Esterification In Organic Solvents Research Articles

Enzymatic synthesis of tyrosol esters in organic solvents and ionic liquids: Correlation between enzyme activity and solvent properties

Tyrosol is a principle phenolic compound present in olive oil and wine with great pharmacological potentials due to its strong antioxidant property. Its application can be highly extended by increasing its lipophilicity through esterification. In this study, tyrosol esters were synthesized by enzymatic transesterification of tyrosol with vinyl esters, with a commercial lipase from Novozymes (Novozym 435, Candida antarctica lipase B (CALB) immobilized on macroporous acrylic resin beads) as the catalyst, both in organic solvents and in ionic liquids. Methyl tert-butyl ether (MTBE) was the best solvent, offering complete conversions towards the synthesis of tyrosol esters with varying chain lengths (C2-C18) within 1 h. Taking the enzymatic transesterification between tyrosol and vinyl acetate as the model reaction, 18 organic solvents and 24 ionic liquids were screened, and their solvent properties (i.e. hydrophobicity, polarity, viscosity, water activity, and partition coefficients of substrate and product) were correlated to the enzyme activity. Upon enzyme screening, four new lipases were found to be highly efficient, relative to the best-performed Novozym 435 and Lipozyme TLIM (Thermomyces lanuginosus lipase (TLL) immobilized on silica gel), in tyrosol ester synthesis. This work provides enzymatic methods of esterifying tyrosol that are much more efficient than those reported in literature, and will shed light on re-consideration of the roles of solvents in nonaqueous enzymology.

Crossing the Solubility Rubicon: 15-Crown-5 Facilitates the Preparation of Water-Soluble Sulfo-NHS Esters in Organic Solvents.

The Sulfo-NHS ester is a mainstay reagent for facilitating amide bond formation between carboxylic acids and amine functionalities in water. However, the preparation of Sulfo-NHS esters currently requires hydrophobic carboxylic acids, which are poorly water-soluble, to first be reacted with the N-hydroxysulfosuccinimide sodium salt, which is insoluble in organic solvents. The mutually incompatible solvation requirements thus complicate the synthesis of Sulfo-NHS esters. As a simple, rapid, and cost-effective solution to this problem, we report that the use of 15-crown-5 to complex the sodium cation of N-hydroxysulfosuccinimide sodium salt circumnavigates these solvation incompatibility issues by rendering the N-hydroxysulfosuccinimide salt soluble in organic solvents, resulting in a cleaner esterification reaction and thus improved yields of activated ester product. We also demonstrate that the resultant "crowned" Sulfo-NHS-ester remains water-soluble and is no less reactive than its classic "uncrowned" Sulfo-NHS counterpart when used in bioconjugation reactions between protein amine-functionalities and hydrophobic carboxylic acids.

Isolation and Identification of Thermophilic Bacteria from Lahendong Hot Spring, North Sulawesi

Thermophilic bacteria are a group of procaryotic organisms that can grow in high temperature around 450C until 900C. Thermophilic bacteria are able to produce lipase thermostable enzyme. Lipase thermostable enzymes produced from thermophilic bacteria are able to catalyze the hydrolysis of triglycerides into glycerol and free fatty acids and the synthesis of esters in organic solvents. Lipase thermostable enzymes are potential to be used in industrial production. Lipase enzymes have been used for the production of laundry detergents as additives or to replace chemical detergents because of their environmental friendliness. This research was aimed to isolates and identified themophilic bacteria from Lahendong hot springs, North Sulawesi and to conduct the morphological characterization, biochemical test, and molecular identification with 16S rRNA. Results showed that isolates obtained from the- Lahendong hot spring have high similarities with Geobacillus kaustophilus, Bacillus cereus, and Geobacillus lituanicus. The three isolates are able to produce lipase thermostbale enzyme.

Copolymerization of N-[3-dialkylaminopropyl]methacrylamides with acrylic amides and esters in organic solvents

The radical copolymerization of N-[3-(dialkylamino)-propyl]methacrylamides with a number of (meth)acrylic amides and esters in organic solvents over a wide range of molar ratios has been studied. Co-polymerisation constants for five polymerisation systems in 1,4-dioxane and toluene have been determined by the Feinman and Ross method. The influence of the solvent on the kinetics of the copolymerization of the studied monomers was found, which manifests itself in a change of the reactivity ratios of the monomers upon varying the polarity of the medium. For the obtained polymers, the presence of thermosensitive properties in aqueous solutions and the effect of the concentration and composition of copolymers on their solubility in water were shown.

