Hydrolytic enzymatic transformation of advanced synthetic intermediates: on the choice of the organic cosolvent

Berkowitz, David B.; Hartung, Ryan E.; Choi, Sungjo

doi:10.1016/s0957-4166(99)00509-1

Cited by 14 publications

(7 citation statements)

References 14 publications

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“…In addition, these two solutions showed negligible impact on the enzyme stability. Berkowitz et al 324 suggested that 10% triglyme in aqueous buffer solution enabled the optimal efficiency for a PPL-catalyzed hydrolysis of a drug intermediate at both lower enzyme loading and higher temperature. Schroën et al 325 studied the enzymatic synthesis of antibiotic cephalexin catalyzed by penicillin G acylase (Scheme 44), and found the enzyme retained 90% activity after incubation in 30–36% (v/v) glymes (mono-, di- and tri-) at 30 °C for 24 h; comparing with the direct synthesis in water, the addition of methanol and triglyme could increase the equilibrium concentration of cephalexin by a factor of 2–3.…”

Section: (Co-)solvents For Biocatalysismentioning

confidence: 99%

Glymes as versatile solvents for chemical reactions and processes: from the laboratory to industry

2014

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Glymes, also known as glycol diethers, are saturated non-cyclic polyethers containing no other functional groups. Most glymes are usually less volatile and less toxic than common laboratory organic solvents; in this context, they are more environmentally benign solvents. However, it is also important to point out that some glymes could cause long-term reproductive and developmental damages despite their low acute toxicities. Glymes have both hydrophilic and hydrophobic characters that common organic solvents are lack of. In addition, they are usually thermally and chemically stable, and can even form complexes with ions. Therefore, glymes are found in a broad range of laboratory applications including organic synthesis, electrochemistry, biocatalysis, materials, and Chemical Vapor Deposition (CVD), etc. In addition, glyme are used in numerous industrial applications, such as cleaning products, inks, adhesives and coatings, batteries and electronics, absorption refrigeration and heat pumps, as well as pharmaceutical formulations, etc. However, there is a lack of comprehensive and critical review on this attractive subject. This review aims to accomplish this task by providing an in-depth understanding of glymes’ physicochemical properties, toxicity and major applications.

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Section: (Co-)solvents For Biocatalysismentioning

confidence: 99%

Glymes as versatile solvents for chemical reactions and processes: from the laboratory to industry

2014

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“…35 A few studies observed high enzyme activities and/or stabilities in aqueous glymes. [36][37][38][39] Our group 40 found that long-chain glymes are highly compatible with immobilized Candida antarctica lipase B.…”

Section: Introductionmentioning

confidence: 99%

DNA-based asymmetric catalysis: role of ionic solvents and glymes

Zhao

Shen

2014

RSC Adv.

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Recently, DNA has been evaluated as a chiral scaffold for metal complexes to construct so called ‘DNA-based hybrid catalysts’, a robust and inexpensive alternative to enzymes. The unique chiral structure of DNA allows the hybrid catalysts to catalyze various asymmetric synthesis reactions. However, most current studies used aqueous buffers as solvents for these asymmetric reactions, where substrates/products are typically suspended in the solutions. The mass transfer limitation usually requires a long reaction time. To overcome this hurdle and to advance DNA-based asymmetric catalysis, we evaluated a series of ionic liquids (ILs), inorganic salts, deep eutectic solvents (DES), glymes, glycols, acetonitrile and methanol as co-solvents/additives for the DNA-based asymmetric Michael addition. In general, these additives induce indistinguishable changes to the DNA B-form duplex conformation as suggested by circular dichroism (CD) spectroscopy, but impose a significant influence on the catalytic efficiency of the DNA-based hybrid catalyst. Conventional organic solvents (e.g. acetonitrile and methanol) led to poor product yields and/or low enantioselectivities. Most ILs and inorganic salts cause the deactivation of the hybrid catalyst except 0.2 M [BMIM][CF3COO] (95.4% ee and 93% yield) and 0.2 M [BMIM]Cl (93.7% ee and 89% yield). Several other additives have also been found to improve the catalytic efficiency of the DNA-based hybrid catalyst (control reaction without additive gives >99% ee and 87% yield): 0.4 M glycerol (>99% ee and 96% yield at 5 °C or 96.2% ee and 83% yield at room temperature), 0.2 M choline chloride/glycerol (1:2) (92.4% ee and 90% yield at 5 °C or 94.0% ee and 88% yield at room temperature), and 0.5 M dipropylene glycol dimethyl ether (>99% ee and 87% yield at room temperature). The use of some co-solvents/additives allows the Michael addition to be performed at a higher temperature (e.g. room temperature vs 5 °C) and a shorter reaction time (24 h vs 3 days). In addition, we found that a brief pre-sonication (5 min) of DNA in MOPS buffer prior to the reaction could improve the performance of the DNA-based hybrid catalyst. We have also shown that this DNA-based catalysis method is suitable for a variety of different substrates and relatively large-scale reactions. In conclusion, a judicious selection of benign co-solvents/additives could improve the catalytic efficiency of DNA-based hybrid catalyst.

