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| 2. |
- Burke, Anthony, et al.
(författare)
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Immobilization of Functionalized epi-Cinchonine Organocatalysts on Controlled Porous Glass-Beads : Applications in Batch and Continuous Flow
- 2022
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Ingår i: Synlett. - : Georg Thieme Verlag. - 0936-5214 .- 1437-2096. ; 33:17, s. 1756-1762
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Tidskriftsartikel (refereegranskat)abstract
- A well-known Squaramide-Cinchonine organocatalyst was immobilized in a controlled way onto three types of commercial porous glass beads EziGTM (EziG OPAL, EziG Amber and EziG Coral) and applied in asymmetric Michael reactions. The performance of the immobilized catalysts was evaluated under batch and continuous flow conditions showing promising results in both approaches. In batch reactions, 0.8 and 1.6 mol% of the immobilized cinchonine-squaramide provided the products with excellent yields (up to 99%) and enantioselectivities (up to 99% ee). These excellent results were also verified in the case of continuous flow reactions, where also 0.8 and 1.6 mol% of the catalyst immobilized onto the glass beads afforded the product with extraordinary yields (up to 99%) and very high enantioselectivities (up to 97% ee). The immobilized catalysts could be recycled (up to 7 cycles) using both approaches.
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| 3. |
- Burke, Anthony, et al.
(författare)
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Recent Advances in Asymmetric Hydrogenation Catalysis Utilizing Spiro and Other Rigid C-Stereogenic Phosphine Ligands
- 2022
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society. - 0022-3263 .- 1520-6904. ; 87:4, s. 1898-1924
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Tidskriftsartikel (refereegranskat)abstract
- Transition-metal-catalyzed asymmetric reactions have been a powerful tool in organic synthesis for many years. The design of chiral ligands with the right configuration is fundamental to induce high regio- and stereoselectivity to catalytic reactions and to achieve high turnover numbers and high yields. A challenge is the control of prochiral centers with similar electronic properties in a similar steric environment within the same molecule. Over the last 10 years, a range of novel rigid C-stereogenic chiral phosphine ligands has been developed and successfully applied in various types of asymmetric transformations. Many of these ligands are of a di-, tri-, or multidentate nature. The purpose of this Perspective is to highlight recent synthetic achievements (since 2010) with spiro-phosphines and other rigid phosphines and discuss some mechanistic aspects of the catalytic reactions.
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| 4. |
- Carreiro, Elisabete P., et al.
(författare)
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Asymmetric Additions Empowered by OrganoCatalysts, Metal Catalysts, and Deep Natural Eutectic Solvents (NADES)
- 2024
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society. - 0022-3263 .- 1520-6904. ; 89, s. 6631-
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Tidskriftsartikel (refereegranskat)abstract
- This article is a history of an industrial-academic partnership that started almost two decades ago and details the evolution of a relationship between a small academic research group and a spin-out company located in Portugal. Their activities have ranged from the development of new metal-based catalytic systems for asymmetric epoxidations, allylic alkylations, and arylations to the development of novel cinchona-based organocatalysts for asymmetric hydrosilylations and Michael additions. Current common interests are centered on the development of novel chiral Natural Deep Eutectic Solvent systems, which they are investigating in different types of reaction systems.
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| 5. |
- Carreiro, Elisabete P., et al.
(författare)
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Stereoselective Catalytic Synthesis of Bioactive Compounds in Natural Deep Eutectic Solvents (NADESs) : A Survey across the Catalytic Spectrum
- 2024
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Ingår i: Catalysts. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2073-4344. ; 14:3
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Tidskriftsartikel (refereegranskat)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 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. © 2024 by the authors.
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| 6. |
- Federsel, Hans-Jürgen, et al.
(författare)
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C-N Coupling Chemistry as a Means to Achieve a Complicated Molecular Architecture : the AR-A2 Case Story
- 2013
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Ingår i: Transition Metal-Catalyzed Couplings in Process Chemistry. - Weinheim, Germany : Wiley-VCH Verlag. - 9783527658909 - 9783527332793 ; , s. 73-89
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- A major drug project in the neuroscience area aimed at designing and developing a viable manufacturing process for AR-A2. This turned out to be a tough challenge that resulted in the use of three different synthetic routes. One step to be included from the very start was a Pd-catalyzed C-N bond formation, and this was retained throughout the later versions of the synthesis. At the time of initiating this project in 1998, the combined Buchwald and Hartwig protocols for effecting the chemistry in question-coupling of a N-containing moiety to an aromatic nucleus had only been known for a few years. Therefore, a lot of experimentation was needed to increase the insight and understanding of the chemistry to optimize the performance to fit for large-scale application. The outcome of the efforts resulted in successfully carrying out the chemical transformation is described in detail in this chapter.
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| 7. |
- Federsel, Hans-Jürgen, et al.
