{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T20:26:20Z","timestamp":1773519980248,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","doi-asserted-by":"publisher","award":["UIDB\/50006\/2020|UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020|UIDP\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","doi-asserted-by":"publisher","award":["UIDB\/00313\/2020|UIDP\/00313\/2020"],"award-info":[{"award-number":["UIDB\/00313\/2020|UIDP\/00313\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Catalysts"],"abstract":"<jats:p>Deep eutectic solvents (DESs) are a mixture of two or more components, and at a particular composition, they become liquids at room temperature. When the compounds that constitute the DESs are primary metabolites namely, amino acids, organic acids, sugars, or choline derivatives, the DESs are called natural deep eutectic solvents (NADESs). NADESs fully represent green chemistry principles. These solvents are highly welcome, as they are obtained from renewable resources, and gratifyingly are biodegradable and biocompatible. They are an alternative to room-temperature ionic liquids (RTILs). From the pharmaceutical industry\u2019s point of view, they are highly desirable, but they unfortunately have been rarely used despite their enormous potential. In this review, we look at their impact on the asymmetric catalytic synthesis of key target molecules via metal-based catalysis, biocatalysis, and organocatalysis. In many cases, the NADESs that have been used are chiral and can even promote enantioselective reactions; this crucial and very exciting aspect is also discussed and analyzed.<\/jats:p>","DOI":"10.3390\/catal14030160","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T11:35:04Z","timestamp":1708515304000},"page":"160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Stereoselective Catalytic Synthesis of Bioactive Compounds in Natural Deep Eutectic Solvents (NADESs): A Survey across the Catalytic Spectrum"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8117-7737","authenticated-orcid":false,"given":"Elisabete P.","family":"Carreiro","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Institute for Research and Advanced Studies, University of \u00c9vora, Rua Rom\u00e3o Ramalho 59, 7000-671 \u00c9vora, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-1689","authenticated-orcid":false,"given":"Hans-J\u00fcrgen","family":"Federsel","sequence":"additional","affiliation":[{"name":"ChiraTecnics, Apartado 10065, 3031-601 Coimbra, Portugal"},{"name":"Laboratory 010, School of Sciences and Technology, Phase III, University of \u00c9vora, Rua Rom\u00e3o Ramalho 59, 7000-671 \u00c9vora, Portugal"},{"name":"RISE Research Institutes of Sweden, P.O. Box 5607, SE-114 86 Stockholm, Sweden"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5726-4881","authenticated-orcid":false,"given":"Gesine J.","family":"Hermann","sequence":"additional","affiliation":[{"name":"ChiraTecnics, Apartado 10065, 3031-601 Coimbra, Portugal"},{"name":"Laboratory 010, School of Sciences and Technology, Phase III, University of \u00c9vora, Rua Rom\u00e3o Ramalho 59, 7000-671 \u00c9vora, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-1116","authenticated-orcid":false,"given":"Anthony J.","family":"Burke","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Institute for Research and Advanced Studies, University of \u00c9vora, Rua Rom\u00e3o Ramalho 59, 7000-671 \u00c9vora, Portugal"},{"name":"Faculty Pharmacy, University of Coimbra, P\u00f3lo das Ci\u00eancias da Sa\u00fade, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"Centro de Qu\u00edmica de Coimbra, Institute of Molecular Sciences (CQC-IMS), Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade de Coimbra, 3004-535 Coimbra, Portugal"},{"name":"Center for Neurosciences and Cellular Biology (CNC), Faculdade de Medicina da Universidade de Coimbra, Polo I, 1\u00baandar, 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Francotte, E., and Lindner, W. (2006). Chiral Drugs from a Historical Point of View in Chirality in Drug Research, Wiley-VCH.","DOI":"10.1002\/3527609431"},{"key":"ref_2","unstructured":"Francotte, E., and Lindner, W. (2006). Stereoselective Synthesis of Drugs\u2013An Industrial Perspective in Chirality in Drug Research, Wiley-VCH."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Burke, A.J., Marques, C.S., Turner, N.J., and Hermann, G.J. (2018). Active Pharmaceutical Ingredients in Synthesis\u2013Catalytic Processes in Research and Development, Wiley-VCH.","DOI":"10.1002\/9783527807253"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"De Vos, D.E., Vankelecom, I.F.J., and Jacobs, P.A. (2000). Enantioselective Heterogenous Catalysis: Academic and Industrial Challenges in Chiral Catalyst Immobilization and Recycling, Wiley-VCH.","DOI":"10.1002\/9783527613144"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wasserscheid, P., and Welton, T. (2003). Ionic Liquids in Synthesis, Wiley-VCH.","DOI":"10.1002\/3527600701"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1126\/science.266.5182.72","article-title":"Facil catalyst separation without water: Fluorous biphase hydroformylation of olefins","volume":"266","year":"1994","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1039\/b106357j","article-title":"Preparation of novel, moisture-stable, Lewis-acidic ionic liquids containing quaternary ammonium salts with functional side chains","volume":"19","author":"Abbott","year":"2001","journal-title":"Chem. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4065","DOI":"10.1002\/ejoc.202100385","article-title":"Asymmetric Organocatalysis in Deep Eutectic Solvents","volume":"29","author":"Alonso","year":"2021","journal-title":"Eur. J. Org. