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      Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

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      Chemical Reviews
      American Chemical Society

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          Abstract

          Chiral amines are key structural motifs present in a wide variety of natural products, drugs, and other biologically active compounds. During the past decade, significant advances have been made with respect to the enantioselective synthesis of chiral amines, many of them based on catalytic asymmetric hydrogenation (AH). The present review covers the use of AH in the synthesis of chiral amines bearing a stereogenic center either in the α, β, or γ position with respect to the nitrogen atom, reported from 2010 to 2020. Therefore, we provide an overview of the recent advances in the AH of imines, enamides, enamines, allyl amines, and N-heteroaromatic compounds.

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          Fluorine in medicinal chemistry.

          It has become evident that fluorinated compounds have a remarkable record in medicinal chemistry and will play a continuing role in providing lead compounds for therapeutic applications. This tutorial review provides a sampling of renowned fluorinated drugs and their mode of action with a discussion clarifying the role and impact of fluorine substitution on drug potency.
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            Fluorine in pharmaceuticals: looking beyond intuition.

            Fluorine substituents have become a widespread and important drug component, their introduction facilitated by the development of safe and selective fluorinating agents. Organofluorine affects nearly all physical and adsorption, distribution, metabolism, and excretion properties of a lead compound. Its inductive effects are relatively well understood, enhancing bioavailability, for example, by reducing the basicity of neighboring amines. In contrast, exploration of the specific influence of carbon-fluorine single bonds on docking interactions, whether through direct contact with the protein or through stereoelectronic effects on molecular conformation of the drug, has only recently begun. Here, we review experimental progress in this vein and add complementary analysis based on comprehensive searches in the Cambridge Structural Database and the Protein Data Bank.
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              The medicinal chemist's toolbox: an analysis of reactions used in the pursuit of drug candidates.

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                Author and article information

                Journal
                Chem Rev
                Chem Rev
                cr
                chreay
                Chemical Reviews
                American Chemical Society
                0009-2665
                1520-6890
                22 October 2021
                12 January 2022
                : 122
                : 1
                : 269-339
                Affiliations
                []Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , Baldiri Reixac 10, Barcelona E-08028, Spain
                []Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Universitat de Barcelona , Martí i Franquès 1, Barcelona E-08028, Spain
                Author notes
                Author information
                https://orcid.org/0000-0001-5256-8798
                https://orcid.org/0000-0002-9229-969X
                https://orcid.org/0000-0001-7142-7675
                Article
                10.1021/acs.chemrev.1c00496
                9998038
                34677059
                c6c4445b-e4d7-4f0a-8144-fa9fe264c1d5
                © 2021 American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                Funding
                Funded by: Institute for Research in Biomedicine, doi 10.13039/100007678;
                Award ID: NA
                Funded by: Ministerio de Ciencia e Innovación, doi 10.13039/501100004837;
                Award ID: PID2020-119535RB-100
                Categories
                Review
                Custom metadata
                cr1c00496
                cr1c00496

                Chemistry
                Chemistry

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