Chiral Recognition of Amino Acid Esters in Organic Solvents Using a Glucose-Based Receptor.

Due to the chemical and biological relevance of amino acids, efficient methods for the recognition and separation of their enantiomers are highly sought after. Chiral receptors based on extended molecular scaffolds are typically employed for this purpose. These receptors are often effective only in specific environments and towards a narrow scope of amino acid guests. Recently we reported a simple, glucose-based macrocycle capable of enantioselective binding of a broad range of amino acid methyl esters in water. Herein we demonstrate that the same receptor can be used for chiral recognition of amino acid esters in organic solvents. We show that the binding affinity and selectivity of the receptor are highly dependent on the coordinating strength of the solvent. An in-depth analysis of the receptor’s conformation and its interactions with amino acid methyl esters allowed us to propose a binding mode of amino acids to the receptor in CDCl3. The binding modes in CDCl3 and D2O were then compared, highlighting the main interactions responsible for binding affinity and selectivity in each solvent. We envision that the insight provided by this study will facilitate the development of further amino acid receptors based on monosaccharides with improved binding affinities and both enantio- as well as chemoselectivities.

Equilibria in the 3-(trifluoromethyl)phenylboronic acid - boroxine system. Solubility of the acid and its cyclic esters in organic solvents

Solubilities of 3-(trifluoromethyl)phenylboronic acid, its pinacol ester and azaester in organic solvents have been determined experimentally by a dynamic method. The disappearance of turbidity was determined by measuring light intensity using a luminance probe. The title acid easily dehydrates with the formation of a considerable amount of the corresponding boroxine. The dehydration proceeds both in the solid state as well as in solutions. The process was investigated using various techniques (NMR, Raman, differential scanning calorimetry, thermogravimetric analysis and powder X-ray diffraction). The possibilities of using above methods to describe the acid-boroxine equilibria was assessed. The title acid displays high solubility in 3-pentanone, moderate in chloroform and very low in methylcyclohexane. Its pinacol ester and azaester derivatives show better solubility than the parent acid in all tested solvents. For pinacol ester, differences between particular solvents are small, while for azaester they are significant. In this case the highest solubility is observed in chloroform and the lowest in methylcyclohexane. The solubilities of pinacol ester and azaester have been correlated by some GE-models.

Solubility of Phenylboronic Acid and its Cyclic Esters in Organic Solvents

The solubilities of phenylboronic acid, its pinacol ester and azaester in organic solvents (chloroform, 3-pentanone, acetone, dipropyl ether and methylcyclohexane) have been determined experimentally by a dynamic method, in which the disappearance of turbidity was determined by measuring of light intensity using a luminance probe. Phenylboronic acid has high solubility in ether and ketones, moderate in chloroform and very low in hydrocarbon. Pinacol ester and azaester show better solubility than the parent acid in all tested solvents. For pinacol ester differences between particular solvents are small, while for azaester the differences are significant. For both esters the highest solubility is observed in chloroform and the lowest in the hydrocarbon. The results have been correlated by the Wilson, NRTL and Redlich–Kister equations. For the phenylboronic acid better correlation of the data is obtained by polynomials in comparison with the above equations. It is connected with additional acid-anhydride equilibrium in the system. The influence of polarity of the solvents on the solubility is discussed.

Catalytic Performance of a Robust Whole-Cell Biocatalyst in the Regioselective Synthesis of Helicid Esters Under Optimized Processing Conditions