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"131967","DOI":"10.1016\/j.tet.2021.131967","article-title":"Organocatalytic transformations in deep eutectic solvents: Green methodologies made greener","volume":"84","author":"Amo","year":"2021","journal-title":"Tetrahedron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/cctc.201501133","article-title":"Deep eutectic solventes for organocatalysis, biotransformations, and multistep organocatalyst\/enzyme combinations","volume":"8","author":"Guajardo","year":"2016","journal-title":"ChemCatChem"},{"key":"ref_11","first-page":"1232","article-title":"Deep Eutectic Solvents: A Review of Fundamentals and Applications","volume":"3","author":"Hansen","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1021\/sc500096j","article-title":"Natural Deep Eutectic Solvents\u2212Solvents for the 21st Century","volume":"5","author":"Paiva","year":"2014","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1080\/17460441.2023.2160437","article-title":"Update on Asymmetric Organocatalytic Approaches for Accessing Drugs","volume":"18","author":"Burke","year":"2023","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1039\/C5GC02526E","article-title":"Bio-renewable enantioselective aldol reaction in natural deep eutectic solvents","volume":"18","author":"Berbegal","year":"2016","journal-title":"Green Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.tetasy.2016.12.009","article-title":"Organocatalytic enantioselective conjugate addition of aldehydes to maleimides in deep eutectic solvents","volume":"28","author":"Chinchilla","year":"2017","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"\u00d1\u00edguez, D.R., Khazaeli, P., Alonso, D.A., and Guillen, G. (2018). Deep Eutectic Mixtures as Reaction Media for the Enantioselective Organocatalyzed \u03b1-Amination of 1,3-Dicarbonyl Compounds. Catalysts, 8.","DOI":"10.3390\/catal8050217"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1055\/a-1916-4858","article-title":"Immobilization of Functionalized epi-Cinchonine Organocatalysts on Controlled Porous Glass-Beads: Applications in Batch and Continuous Flow","volume":"33","author":"Amorim","year":"2022","journal-title":"Synlett"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1055\/a-2117-9971","article-title":"Sustainable OrganoCatalyzed Enantioselective Catalytic Michael Additions in Betaine derived Deep Eutectic Solvents","volume":"7","author":"Amorim","year":"2023","journal-title":"SynOpen"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113573","DOI":"10.1016\/j.molliq.2020.113573","article-title":"L-Proline-based deep eutectic solvents based on their structural features","volume":"313","author":"Tiecco","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.2174\/1385272827666230214091448","article-title":"Discovery of Deep Eutectic Solvents in Organic Synthesis: An insight into their current applications and prospect","volume":"26","author":"Tang","year":"2022","journal-title":"Curr. Org. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6555","DOI":"10.1039\/D1GC01647D","article-title":"Natural eutectogels: Sustainable catalytic systems for C-C bond formation reactions","volume":"23","author":"Saavedra","year":"2021","journal-title":"Green Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1073\/pnas.82.10.3192","article-title":"Enzyme-catalyzed processes in organic solvents","volume":"82","author":"Zaks","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/35051719","article-title":"Improving enzymes by using them in organic solvents","volume":"409","author":"Klibanov","year":"2001","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.tibtech.2019.03.007","article-title":"Deep Eutectic Solvents as Efficient Solvents in Biocatalysis","volume":"37","author":"Siebenhaller","year":"2019","journal-title":"Trends Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1039\/b716317g","article-title":"Hydrolase-catalyzed biotransformations in deep eutectic solvents","volume":"10","author":"Gorke","year":"2008","journal-title":"Chem. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/ejlt.201400459","article-title":"Lipase-catalyzed synthesis of glucose-6-O-hexanoate in deep eutectic solvents","volume":"117","author":"Ulrich","year":"2015","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hollenbach, R., Bindereif, B., Van der Schaaf, U.S., Ochsenreither, K., and Syldatk, C. (2020). Optimization of glycolipid synthesis in hydrophilic deep eutectic solvents. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00382"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hollenbach, R., Ochsenreither, K., and Syldatk, C. (2020). Enzymatic synthesis of glucose monodecanoate in a hydrophobic deep eutectic solvent. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124342"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5926","DOI":"10.1021\/acssuschemeng.2c07607","article-title":"Deep Eutectic Solvents for the Enzymatic Synthesis of Sugar Esters: A Generalizable Strategy?","volume":"11","author":"Semproli","year":"2023","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.mcat.2019.01.012","article-title":"Comparison of deep eutectic solvents and solvent-free reaction conditions for aldol production","volume":"466","author":"Milker","year":"2019","journal-title":"Mol. Catal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4014\/jmb.1506.06075","article-title":"Enzyme-Catalyzed Henry Reaction in Choline Chloride-Based Deep Eutectic Solvents","volume":"26","author":"Tian","year":"2016","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.molcatb.2014.06.003","article-title":"Benzaldehyde lyase (BAL)-catalyzed enantioselective C-C bond formation in deep-eutectic-solvents\u2013buffer mixtures","volume":"107","author":"Maugeri","year":"2017","journal-title":"J. Mol. Catal. B Enzym."