Amano Lipase PS from Burkholderia cepacia- Evaluation of the Effect of Substrates and Reaction Media on the Catalytic Activity

2020 ◽  
Vol 24 (7) ◽  
pp. 798-807
Author(s):  
Jacek Dulęba ◽  
Tomasz Siódmiak ◽  
Michał Piotr Marszałł
Keyword(s):  
Burkholderia Cepacia ◽  
Kinetic Resolution ◽  
Lipolytic Activity ◽  
Reaction Medium ◽  
Building Blocks ◽  
Diisopropyl Ether ◽  
Acyl Donor ◽  
Pseudomonas Cepacia ◽  
Reaction Media ◽  
Isopropenyl Acetate

: Lipases in the native or immobilized form have commonly been used as catalysts in the chemical and pharmaceutical industry. One of the widely available enzyme catalysts on the market is lipase from Burkholderia cepacia (BCLs), previously called Pseudomonas cepacia (PCLs). This enzyme is applied, among others, in the stereoselective acylation of molecules to achieve chiral pure enantiomers of drugs or their building blocks. In this study, Amano lipase PS (APS-BCL), which is a commercial lipase from Burkholderia cepacia (BC) was tested. The lipolytic activity of APS-BCL by hydrolysis of vegetable oils and enantioselective activity of APS-BCL by the kinetic resolution of (R,S)-1-phenylethanol with using isopropenyl acetate as an acyl donor were evaluated. An effect of reaction media with different logP values (t-butyl methyl ether, dichloromethane, diisopropyl ether, toluene, cyclohexane, n-hexane, isooctane and n-heptane) on the enantioselective activity of lipase was also studied. The high value of the enantiomeric ratio (E =308.5) with the utilization of isopropenyl acetate was achieved. Whereas, the best reaction medium turned out to be diisopropyl ether, C =47.9%, eep =98%, ees =90%, after 24 h of incubation. Moreover, the influence of ω6/ω9 polyunsaturated fatty acids (PUFAs) ratio in commercial (peanut, camelina, rape, pumpkin seed, walnut, sesame, avocado, rice, corn, black cumin, hemp, safflower, grape seed) oils was investigated for the lipase activity. For the first time, the cut-off limit of ω6/ω9 ratio was proposed. The ratio equal to or higher than 2.3 allows achieving higher lipolytic activity.

Fluorous Phases and Compressed Carbon Dioxide as Alternative Solvents for Chemical Synthesis: A Comparison

2004 ◽  
Author(s):  
Walter Leitner
Keyword(s):  
Carbon Dioxide ◽  
Chemical Synthesis ◽  
High Throughput Screening ◽  
Large Scale ◽  
Ecological Impact ◽  
Reaction Medium ◽  
Building Blocks ◽  
Liquid Phases ◽  
Synthetic Procedure ◽  
Reaction Media

The principal goal of basic research in chemical synthesis is the development of efficient tools for functional group transformations and for the assembly of building blocks during the construction of molecules with increasing complexity. Traditionally, new approaches in this area have focused on the quest for new reaction pathways, reagents, or catalysts. Comparably less effort has been devoted to utilize the reaction medium as a strategic parameter, although the use of solvents is often crucial in synthetically useful transformations. The first choice for a solvent during the development of a synthetic procedure is usually an organic liquid, which is selected on the basis of its protic or aprotic nature, its polarity, and the temperature range in which the reaction is expected to proceed. Once the desired transformation is achieved, yield and selectivity are further optimized in the given medium by variation of temperature, concentration, and related process parameters. At the end of the reaction, the solvent must be removed quantitatively from the product using conventional workup techniques like aqueous extraction, distillation, or chromatography. If the synthetic procedure becomes part of a large-scale application, the solvent can sometimes be recycled, but at least parts of it will ultimately end up in the waste stream of the process. Increasing efforts to develop chemical processes with minimized ecological impact and to reduce the emission of potentially hazardous or toxic organic chemicals have stimulated a rapidly growing interest to provide alternatives to this classical approach of synthesis in solution. At the same time, researchers have started to realize that the design and utilization of multifunctional reaction media can add a new dimension to the development of synthetic chemistry. In particular, efficient protocols for phase separations and recovery of reagents and catalysts are urgently required to provide innovative flow schemes for environmentally benign processes or for high-throughput screening procedures. Fluorous liquid phases and supercritical carbon dioxide (sc CO2) have received particular attention among the various reaction media that are discussed as alternatives to classical organic solvents. The aim of this chapter is to compare these two media directly and to critically evaluate their potential for synthetic organic chemistry.

scholarly journals Biocatalytic synthesis of (S)-Practolol, a selective β-blocker

Biocatalysis ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Sachin Mulik ◽  
Saptarshi Ghosh ◽  
Jayeeta Bhaumik ◽  
Uttam C. Banerjee
Keyword(s):  
Adrenergic Receptor ◽  
Kinetic Resolution ◽  
Sol Gel ◽  
Enantiomeric Excess ◽  
Green Technology ◽  
Chemoenzymatic Synthesis ◽  
Acyl Donor ◽  
Pseudomonas Cepacia ◽  
Reaction Parameters ◽  
Β Blocker