In this study, lyophilized Pseudomonas aeruginosa based whole-cell biocatalyst was used in the highly efficient and regioselective acylation of helicid with fatty acid vinyl esters in organic solvents. P. aeruginosa whole-cell catalyst showed high biomass and biocatalytic performance using 0.1% (w/v) soybean oil and 0.2% (w/v) tryptone as the carbon and nitrogen source, respectively. The biomass (0.72 g/L) cultivated for 36 h under the optimized conditions was 2-folds higher than that obtained by the use of the initial conditions (0.36 g/L). In addition, the optimized medium was found to be suitable for P. aeruginosa cultured in 3.5-L scale fermentation with high biomass (0.71 g/L) obtained at 24 h. Besides, a high substrate conversion efficiency (ranged from 92 to 99%) and excellent regioselectivity (99%) was achieved when P. aeruginosa whole-cell biocatalyst was applied to synthesize an array of 6′-esters of helicid. The reaction rate varies with varying acyl donors because of their differential interactions with the catalytic site of the enzyme from the whole cells of P. aeruginosa. Taken together, P. aeruginosa whole-cell catalyst obtained using optimal culture medium manifest a promising and highly-regioselective alternative to purified enzymes for the regioselective formation of 6′-esters derivatives of helicid in non-aqueous solvents.

Enantioselective esterification of (R,S)-2-(4-methylphenyl) propionic acid via Novozym 435: Optimization and application

This paper reports on the resolution of ( R,S )-2-(4-methylphenyl) propionic acid (MPPA) enantiomers by enzymatic esterification in organic solvent. Novozym 435 (CALB) has the best catalytic performance compared with other lipases. Of the alcohols screened, n -hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n -hexane. Response surface methodology (RSM) was used to evaluate the influence of the factors, such as temperature, enzyme amount, substrate concentration and reaction time on the substrate conversion ( c ) and enantiomeric excess (ee). The correlation coefficient R 2 for enantiomeric excess and the conversion are 0.9827 and 0.9910, respectively, indicating that can accurately predict the experimental results. By simulation and optimization, the optimal conditions were obtained, involving 600 mmol·L −1 MPPA concentration (0.60 mmol), 850 mmol·L −1 hexanol concentration (0.85 mmol), 58 mg enzyme amount, 75 °C temperature and 4.5 h reaction time, respectively. Under the optimized conditions, the experimental values of conversion and enantiomeric excess were 89.34% and 97.84%, respectively, which are in good agreement with the model predictions.

Lipase‐catalyzed synthesis of glucose‐6‐O‐hexanoate in deep eutectic solvents

Enzymatic synthesis of sugar fatty acid esters in organic solvents is a well‐described procedure to synthesize glycolipids. This study aims at replacing these solvents with deep eutectic solvents (DES), a group of solvents that gained more and more interest during the last years, since they can be easily produced from non‐toxic resources. Enzymatic glycolipid synthesis in deep eutectic solvents was investigated, employing Candida antarctica lipase B (Novozyme 435) in various deep eutectic solvents. A successful lipase‐catalyzed synthesis of glucose fatty acid esters gave proof of this concept, while using the two deep eutectic solvents consisting of choline chloride and urea (CC : U) and choline chloride and glucose (CC : Glc). Additionally the DES consisting of choline chloride and glucose was observed to act as solvent and substrate for the synthesis at the same time.Practical applicationsGlycolipids find applications in many everyday products like cosmetic and pharmaceutical formulations, food and classic cleaning products, utilizing their good detergent or emulsification properties. Glycolipids can, among other routes, be synthesized via lipase‐catalyzed reactions, which are often carried out in organic solvents. By replacing these organic solvents with more ecologically friendly solvents like deep eutectic solvents, the reaction might be improved and the amount of waste produced could be reduced.The lipase‐catalyzed synthesis of glucose‐6‐O‐hexanoate employing glucose and vinyl hexanoate in different deep eutectic solvents was demonstrated within the manuscript.

Lipases in the Regioselective Preparation of Glyceric Acid Esters of Methyl Glycosides

AbstractThe lipase‐catalyzed regioselective acylation of methyl α‐D‐galacto‐, ‐gluco‐ and ‐mannopyranosides with isopropylidene‐protected (R)‐ and (S)‐glyceric acid methyl esters in organic solvents is presented. Factors affecting the formation of the 6‐O‐mono‐ and 2,6‐O‐diacylated products are examined and preparative‐scale reactions are detailed. In addition, studies on partially protected methyl α‐D‐galactopyranosides are presented, with the 3,4‐O‐isopropylidene protected compound leading exclusively to the formation of the 6‐O‐monoacylated product even at high substrate concentrations. Application of acidic resin in methanol allows removal of the isopropylidene protection groups without disturbing the ester bond at C‐6.