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1128\/JVI.77.9.5201-5208.2003","article-title":"Analysis of the mechanism by which the small-Molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus type 1 entry","volume":"77","author":"Tsamis","year":"2003","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1007\/s00449-020-02387-5","article-title":"Development of biocompatible DES\/NADES as co-solvents for efficient biosynthesis of chiral alcohols","volume":"43","author":"Xia","year":"2020","journal-title":"Bioprocess Biosyst. Eng."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"He, Y., Huang, Q., and Wang, P. (2020). Design and evaluation of novel bio-based deep eutectic solvents for highly efficient bioproduction of chiral aryl alcohol. J. Chem. Technol. Biotechnol., 95.","DOI":"10.1002\/jctb.6386"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"234","DOI":"10.21037\/atm.2019.12.158","article-title":"Fosaprepitant versus aprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: A multicenter, randomized, double-blind, double-simulated, positive-controlled phase III trial","volume":"8","author":"Zhang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhu, Z., Bi, S., Ye, N., and Wang, P. (2020). High-Efficient Production of (S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol via Whole-Cell Catalyst in Deep-Eutectic Solvent-Containing Micro-Aerobic Medium System. Molecules, 25.","DOI":"10.3390\/molecules25081855"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.1021\/cr040700c","article-title":"Asymmetric Synthesis of Active Pharmaceutical Ingredients","volume":"106","author":"Farina","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Marset, X., and Guillena, G. (2022). Deep Eutectic Solvents as \u00e0-la-Carte Medium for Transition-Metal-Catalyzed Organic Processes. Molecules, 27.","DOI":"10.3390\/molecules27238445"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/j.cclet.2019.05.063","article-title":"DESs: Green solvents for transition metal catalyzed organic reactions","volume":"30","author":"Peng","year":"2019","journal-title":"Chin. Chem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1039\/D0OB02491K","article-title":"Advances in deep eutectic solvents and water: Applications in metal- and biocatalyzed processes, in the synthesis of APIs, and other biologically active compounds","volume":"19","author":"Cicco","year":"2021","journal-title":"Org. Biomol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18630","DOI":"10.1021\/acssuschemeng.9b05073","article-title":"One-Pot Diastereoselective Synthesis of Tetrahydroquinolines from Star Anise Oil in a Choline Chloride\/Zinc Chloride Eutectic Mixture","volume":"7","author":"Kouznetsov","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26189","DOI":"10.1039\/D3RA05561B","article-title":"Diastereoselective multicomponent synthesis of dihydroisoindolo [2,1-a]quinolin-11-ones mediated by eutectic solvents","volume":"13","author":"Kouznetsov","year":"2023","journal-title":"RSC Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e6418","DOI":"10.1002\/aoc.6418","article-title":"Indium-mediated allylation of carbonyl compounds in deep eutectic solvents","volume":"35","author":"Saavedra","year":"2021","journal-title":"Appl. Organomet. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e202217713","DOI":"10.1002\/anie.202217713","article-title":"Chemoenzymatic Cascades Combining Biocatalysis and Transition Metal Catalysis for Asymmetric Synthesis","volume":"62","author":"Escot","year":"2023","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1039\/C8GC00861B","article-title":"Programming Cascade Reactions Interfacing Biocatalysis with Transition-Metal Catalysis in Deep Eutectic Solvents as Biorenewable Reaction Media","volume":"20","author":"Cicco","year":"2018","journal-title":"Green Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1002\/cctc.201800768","article-title":"Novel insights into the combination of metal- and biocatalysis: Cascade one-pot synthesis of enantiomerically pure biaryl alcohols in deep eutectic solvents","volume":"10","author":"Paris","year":"2018","journal-title":"ChemCatChem"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1021\/acssuschemeng.8b06715","article-title":"Enantioselective One-Pot Synthesis of Biaryl-Substituted Amines by Combining Palladium and Enzyme Catalysis in Deep Eutectic Solvents","volume":"7","author":"Paris","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.micromeso.2016.11.009","article-title":"Deep eutectic solvent immobilized on SBA-15 as a novel separable catalyst for one-pot three-component Mannich reaction","volume":"240","author":"Azizi","year":"2017","journal-title":"Microporous Mesoporous Mater."}],"container-title":["Catalysts"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4344\/14\/3\/160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:02:42Z","timestamp":1760104962000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4344\/14\/3\/160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,21]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["catal14030160"],"URL":"https:\/\/doi.org\/10.3390\/catal14030160","relation":{},"ISSN":["2073-4344"],"issn-type":[{"value":"2073-4344","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,21]]}}}