Biocatalysis at Extreme Temperatures: Enantioselective Synthesis of both Enantiomers of Mandelic Acid by Transesterification Catalyzed by a Thermophilic Lipase in Ionic Liquids at 120 °C

Abstract

The use of biocatalysts in organic chemistry for catalyzing chemo-, regio- and stereoselective transformations has become an usual tool in the last years, both at lab and industrial scale. This is not only because of their exquisite precision, but also due to the inherent increase in the process sustainability. Nevertheless, most of the interesting industrial reactions involve water-insoluble substrates, so the use of (generally not green) organic solvents is generally required. Although lipases are capable of maintaining their catalytic precision working in those solvents, reactions are usually very slow and consequently not very appropriate for industrial purposes. Increasing reaction temperature would accelerate the reaction rate, but this should require the use of lipases from thermophiles, which tend to be more enantioselective at lower temperatures, as they are more rigid than those from mesophiles. Therefore, the ideal scenario would require a thermophilic lipase capable of retaining high enantioselectivity at high temperatures. In this paper, we describe the use of lipase from Geobacillus thermocatenolatus as catalyst in the ethanolysis of racemic 2-(butyryloxy)-2-phenylacetic to furnish both enantiomers of mandelic acid, an useful intermediate in the synthesis of many drugs and active products. The catalytic performance at high temperature in a conventional organic solvent (isooctane) and four imidazolium-based ionic liquids was assessed. The best results were obtained using 1-ethyl-3-methyl imidazolium tetrafluoroborate (EMIMBF4) and 1-ethyl-3-methyl imidazolium hexafluorophosphate (EMIMPF6) at temperatures as high as 120 °C, observing in both cases very fast and enantioselective kinetic resolutions, respectively leading exclusively to the (S) or to the (R)-enantiomer of mandelic acid, depending on the anion component of the ionic liquid.

Bio-Approach for Obtaining Enantiomerically Pure Clopidogrel with the Use of Ionic Liquids

“…The study verified the possibility of performing the kinetic resolution of racemic clopidogrel carboxylic acid in a two-phase catalytic system using methanol as an acyl acceptor. According to the available literature, it was decided to test five various ionic liquids: [EMIM][EtSO 4 ], [EMIM][MSF 3 ], [HMIM][BF 4 ], [EMIM][BF 4 ], and [DMIM][MeSO 4 ] [ 42 , 43 , 44 , 45 , 46 , 47 ]. The used ionic liquids, however, displayed a variety of kinetic characteristics, leading to varying enantioselectivities and enantiomeric excesses of substrates and products.…”

Applications of Ionic Liquids in Whole-Cell and Isolated Enzyme Biocatalysis

“…Enzyme catalysed processes have also been operated in a mixture of ionic liquids and organic solvents. Lipase from Geobacillus thermocatenolatus performed high temperature (120 °C) enantioselective hydrolysis of racemic 2-(butyryloxy)-2-phenylacetic to mandelic acid in ethanol/[BMIM][BF 4 ] and ethanol/[EMIM][BF 4 ] [ 82 ]. In ethanol/[BMIM][BF 4 ] only ( R -) mendelic acid was formed at 12 h, however, changing the IL mixture to ethanol/[EMIM][BF 4 ] led to ( S -) madelic acid formation after 2.5 h. Lipase- Novozym 435 exhibited higher esterification activity of esculin (a natural phenolic glycosides) with palmitic acid in binary organic-ionic liquid media then the individual ionic liquid and organic solvents [ 83 ].…”

A thermostable organic solvent-tolerant lipase from Brevibacillus sp.: production and integrated downstream processing using an alcohol-salt-based aqueous two-phase system

“…In addition, some reactions are carried out at elevated temperature (Hasan et al, 2006 ; Salihu and Alam, 2015 ; Nezhad et al, 2022 ). This is because catalysis in non-aqueous media offers several advantages, such as increased solubility of hydrophobic substrates in the reaction media, better substrate and product stability, and favoring synthesis over hydrolysis (Cao and Matsuda, 2016 ; Ramos-Martín et al, 2020 ). However, exposure to organic solvents and/or elevated temperature could pose challenges to enzyme activity and stability (Kumar et al, 2016 ; Kikani et al, 2023 ).…”