Advances in deep eutectic solvents and water: applications in metal- and biocatalyzed processes, in the synthesis of APIs, and other biologically active compounds
Owing to a growing awareness towards environmental impact, the search for “greener”, safer, and cost-effective solvents able to replace petroleum-derived solvents has never been greater today. In this context, the use of environmentally responsible solvents like water and the so-called Deep Eutectic Solvents (DESs), constructed from bio-based compounds, has recently experienced important growth in several fields of sciences. This short review highlights the key features of the chemistry of water and (hydrated) DESs when applied to metal- and biocatalyzed transformations as well as to the synthesis of Active Pharmaceutical Ingredients (APIs) and other biologically relevant compounds by providing, through discussion of all relevant literature over the past five years, a comparison of the outcomes of the reactions when carried out in one or the other solvent.
Organolithium compounds have been at the forefront of synthetic chemistry for over a century, as they mediate the synthesis of myriads of compounds that are utilised worldwide in academic and industrial settings. For that reason, lithium has always been the most important alkali metal in organometallic chemistry. Today, that importance is being seriously challenged by sodium and potassium, as the alkali-metal mediation of organic reactions in general has started branching off in several new dire...
Abstract An efficient protocol was developed for the synthesis of tertiary alcohols via nucleophilic addition of organometallic compounds of s-block elements (Grignard and organolithium reagents) to esters performed in the biodegradable choline chloride/urea eutectic mixture or in water. This approach displays a broad substrate scope, with the addition reaction proceeding quickly (20 s reaction time) and cleanly, at ambient temperature and under air, straightforwardly furnishing the expected ter...
Last. Joshua Sangoro(UT: University of Tennessee)H-Index: 27
view all 19 authors...
Deep eutectic solvents (DESs) are an emerging class of mixtures characterized by significant depressions in melting points compared to those of the neat constituent components. These materials are promising for applications as inexpensive "designer" solvents exhibiting a host of tunable physicochemical properties. A detailed review of the current literature reveals the lack of predictive understanding of the microscopic mechanisms that govern the structure-property relationships in this class of...
#2Deng-En Hua(Zhejiang University of Technology)H-Index: 2
Last. Yu-Guo Zheng(Zhejiang University of Technology)H-Index: 29
view all 6 authors...
Abstract The whole-cell nitrilase-catalyzed asymmetric hydrolysis of nitriles is a green and efficient preparation approach for chiral carboxylic acids, but often suffers from toxicity and cell lysis from organic substrates. In this work, a novel integrated process for whole-cell nitrilase-catalyzed asymmetric hydrolysis was developed for the first time by introducing a biocompatible ionic liquid (IL)-based biphasic system. The whole-cell nitrilases displayed an outstanding stability and recycla...
#2Frank Hollmann(TU Delft: Delft University of Technology)H-Index: 60
Abstract Following ionic liquids, (natural) deep eutectic solvents ((NA)DES) are receiving significant attention as performance additives for biocatalytic reactions. (NA)DES are increasingly evaluated as solvents to replace water in hydrolase-catalyzed esterification reactions thereby shifting the reaction equilibrium. They also frequently outperform water in terms of solubility properties of hydrophobic reagents and thereby enable higher space-time yields. Furthermore, (NA)DES frequently exceed...
#1Shuhong Mao(Tianjin University of Science and Technology)H-Index: 8
#2Xiaorui Wang(Tianjin University of Science and Technology)H-Index: 2
Last. Hui-Min Qin(Tianjin University of Science and Technology)H-Index: 11
view all 7 authors...
Abstract Penicillium raistrickii-mediated 15α-hydroxylation of D-ethylgonendione is a key step for industrial production of gestodene. However, the process efficiency is limited due to the poor solubility of the steroid in aqueous water system. Deep eutectic solvents (DESs) are promising solvents applied widely in biocatalysis. Here we systematically investigated the biotransformation performance of P.raistrickii in 14 different DESs containing system. DESs with different HBD exhibited different...
