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Catalytic Procedures for the Synthesis of Pharmaceutical Active Compounds in...
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Catalytic Procedures for the Synthesis of Pharmaceutical Active Compounds in Deep Eutectic Solvents

A special issue of Catalysts (ISSN 2073-4344). This special issue belongs to the section "Catalysis for Pharmaceuticals".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 18073

Special Issue Editors

Prof. Dr. Andres R. Alcantara

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Guest Editor
Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Complutense University, Plaza De Ramon y Cajal, S/N University City, Madrid, Spain
Interests: enzymatic synthesis of drugs and bioactive compounds; sustainable processes; biocatalyst upgrading; pharmaceutical industry; organic chemistry; pharmaceutical chemistry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Gonzalo de Gonzalo

E-Mail Website
Guest Editor
Departamento de Química Orgánica, Universidad de Sevilla, 41014 Sevilla, Spain
Interests: biocatalysis; catalytic reactions; sustainable chemistry; pharmaceutical synthesis; deep eutectic solvents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The solvent in which catalyzed reactions are performed constitutes the main proportion of the chemicals employed, with it being the reaction medium and employed in purification/extraction protocols. In recent years, the need for more sustainable processes while maintaining the efficiency and selectivity of the reactions, has made the search for novel green solvents an area of overwhelming interest. In line with this, Deep Eutectic Solvents (DESs), liquid compounds formed by the combination of a hydrogen bond-donor with a hydrogen-bond acceptor at equimolecular quantities, have appeared as an interesting alternative to the classical solvents. DESs are generally obtained from renewable sources, are easy to prepare with complete atom efficiency, and are non-toxic and biodegradable, while presenting a wide range of physical-chemical properties. For these reasons, their application as reaction (co)solvents has grown in recent years. In this Special Issue, the latest developments for the preparation of pharmaceutical compounds in catalytic processes employing DESs will be shown.

Prof. Dr. Andres R. Alcantara
Prof. Dr. Gonzalo de Gonzalo
Guest Editors

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Keywords

  • green chemistry
  • catalysis
  • pharmaceutical chemistry
  • deep eutectic solvents drugs/biomass-derived solvents

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Published Papers (5 papers)

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Research

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20 pages, 4626 KiB  
Article
Enzymatic Oxidation of Hydroxytyrosol in Deep Eutectic Solvents for Chitosan Functionalization and Preparation of Bioactive Nanogels
by Myrto G. Bellou, Anastasia Skonta, Alexandra V. Chatzikonstantinou, Angeliki C. Polydera, Petros Katapodis, Epaminondas Voutsas and Haralambos Stamatis
Catalysts 2025, 15(2), 180; https://doi.org/10.3390/catal15020180 - 14 Feb 2025
Viewed by 520
Abstract
Biocatalytic processes for the formation of bioactive compounds and biopolymer preparations that can be applied in pharmaceuticals and cosmetics are gaining increasing interest due to their safety and sustainability, relying on environmentally friendly approaches and biocompatible compounds. In this work, we investigate the [...] Read more.
Biocatalytic processes for the formation of bioactive compounds and biopolymer preparations that can be applied in pharmaceuticals and cosmetics are gaining increasing interest due to their safety and sustainability, relying on environmentally friendly approaches and biocompatible compounds. In this work, we investigate the implementation of various Deep Eutectic Solvents (DES) in the laccase-catalyzed oxidation of hydroxytyrosol (HT), aiming to produce its oligomer derivatives such as HT dimer and trimer. The composition of the reaction mixture in which the oligomers’ yield was the highest was 70% v/v Bet:PG (1:4 molar ratio). The oligomers formed were subsequently used for the non-enzymatic grafting of chitosan (CS) and the development of bioactive chitosan-based nanogels (NG). Grafted chitosan nanogels were prepared by ionic gelation using sodium tripolyphosphate (TPP) as a cross-linking agent. The functionalized chitosan was characterized using Fourier-Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy, while Scanning Electron Microscopy (SEM) was employed for nanogel characterization. Compared to unmodified chitosan nanogels, grafted chitosan nanogels exhibited almost ten-fold higher antioxidant activity and approximately 20% greater antibacterial activity. Full article
(This article belongs to the Special Issue Catalytic Procedures for the Synthesis of Pharmaceutical Active Compounds in Deep Eutectic Solvents)
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Review