Recent Lipase-Catalyzed Hydrolytic Approaches to Pharmacologically Important β-and γ-Amino Acids

Kinetic and sequential kinetic enzymatic routes for the synthesis of enantiomeric β- and γ-amino acids through enzymatic ring cleavage of the corresponding lactams in organic solvents or solvent-free systems or a supercritical CO(2) medium, and for the enantioselective hydrolysis of the corresponding amino esters in organic solvents are reviewed. In the frame of a practical guide, a simple and rapid GC enantioseparation technique for amino acids, including exact descriptions of selected enzymatic reactions, is additionally presented.

Recent Lipase-Catalyzed Hydrolytic Approaches to Pharmacologically Important β-and λ-Amino Acids

Kinetic and sequential kinetic enzymatic routes for the synthesis of enantiomeric β- and λ-amino acids through enzymatic ring cleavage of the corresponding lactams in organic solvents or solvent-free systems or a supercritical CO2 medium, and for the enantioselective hydrolysis of the corresponding amino esters in organic solvents are reviewed. In the frame of a practical guide, a simple and rapid GC enantioseparation technique for amino acids, including exact descriptions of selected enzymatic reactions, is additionally presented. Keywords: β-amino acid, λ-amino acid, β-amino ester, burkholderia cepacia lipase PS, candida antarctica lipase B, enantiomer, enzymatic catalysis, GC enantioseparation, kinetic resolution, β-lactam, λ-lactam, lipase, organic solvent, sequential resolution, solvent-free system, supercritical CO2.

Chemical and thermal characterization of three industrial lignins and their corresponding lignin esters

Corn stover and rice straw lignin samples received from ethanol pilot plants, along with softwood kraft lignin samples, were characterized using pyrolysis GC-MS, 13C CP/MAS NMR spectroscopy, and permanganate oxidation degradation. The lignins were then esterified using 1-methylimidazole as a catalyst in a pyridine-free reaction, and the thermal properties of the products were evaluated. Solid state NMR showed the rice straw lignin contained 18% residual polysaccharides. Pyrolysis GC-MS showed the softwood kraft, corn stover, and rice straw lignins to be G – type, H/G/S – type, and G/S – type, respectively. However, some discrepancy was apparent between the pyrolysis and permanganate oxidation studies as to the ratios of the monomeric make-up of the lignins. The kraft and rice straw lignins were determined to have high degrees of condensation, while the corn stover lignin was uncondensed. Little to no increase in solubility was noticed for corn stover or rice straw lignin esters in organic solvents. Glass transition temperatures (Tg) of the lignin derivatives were determined by a combination of differential scanning calorimetry, dynamic mechanical analysis, and parallel plate rheometry.

Solubilities of Cinnamic Acid Esters in Organic Solvents

The solubilities of three cinnamic acid esters, namely, methyl ferulate, methyl p-coumarate, and methyl sinapate, have been measured in tert-butanol, tert-pentanol, ethyl acetate, and n-hexane, at the temperature range of (303.15 to 321.15) K. It is shown that tert-pentanol is the best solvent for methyl p-coumarate and methyl ferulate and ethyl acetate for methyl sinapate, while the nonpolar n-hexane is the worst solvent. Using the experimentally measured solubilities, the thermodynamic properties of dissolution of the three esters have been calculated. To better understand the solubilization process, the melting temperatures and the enthalpies of fusion of the three esters were determined by differential scanning calorimetry. Finally, successful correlation of the experimental data was achieved with the UNIQUAC and the nonrandom two-liquid (NRTL) activity coefficient models.

Lipase‐catalyzed synthesis of fatty acid sugar ester using extremely supersaturated sugar solution in ionic liquids

The low solubility of sugars has hampered the lipase-catalyzed synthesis of fatty acid sugar esters in organic solvents and ionic liquids (ILs), because several solvents that are able to effectively dissolve sugars are detrimental to enzymes. In this work, in order to prepare a high concentration of sugars in ILs, we have developed a new procedure that entails mixing an aqueous sugar solution into ILs followed by removal of the water from the solution. The glucose concentrations in the supersaturated [Emim][TfO] and [Bmim][TfO] were 19 and 10 times higher, respectively, than the solubilities (6.1 and 4.8 g/L) of glucose in the ILs at 25 degrees C. Furthermore, the supersaturated glucose solutions in ILs were maintained over a long period of time without any significant loss of glucose. In ILs that were extremely supersaturated with glucose, lipase-catalyzed esterifications of glucose with vinyl laurate, and lauric acid were successfully carried out. The conversion increased from 8% to 96% at 1 day of reaction by using supersaturated solution in [Bmim][TfO] which had dissolved glucose concentration of 400% higher than its solubility, compared with the reaction using saturated glucose solution. By making the glucose concentration in ILs much higher than the solubility through our novel and simple method, the initial rate and conversion of the lipase-catalyzed reaction were significantly improved.