(författare)
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Recent trends in enzyme immobilization—concepts for expanding the biocatalysis toolbox
- 2021
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 26:9
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Tidskriftsartikel (refereegranskat)abstract
- Enzymes have been exploited by humans for thousands of years in brewing and baking, but it is only recently that biocatalysis has become a mainstream technology for synthesis. Today, enzymes are used extensively in the manufacturing of pharmaceuticals, food, fine chemicals, flavors, fragrances and other products. Enzyme immobilization technology has also developed in parallel as a means of increasing enzyme performance and reducing process costs. The aim of this review is to present and discuss some of the more recent promising technical developments in enzyme immobilization, including the supports used, methods of fabrication, and their application in synthesis. The review highlights new support technologies such as the use of well-established polysaccharides in novel ways, the use of magnetic particles, DNA, renewable materials and hybrid organic–inorganic supports. The review also addresses how immobilization is being integrated into developing biocatalytic technology, for example in flow biocatalysis, the use of 3D printing and multi-enzymatic cascade reactions. © 2021 by the authors.
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| 8. |
- Federsel, Hans-Jürgen
(författare)
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Taking the Green Road Towards Pharmaceutical Manufacturing
- 2022
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Ingår i: Synthesis (Stuttgart). - : Georg Thieme Verlag. - 0039-7881 .- 1437-210X. ; 54:19, s. 4257-
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of the Green Chemistry Principles in the late 1990s formed the basis for a transition to a greener environment. These Principles have become an integral part in the work on designing chemical processes, especially for large-scale manufacture. The ultimate target is the achievement of a sustainable production method allowing hundreds of tons of valuable materials to be prepared. For this purpose, a holistic view must be applied to the elements constituting a fullyfledged process encompassing layout of the synthetic route, defining starting materials and their origin, output of product and quality features, quantity of effluent streams and waste, recovery and recycling of chemicals involved, and energy consumption. These parameters form a complex matrix where the individual components are in a complicated relationshipwith each other. This short review addresses these issues and the benefits of life-cycle assessment and metrics commonly used to measure the performance of chemical manufacturing all from a pharmaceutical industry perspective as experienced by the author.
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| 9. |
- Federsel, Hans-Jürgen
(författare)
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What enables and blocks synthetic chemistry methods in becoming industrially significant?
- 2023
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Ingår i: Cell Reports Physical Science. - : Cell Press. - 2666-3864. ; 4:7
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Forskningsöversikt (refereegranskat)abstract
- What factors will play a role in the decision process when looking at the reasons for certain reactions being adopted for large-scale industrial applications? An examination reveals that there are several parameters that have the power to be influential in this regard, either on their own or in combination, all dependent on the circumstances. Seen from a pharmaceutical manufacturing point of view, only certain structural motifs are of interest for in-depth investigations and, hence, are in demand of synthetic methodologies allowing the preparation of quantities beyond what sensibly is achieved by ordinary laboratory procedures. This inevitably leads to many reactions and even reaction types to fall by the wayside. A further criterion to fulfill is that a given synthesis must perform in a robust and consistent manner, irrespective of scale. Many methods used in the laboratory are demanding but can be handled and controlled by scientists well-versed in the art of organic synthesis. On scale-up, such reactions could behave in a capricious way, for example under the influence of issues with heat transfer and stirring efficiency, sensitivity to trace amounts of water, or being exposed to a non-inert atmosphere, which could lead to various levels of problems or even complete failure. Another significant aspect is that a key performance indicator in medicinal chemistry is the capability to make novel chemical compounds amenable to patent protection. This “race” into the unknown will inevitably demand the discovery and development of unprecedented synthetic methodologies, which eventually will have to prove their capabilities on a larger scale. Finally, in times where green chemistry and sustainability are top-rated criteria for any chemical process, there is bound to be a major reluctance to apply procedures that cannot guarantee the highest level of environmental concern for both ethical and legal reasons. © 2023 The Author(s)
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| 10. |
- Fonseca, Daniela, et al.
(författare)
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Sustainable OrganoCatalyzed Enantioselective Catalytic Michael Additions in Betaine derived Deep Eutectic Solvents
- 2023
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Ingår i: SynOpen. - : Georg Thieme Verlag. - 2509-9396. ; 7:3, s. 374-
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Tidskriftsartikel (refereegranskat)abstract
- The catalyst cinchonidine-squaramide was immobilized within three different deep eutectic solvents (DES): (Betaine: D-Sorbitol: Water), (Betaine: D-Xylitol: Water) and (Betaine: D-Mannitol: Water) and evaluated in a well-known asymmetric Michael addition. These reactions provided excellent yields (up to 99%) and enantioselectivities (up to 98%) using only 1 mol% of catalyst. It was also possible to achieve 9 cycles in reactions with DES (Betaine: D-Sorbitol: Water), proving the high recyclability of this system. In the reactions realized with only 0.5 mol% of catalyst, it was possible to achieve 5 cycles and the products were obtained with high yields (up to 95%) and excellent enantioselectivities (up to 94%), using DES (Betaine: D-Sorbitol: Water)..
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