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24 pages, 2031 KiB  
Review
Strategies to Prepare Chitin and Chitosan-Based Bioactive Structures Aided by Deep Eutectic Solvents: A Review
by D. Alonzo Durante-Salmerón, Isabel Fraile-Gutiérrez, Rubén Gil-Gonzalo, Niuris Acosta, Inmaculada Aranaz and Andrés R. Alcántara
Catalysts 2024, 14(6), 371; https://doi.org/10.3390/catal14060371 - 10 Jun 2024
Cited by 2 | Viewed by 3215
Abstract
Chitin and chitosan, abundant biopolymers derived from the shells of crustaceans and the cell walls of fungi, have garnered considerable attention in pharmaceutical circles due to their biocompatibility, biodegradability, and versatile properties. Deep eutectic solvents (DESs), emerging green solvents composed of eutectic mixtures [...] Read more.
Chitin and chitosan, abundant biopolymers derived from the shells of crustaceans and the cell walls of fungi, have garnered considerable attention in pharmaceutical circles due to their biocompatibility, biodegradability, and versatile properties. Deep eutectic solvents (DESs), emerging green solvents composed of eutectic mixtures of hydrogen bond acceptors and donors, offer promising avenues for enhancing the solubility and functionality of chitin and chitosan in pharmaceutical formulations. This review delves into the potential of utilizing DESs as solvents for chitin and chitosan, highlighting their efficiency in dissolving these polymers, which facilitates the production of novel drug delivery systems, wound dressings, tissue engineering scaffolds, and antimicrobial agents. The distinctive physicochemical properties of DESs, including low toxicity, low volatility, and adaptable solvation power, enable the customization of chitin and chitosan-based materials to meet specific pharmaceutical requirements. Moreover, the environmentally friendly nature of DESs aligns with the growing demand for sustainable and eco-friendly processes in pharmaceutical manufacturing. This revision underscores recent advances illustrating the promising role of DESs in evolving the pharmaceutical applications of chitin and chitosan, laying the groundwork for the development of innovative drug delivery systems and biomedical materials with enhanced efficacy and safety profiles. Full article
(This article belongs to the Special Issue Catalytic Procedures for the Synthesis of Pharmaceutical Active Compounds in Deep Eutectic Solvents)
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16 pages, 2706 KiB  
Review
Stereoselective Catalytic Synthesis of Bioactive Compounds in Natural Deep Eutectic Solvents (NADESs): A Survey across the Catalytic Spectrum
by Elisabete P. Carreiro, Hans-Jürgen Federsel, Gesine J. Hermann and Anthony J. Burke
Catalysts 2024, 14(3), 160; https://doi.org/10.3390/catal14030160 - 21 Feb 2024
Cited by 4 | Viewed by 2418
Abstract
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 [...] Read more.
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’s 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. Full article
(This article belongs to the Special Issue Catalytic Procedures for the Synthesis of Pharmaceutical Active Compounds in Deep Eutectic Solvents)
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16 pages, 3614 KiB  
Review
Deep Eutectic Solvents as Catalysts in the Synthesis of Active Pharmaceutical Ingredients and Precursors
by Chiara Falcini and Gonzalo de Gonzalo
Catalysts 2024, 14(2), 120; https://doi.org/10.3390/catal14020120 - 2 Feb 2024
Cited by 8 | Viewed by 3687
Abstract
Deep Eutectic Solvents (DESs) have appeared in recent years as an appealing alternative to classical organic solvents, due to their valuable environmental properties. In addition, these compounds, formed by the combination of one hydrogen bond donor with a hydrogen bond acceptor at a [...] Read more.
Deep Eutectic Solvents (DESs) have appeared in recent years as an appealing alternative to classical organic solvents, due to their valuable environmental properties. In addition, these compounds, formed by the combination of one hydrogen bond donor with a hydrogen bond acceptor at a defined stoichiometric ratio, present other valuable activities not only as a reaction medium. DESs can also be employed as catalysts through hydrogen-bond interactions in different chemical transformations, thus substituting hazardous reagents and solvents. The search for novel and more environmentally friendly catalysts is an area of interest of pharmaceutical chemists, and therefore, the efforts made in the application of DESs as catalysts in the synthesis of APIs or its precursors are described, focusing mainly on condensations, nucleophilic additions to carbonyl moieties, and multicomponent reactions. Full article
(This article belongs to the Special Issue Catalytic Procedures for the Synthesis of Pharmaceutical Active Compounds in Deep Eutectic Solvents)
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29 pages, 9554 KiB  
Review
Biocatalysis for the Synthesis of Active Pharmaceutical Ingredients in Deep Eutectic Solvents: State-of-the-Art and Prospects
by Ningning Zhang, Pablo Domínguez de María and Selin Kara
Catalysts 2024, 14(1), 84; https://doi.org/10.3390/catal14010084 - 19 Jan 2024
Cited by 25 | Viewed by 7083
Abstract
Biocatalysis holds immense potential for pharmaceutical development as it enables synthetic routes to various chiral building blocks with unparalleled selectivity. Therein, solvent and water use account for a large contribution to the environmental impact of the reactions. In the spirit of Green Chemistry [...] Read more.
Biocatalysis holds immense potential for pharmaceutical development as it enables synthetic routes to various chiral building blocks with unparalleled selectivity. Therein, solvent and water use account for a large contribution to the environmental impact of the reactions. In the spirit of Green Chemistry, a transition from traditional highly diluted aqueous systems to intensified non-aqueous media to overcome limitations (e.g., water shortages, recalcitrant wastewater treatments, and low substrate loadings) has been observed. Benefiting from the spectacular advances in various enzyme stabilization techniques, a plethora of biotransformations in non-conventional media have been established. Deep eutectic solvents (DESs) emerge as a sort of (potentially) greener non-aqueous medium with increasing use in biocatalysis. This review discusses the state-of-the-art of biotransformations in DESs with a focus on biocatalytic pathways for the synthesis of active pharmaceutical ingredients (APIs). Representative examples of different enzyme classes are discussed, together with a critical vision of the limitations and discussing prospects of using DESs for biocatalysis. Full article
(This article belongs to the Special Issue Catalytic Procedures for the Synthesis of Pharmaceutical Active Compounds in Deep Eutectic Solvents)
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