyl (1-hydroxyethyl)phenylphosphinate with excellent enantiomeric excesses above 98%, while the percentage conversion ranged from 10% to 49% depending upon the procedure and conditions of the biocatalysis.

Synthesis of Fluorine‐Containing 2‐(1‐Aryl‐4‐oxo‐1,4‐dihydrocinnolin‐3‐yl)‐2‐oxoacetic Acids.

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1-Methyl-4-nitro-1H-imidazole-2-carboxylic acid dihydrate

The hydrolysis of ethyl 1-methyl-4-nitro-1H-imidazole-2-carboxyl­ate leads to 1-methyl-4-nitro-1H-imidazol-2-carboxylic acid, which crystallizes as a dihydrate, C5H5N3O4·2H2O. The planar organic entity is a flat mol­ecule; the mol­ecules are linked through the water mol­ecules by hydrogen bonding into a three-dimensional network.

Synthesis and Reactions of Some New Heterocyclic Compounds Containing Cycloalka[e]thieno[2,3-b]pyridine Moiety

Hydrolysis of ethyl 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxylates (3a-d) gave the corresponding o-aminocarboxylic acids 4a-d. Heating the latter compounds (4a-d) with acetic anhydride furnished the oxazinone derivatives 5a-d which, in turn, underwent recyclization reaction to give the corresponding pyrimidinones 6a-d upon treatment with ammonium acetate in acetic acid. Reaction of 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides (3f,h) with triethyl orthoformate gave pyrimidinone derivatives 7a,b. Reaction of 3-amino-4-phenyl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides 3e,h with aromatic aldehydes furnished tetrahydropyridothienopyrimidinones 8a-d. Chlorination of 7a,b and 6a-d by using phosphorous oxychloride produced 4-chlorocycloalka[5′,6′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivatives 9a-f which were used as key intermediates in the synthesis of several new cycloalkapyrido-thienopyrimidines 10a-f˜14a-f. Moreover, some cycloalkapyridothienotriazinones 15a,b-17a,b were synthesized.

Synthesis of Fluorine-Containing 2-(1-Aryl-4-oxo-1,4-dihydrocinnolin-3-yl)-2-oxoacetic Acids

Acid hydrolysis of ethyl 2-(1-aryl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydrocinnolin-3-yl)-2-oxoacetates gives 2-(1-aryl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydrocinnolin-3-yl)-2,2-dihydroxyacetic acids which undergo dehydration on heating in toluene to afford 2-(1-aryl-5,6,7,8-tetrafluoro-4-oxo-1,4-dihydrocinnolin-3-yl)-2-oxoacetic acids. Reactions of the latter with excess morpholine result in replacement of two fluorine atoms in positions 5 and 7 by the amine residues.

Hydrolysis of N‐aryl thioncarbamate esters. Modified Marcus equation for reactions with asymmetric intrinsic barriers

AbstractThe hydrolysis of ethyl N‐p‐substituted arylthioncarbamates was studied at 100 °C in the pH range 6.5–12.5. No general catalysis was found, and the presence of an isothiocyanate intermediate was detected, indicating that the alkaline hydrolysis occurs by an E1cb mechanism. From the pH–rate profiles, the first‐order rate constants kE for the elimination step of the thioncarbamate anion forming the isothiocyanate intermediate were determined. The alkaline hydrolysis of p‐substituted arylisothiocyanates was studied at 25 °C in 0.1–0.3 M solutions of NaOH and in 0.1–0.3 M aqueous ethanol solutions, at different concentrations of NaOH. The second‐order rate constants for the addition reaction with hydroxide (kOH) and ethoxide (kA) ions were obtained. Leffler plots for the elimination of the ethoxide ion from the arylthioncarbamate anion and for the addition of the ethoxide ion to the arylisothiocyanate were linear. From Leffler's equation, with the sole condition that dαL/dΔG should be constant, a modified Marcus equation (MME) was obtained, where a parameter p (or q for the reverse reaction) defined the asymmetry of the intrinsic barrier. (When p = 1/2 the barrier is symmetric and the MME becomes the Marcus equation in the usual form.) For the addition–elimination reaction studied, both Leffler plots were adjusted to MME with the asymmetric parameter p = 0.694 ± 0.002 for the addition and q = 0.307 ± 0.002 for the elimination reaction. The intrinsic barrier was $\Delta G_{0}^{\neq} = 24.75 \pm 0.02\,\hbox{kcal mol}^{-1}$ and |ΔGmax| = 438 ± 4 kcal mol−1 (1 kcal = 4.184 kJ). The addition reaction was exoergic and, as expected from the high intrinsic barrier, αL changed very little in the series (0.679–0.683); the transition state was product‐like, and it moved towards the reagents with increasing exoergicity. Copyright © 2002 John Wiley & Sons, Ltd.