AbstractThe present study describes an efficient chemoenzymatic synthesis of enantiopure (S)-Practolol, a selective β-adrenergic receptor blocker. Prior to the synthesis of the target, a synthetic protocol for (RS)-N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide, an essential precursor, was developed. Various commercial lipases were screened for the kinetic resolution of (RS)- N-4-(3-chloro-2-hydroxypropoxy)phenylacetamide using toluene as solvent and vinyl acetate as an acyl donor. Among various lipases screened, Pseudomonas cepacia sol-gel AK showed the highest enantioselectivity (96% enantiomeric excess with 50% conversion), affording (S)-1-(4-acetamidophenoxy)-3-chloropropan-2-yl acetate. Optimization of the reaction parameters was carried out in order to find the best-suited conditions for the biocatalysis. Furthermore, the enantiopure intermediate was hydrolyzed and the resulting product was reacted with isopropylamine to afford (S)-Practolol. This biocatalytic procedure depicts a green technology for the synthesis of (S)-Practolol with better yield and enantiomeric excess.

scholarly journals Synthesis of water-soluble surfactants using catalysed condensation polymerisation in green reaction media

2021 ◽  
Author(s):  
Amy R. Goddard ◽  
Edward A. Apebende ◽  
Joachim C. Lentz ◽  
Kim Carmichael ◽  
Vincenzo Taresco ◽  
...  
Keyword(s):  
Reaction Medium ◽  
Building Blocks ◽  
Water Soluble ◽  
Temperature Sensitive ◽  
Soluble Surfactants ◽  
Surface Active ◽  
Reaction Media

Synthesis and characterisation of novel linear surface-active polymers from temperature sensitive renewable building blocks using an inexpensive catalyst and clean scCO2 as reaction medium.

Water content influences the selectivity of CALB-catalyzed kinetic resolution of phenoxymethyl-substituted secondary alcohols

2002 ◽  
Vol 80 (6) ◽  
pp. 577-581 ◽  
Author(s):  
Elisabeth Egholm Jacobsen ◽  
Thorleif Anthonsen
Keyword(s):  
Water Content ◽  
Water Activity ◽  
Kinetic Resolution ◽  
Relative Rate ◽  
High Water ◽  
High Water Content ◽  
Acyl Donor ◽  
Acyl Donors ◽  
Reaction Media ◽  
Derivatives Of

Derivatives of 1-phenoxy-2-alkanols were kinetically resolved by esterification with irreversible and reversible acyl donors using lipase B from Candida antarctica (Novozyme 435) as a catalyst. To optimize the relative rate of reaction (the E-value), esterifications in eight different solvents with different water activities were performed. For 3-bromo-1-phenoxy-2-propanol (1), the E-values in all the solvents were higher when the water activity was increased, while the E-values for 1-phenoxy-2-pentanol (2) and 3-chloro-1-phenoxy-2-propanol (3) decreased by increasing water activity. The water content of the various reaction media with the same water activity was determined. Solvents such as 1,4-dioxane, acetonitrile, and tetrahydrofuran contained much more water than hexane, carbon tetrachloride, cyclohexane, toluene, and benzene. At high-water activity, the high-water content of the former group of solvents resulted in termination of the reaction at low conversion. The reason seemed to be that the acyl donor and possibly also the produced esters were hydrolyzed. This was not the case when the esterification was performed in water-immiscible solvents with the same water activity.Key words: kinetic resolution, E-value, solvents, water activity, water content.

scholarly journals Lipase Catalyzed Synthesis of Enantiopure Precursors and Derivatives for β-Blockers Practolol, Pindolol and Carteolol

Catalysts ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 503
Author(s):  
Morten Gundersen ◽  
Guro Austli ◽  
Sigrid Løvland ◽  
Mari Hansen ◽  
Mari Rødseth ◽  
...  
Keyword(s):  
Building Block ◽  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Catalytic Amount ◽  
Building Blocks ◽  
Β Blocker ◽  
Β Blockers ◽  
Optical Rotations ◽  
Reported Data ◽  
By Products

Sustainable methods for producing enantiopure drugs have been developed. Chlorohydrins as building blocks for several β-blockers have been synthesized in high enantiomeric purity by chemo-enzymatic methods. The yield of the chlorohydrins increased by the use of catalytic amount of base. The reason for this was found to be the reduced formation of the dimeric by-products compared to the use of higher concentration of the base. An overall reduction of reagents and reaction time was also obtained compared to our previously reported data of similar compounds. The enantiomers of the chlorohydrin building blocks were obtained by kinetic resolution of the racemate in transesterification reactions catalyzed by Candida antarctica Lipase B (CALB). Optical rotations confirmed the absolute configuration of the enantiopure drugs. The β-blocker (S)-practolol ((S)-N-(4-(2-hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) was synthesized with 96% enantiomeric excess (ee) from the chlorohydrin (R)-N-(4-(3-chloro-2 hydroxypropoxy)phenyl)acetamide, which was produced in 97% ee and with 27% yield. Racemic building block 1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol for the β-blocker pindolol was produced in 53% yield and (R)-1-((1H-indol-4-yl)oxy)-3-chloropropan-2-ol was produced in 92% ee. The chlorohydrin 7-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, a building block for a derivative of carteolol was produced in 77% yield. (R)-7-(3-Chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one was obtained in 96% ee. The S-enantiomer of this carteolol derivative was produced in 97% ee in 87% yield. Racemic building block 5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one, building block for the drug carteolol, was also produced in 53% yield, with 96% ee of the R-chlorohydrin (R)-5-(3-chloro-2-hydroxypropoxy)-3,4-dihydroquinolin-2(1H)-one. (S)-Carteolol was produced in 96% ee with low yield, which easily can be improved.