The Meyer-Schuster rearrangement of propargylic alcohols into α,β-unsaturated carbonyl compounds has been revisited by setting up an atom-economic process catalyzed by a deep eutectic solvent FeCl3·6H2O/glycerol. Isomerizations take place smoothly, at room temperature, under air and with short reaction times. The unique solubilizing properties of the eutectic mixture enabled the use of a substrate concentration up to 1.0 M with the medium being recycled up to ten runs without any loss of catalyt...
Last. Marcos R. Mafra(UFPR: Federal University of Paraná)H-Index: 16
view all 6 authors...
Abstract The knowledge about the solubility behavior of different biomolecules can be of interest to the pharmaceutical, chemical, and food industries. In this work, the designer solvents were evaluated as additives to aqueous media to enhance the solubility of hydrophobic biomolecules, namely: quercetin, curcumin, and gallic acid. The solubilities of these biomolecules were explored in terms of experimental data and COSMO-based models' prediction (COSMO-RS and COSMO-SAC). The following designer...
Core tools of synthetic chemistry, polar organometallic reagents (typified by organolithium and Grignard reagents) are used worldwide for constructing compounds, especially aromatic compounds, which are ubiquitous in organic chemistry and thus in numerous commodities essential to everyday life. By isolation and characterisation of key organometallic intermediates, research in our group has led to the design of polar mixed-metal reagents imbued with synergistic effects that display chemical prope...
This work was supported by the University of Alicante (VIGROB-316FI and VIGORB20-170) and the Spanish Ministerio de Economia, Industria y Competitividad (PGC2018-096616-B-100). NGG and BS thank Generalitat Valenciana (ACIF/2020/186 and ACIF/2017/211, respectively) for their fellowships.
Abstract null null The use of deep eutectic solvents (DES) with buffer as cosolvent (up to 10 % v/v) leads to low-viscous media in which lipases can perform synthetic reactions, instead of hydrolysis. This paper explores the immobilization of Pseudomonas stutzeri lipase (TL) in cross-linking aggregates (CLEA) to deliver robust derivatives that are active in media like choline chloride – glycerol DES with buffer as cosolvent. While the free TL enzyme was markedly inactive in these media, TL-CLEA ...
Last. Pu Wang(Zhejiang University of Technology)H-Index: 6
view all 0 authors...
(R)-1-[3-(Trifluoromethyl)phenyl]ethanol ((R)-MTF-PEL) is an important chiral building block for the synthesis of a neuroprotective compound, (R)-3-(1-(3-(trifluoromethyl)phenyl)ethoxy)azetidine-1-carboxamide. In this work, an effective whole-cell-catalyzed biotransformation was developed to produce (R)-MTF-PEL, and its productivity was increased by medium engineering strategy. The recombinant E. coli BL21(DE3)-pET28a(+)-LXCAR-S154Y variant affording carbonyl reductase was adopted for the reduct...
Alkoxide-mediated enolization of 1-arylpropan-2-ones and their fluorinated derivatives, followed by α-functionalization with nucleophilic addition and substitution reactions, has been accomplished in the environmentally friendly eutectic mixture choline chloride/urea, under aerobic conditions. The usefulness of this new protocol has also been exemplified through the synthesis of a small selection of building-block like molecules through Pd-catalyzed α-arylation reactions.
Abstract Recently, there has been an upsurge interest in developing chemoselective and fast processes when working with polar organometallic of s- and d-block elements and alkali-metal reagents under air and moisture, and also in protic bio-based solvents like Deep Eutectic Solvents or water. A discussion is offered highlighting cutting-edge stoichiometric and catalytic synthetic applications in this evolving field, with an accent over the literature published in the last couple of years.
The identification of a green, versatile, user-friendly and efficient methodology is necessary to facilitate the use of Heck-Cassar-Sonogashira (HCS) cross coupling reaction in drug discovery and industrial production in the pharmaceutical segment. The Heck-Cassar and Sonogashira protocols, using HEP/water/TMG as green solvents/base mixture, and sulfonated phosphine ligands allow to recycle the catalysts, always guaranteeing high yields and fast conversions under mild conditions, with aryl iodid...