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“…Organic solvents are often required to increase the solubility of the hydrophobic substrate, alter the thermodynamic equilibrium to promote synthesis, and inhibit water-dependent side reactions. But rapid denaturation of enzymes occurs when the volume fraction of most water-miscible solvents exceeds 20-50% (v/v) [29]. Therefore, the isopropanol concentration in the reaction medium is the certain issue of the asymmetric reduction.…”

Section: Discussionmentioning

confidence: 99%

Efficient Biocatalytic Preparation of Optically Pure (R)-1-[4-(Trifluoromethyl)phenyl]ethanol by Recombinant Whole-Cell-Mediated Reduction

Chen¹,

Xia²,

Liu³

et al. 2019

Catalysts

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(R)-1-[4-(Trifluoromethyl)phenyl]ethanol is an important pharmaceutical intermediate of a chemokine CCR5 antagonist. In the present study, a bioprocess for the asymmetric reduction of 4-(trifluoromethyl)acetophenone to (R)-1-[4-(trifluoromethyl)phenyl]ethanol was developed by recombinant Escherichia coli cells with excellent enantioselectivity. In order to overcome the conversion limitation performed in the conventional buffer medium resulting from poor solubility of non-natural substrate, we subsequently established a polar organic solvent-aqueous medium to improve the efficacy. Isopropanol was selected as the most suitable cosolvent candidate, based on the investigation on a substrate solubility test and cell membrane permeability assay in different organic solvent-buffer media. Under the optimum conditions, the preparative-scale asymmetric reduction generated a 99.1% yield with >99.9% product enantiomeric excess (ee) in a 15% (v/v) isopropanol proportion, at 100 mM of 4-(trifluoromethyl)acetophenone within 3 h. Compared to bioconversion in the buffer medium, the developed isopropanol-aqueous system enhanced the substrate concentration by 2-fold with a remarkably improved yield (from 62.5% to 99.1%), and shortened the reaction time by 21 h. Our study gave the first example for a highly enantioselective production of (R)-1-[4-(trifluoromethyl)phenyl]ethanol by a biological method, and the bioreduction of 4-(trifluoromethyl)acetophenone in a polar organic solvent-aqueous system was more efficient than that in the buffer solution only. This process is also scalable and has potential in application.

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Hydrolytic enzymatic transformation of advanced synthetic intermediates: on the choice of the organic cosolvent

Cited by 14 publications

References 14 publications

Glymes as versatile solvents for chemical reactions and processes: from the laboratory to industry

Glymes as versatile solvents for chemical reactions and processes: from the laboratory to industry

DNA-based asymmetric catalysis: role of ionic solvents and glymes

Efficient Biocatalytic Preparation of Optically Pure (R)-1-[4-(Trifluoromethyl)phenyl]ethanol by Recombinant Whole-Cell-Mediated Reduction

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