Enzymatic synthesis of a chiral chalcogran intermediate

2014 ◽  
Vol 68 (6) ◽  
Author(s):  
Vladimír Mastihuba ◽  
Pavel Čepec ◽  
Silvia Vlčková ◽  
Erika Farkašová ◽  
Mária Mastihubová ◽  
...  
Keyword(s):  
Vinyl Acetate ◽  
Bark Beetle ◽  
Enzymatic Synthesis ◽  
Kinetic Resolution ◽  
Thermomyces Lanuginosus ◽  
Methyl Tert Butyl Ether ◽  
Lipozyme Tl Im ◽  
Butyl Ether ◽  
Novozyme 435 ◽  
Reaction Media

AbstractTwo lipases, Novozyme 435 (lipase B from Candida Antarctica) and Lipozyme TL IM (Thermomyces lanuginosus) were used successfully for the kinetic resolution of racemic 1-(2-furyl)-3-pentanol, the key intermediate in synthesis of the bark beetle pheromone, chalcogran. The desired S-(+)-enantiomer was prepared in enantiomeric excesses higher than 98 % and with yields of 26.3 % and 32.5 %, respectively. Methyl tert-butyl ether and vinyl acetate were found to be the best reaction media and the acetyl donor to achieve fast and effective resolution.

Sintesis dan Karakterisasi Na-CMC dari A-Selulosa Serabut Kelapa Sawit

2021 ◽  
Vol 1 (9) ◽  
pp. 375-381
Author(s):  
Indriani Indriani ◽  
Abu Hasan ◽  
Anerasari Meydinariasty
Keyword(s):  
Palm Oil ◽  
Trichloroacetic Acid ◽  
Reaction Medium ◽  
Synthesis Process ◽  
Optimal Composition ◽  
Palm Fiber ◽  
Oil Processing ◽  
Reaction Media ◽  
By Products

Na-CMC adalah eter polimer selulosa linier yang digunakan sebagai bahan pengental, pengemulsi dan penstabil. Salah satu bahan dasar pembuatan Na-CMC yaitu serabut kelapa sawit. Serabut kelapa sawit merupakan salah satu hasil samping terbesar yang dihasilkan dalam proses pengolahan minyak kelapa sawit dan dapat dapat dijadikan sebagai sumber selulosa karena mengandung selulosa hingga 59,60%. Tujuan dari penelitian ini untuk mendaptakan komposisi optimal campuran media reaksi isopropanol-etanol dan konsentrasi asam trikloroasetat serta konsentrasi NaOH dengan memvariasikan komposisi media reaksi isopropanol-etanol menjadi 20:80; 40:60; 50:50; 60:40 dan 80:20, sedangkan untuk konsentrasi asam trikloroasetat yaitu 15%, 20% san 25% dan untuk konsentrasi NaOH adlah 15% dan 20%. Didapat bahwa  komposisi optimal media reaksi pada proses sintesis Na-CMC terdapat pada campuran isopropanol-etanol 80:20 dengan konsentrasi asam trikloroasetat 25% dan konsentrasi NaOH 20% menghasilkan nilai DS yang tertinggi yaitu sebesar 0,8124 dengan kemurnian dan pH berturut-turut sebesar 99,68% dan 7,9.   Na-CMC is a linear cellulose polymer ether used as a thickener, emulsifier and stabilizer. One of the basic ingredients for making Na-CMC is palm fiber. Palm fiber is one of the largest by-products produced in the palm oil processing process and can be used as a source of cellulose because it contains up to 59.60% cellulose. The purpose of this study was to obtain the optimal composition of the isopropanol-ethanol reaction media mixture and the concentration of trichloroacetic acid and NaOH concentration by varying the composition of the isopropanol-ethanol reaction medium to 20:80; 40:60; 50:50; 60:40 and 80:20, while the concentrations of trichloroacetic acid were 15%, 20% and 25% and the concentrations of NaOH were 15% and 20%, respectively. It was found that the optimal composition of the reaction medium in the Na-CMC synthesis process was found in a mixture of isopropanol-ethanol 80:20 with a concentration of 25% trichloroacetic acid and 20% NaOH concentration resulting in the highest DS value of 0.8124 with purity and pH respectively. 99.68% and 7.9.

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