Chemoenzymatic approach to enantiopure piperidine-based β-amino esters in organic solvents

This research concentrates on the enantioselectivities of lipase-catalysed reactions with methyl esters of 2-piperidylacetic acid and 3-piperidinecarboxylic acid derivatives. N-Acetylated 2-piperidylacetic acid methyl ester displayed good enantioselectivity ( E = 66) in a 1:1 mixture of diisopropyl ether and butyl butanoate in the presence of lipase PS-C II from Burkholderia cepacia. The reaction is known as interesterification with butyl butanoate rather than alcoholysis with the butanol, because butyl butanoate has to be first hydrolysed or go through alcoholysis with MeOH in order to release butanol. Other N-protective groups (Boc, Ns, Fmoc and Bzn) gave excellent enantioselectivity ( E >200) under the same conditions, and a gram-scale resolution was performed with N-Boc-2-piperidylacetic acid methyl ester. Reaction with a 3-piperidylcarboxylic acid derivative took place with disappointingly low enantioselectivity ( E = 4), with Candida antarctica lipase B being the best of the lipases screened.

Properties of poly(AAc‐co‐HPMA‐cl‐EGDMA) hydrogel‐bound lipase ofPseudomonas aeruginosaMTCC‐4713 and its use in synthesis of methyl acrylate

AbstractMicrobial lipases (E.C. 3.1.1.3) are preferred biocatalysts for the synthesis of esters in organic solvents. Various extracellular thermoalkaliphilic lipases have been reported fromPseudomonassp. In the present study, a purified alkaline thermoalkalophilic extracellular lipase ofPseudomonas aeruginosaMTCC‐4713 was efficiently immobilized onto a synthetic poly(AAc‐co‐HPMA‐cl‐EGDMA) hydrogel by adsorption and the bound lipase was evaluated for its hydrolytic potential towards variousp‐nitrophenyl acyl esters varying in their C‐chain lengths. The bound lipase showed optimal hydrolytic activity towardsp‐nitrophenyl palmitate (p‐NPP) at pH 8.5 and temperature 45°C. The hydrolytic activity of the hydrogel‐bound lipase was markedly enhanced by the presence of Hg2+, Fe3+, and NHsalt ions in that order. The hydrogel‐immobilized lipase (25 mg) was used to perform esterification in variousn‐alkane(s) that resulted in ∼ 84.9 mMof methyl acrylate at 45°C inn‐heptane under shaking (120 rpm) after 6 h, when methanol and acrylic acid were used in a ratio of 100 mM:100 mM, respectively. Addition of a molecular sieve (3Å × 1.5 mm) to the reaction system at a concentration of 100 mg/reaction vol (1 mL) resulted in a moderate enhancement in conversion of reactants into methyl acrylate (85.6 mM). During the repetitive esterification under optimum conditions, the hydrogel‐bound lipase produced 71.3 mMof ester after 10th cycle of reuse. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 183–191, 2007

Chemoenzymatic access to all four enantiopure stereoisomers of 1-ferrocenyl-1,3-butanediol

The kinetic resolution of ferrocenyl aldol 2 was achieved by a lipase-catalyzed esterification in organic solvent. Lipase from Candida antarctica was also found effective in promoting the enantioselective alcoholysis of acetate (±)- 3 with n-BuOH. Both enantiomers of 2 were obtained in enantiopure form and subjected to chemical reduction to afford the corresponding syn- and anti-diols. These diols serve as starting materials for the preparation of new ferrocenyl amino alcohols bearing two stereocenters in the side chain.

D‐Aminoacylase‐Catalyzed Markovnikov Addition of Azoles to Vinyl Esters in Organic Solvents.

AbstractFor Abstract see ChemInform Abstract in Full Text.