Antioxidative or prooxidative effect of 4-hydroxyquinoline derivatives on free-radical-initiated hemolysis of erythrocytes is due to its distributive status

7-Chloro-4-hydroxyquinoline (CQ) is an antitumor drug but its efficiency is not very satisfactory. This fact motivates us to study the relationship between the structure of 4-hydroxyquinoline with various substituent and its antioxidant effect against free-radical-initiated peroxidation: the hemolysis of human erythrocyte initiated thermally by water-soluble initiator, 2,2′-azobis (2-amidinopropane hydrochloride) (AAPH), acts as an experimental system. 7-Fluoro-4-hydroxyquinoline (FQ) and CQ can be synthesized by decarboxylation of 7-fluoro-4-hydroxyquinoline-3-carboxylic acid (FQCA) and 7-chloro-4-hydroxyquinoline-3-carboxylic acid (CQCA), respectively, and FQCA and CQCA are prepared by hydrolysis of ethyl 7-fluoro-4-hydroxyquinoline-3-carboxylate (FQCE) and ethyl 7-chloro-4-hydroxyquinoline-3-carboxylate (CQCE), respectively. The inhibitory concentration of 50% inhibition (IC 50) of AAPH-induced hemolysis of the erythrocyte has been studied and found that all these chemicals dissolved in dimethyl sulfoxide (DMSO) can inhibit the free-radical-induced peroxidation. To clarify the relationship between the distributive status of the chemicals and their antioxidant effect, the chemical has been dissolved in the vesicle of dipalmitoyl phosphatidylcholine (DPPC) by sonication and suspended in the reaction system. It is found that FQCE, CQCE, FQCA and CQCA act as prooxidants either used alone or used in combination with α-tocopherol (TOH), demonstrating that FQCE, CQCE, FQCA and CQCA play a prooxidative role when they are packaged in the DPPC vesicle. This can be understood that the electron-attracting group, i.e. -COOC 2H 5, -COOH, at the ortho position to the hydroxy group of quinoline makes the phenoxy radical of quinoline derivatives active by attracting negative charge from the electron-deficient radical site. These unstable free radicals preserved in DPPC vesicle can initiate additional propagation of lipid peroxidation and cause hemolysis. However, FQ and CQ without electron-attracting group are antioxidants even in DPPC vesicle either used alone, or mixed with TOH. Moreover, the antioxidative activity of FQ is much better than CQ either used alone or in combination with TOH, indicating that FQ has the potential to replace CQ to be an antioxidant drug. Therefore, the antioxidant/prooxidant effect is not only correlated with the molecular structure but also the distributive status in the reaction system.

Enantioselectivity Related to Conformational Changes Observed by Spectral Analysis in Subtilisin-Catalyzed Hydrolysis of Ethyl (RS)-2-(4-Substituted Phenoxy)Propionates

The enantioselectivity for the subtilisin-catalyzed hydrolysis of ethyl (RS)-2-(4-substituted phenoxy)propionates in aqueous buffer was found to be improved by the addition of dimethyl sulfoxide (DMSO). On the basis of the conformational change of subtilisin Carlsberg observed by FT-IR, CD, and fluorescence spectra, the DMSO-induced high enantioselectivity could be related to a partial decrease of subtilisin's tertiary structure. This model for the subtilisin's enantiorecognition is also supported by analysis of the specific catalytic constants (Vmax/Km) obtained for each enantiomer of the substrate. In addition, substituent effects on the enantioselectivity for the subtilisin-catalyzed hydrolysis were studied by use of a range of ethyl (RS)-2-(4-substituted phenoxy)propionates as substrates.

Dimethyl sulfoxide-induced high enantioselectivity of subtilisin Carlsberg for hydrolysis of ethyl 2-(4-substituted phenoxy)propionates

The enantioselectivity for subtilisin-catalyzed hydrolysis of ethyl 2-(4-substituted phenoxy)propionates in an aqueous buffer solution was improved by addition of DMSO (54–56% v/v). On the basis of the conformational change of subtilisin Carlsberg observed for FT-IR and CD spectra, the high enantioselectivity for subtilisin-catalyzed hydrolysis of racemic ethyl 2-(4-ethylphenoxy)propionate could be related to a partial decrease of the tertiary structure of the enzyme protein arising from an increase of the ratio of DMSO in the reaction medium. This mechanistic model for the enantiorecognition can also be supported by the discussion based on the value of the Michaelis constant (Km) obtained for each enantiomer of the substrate.