Enantioselective Transformations in the Synthesis of Therapeutic Agents

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(15), P. 9397 - 9446

Published: July 7, 2023

The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, efficient synthesis enantiopure pharmaceuticals or their synthetic intermediates poses profound challenge to medicinal process chemists. significant advancement in asymmetric catalysis provided an effective reliable solution this challenge. successful application transition metal catalysis, organocatalysis, biocatalysis pharmaceutical industries promoted discovery by precise preparation enantio-enriched therapeutic agents, facilitated industrial production active ingredient economic environmentally friendly fashion. present review summarizes most recent applications (2008–2022) industry ranging from scales pilot levels. It also showcases latest achievements trends agents with state art technologies catalysis.

Language: Английский

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Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9045 - 9062

Published: March 15, 2024

Methods for the synthesis of α-branched alkylamines are important due to their ubiquity in biologically active molecules. Despite development many methods amine preparation, C(sp3)-rich nitrogen-containing compounds continue pose challenges synthesis. While carbonyl reductive amination (CRA) between ketones and is cornerstone method alkylamine synthesis, it sometimes limited by sterically demanding condensation step dialkyl amines more restricted availability compared aldehydes. We recently reported a "higher-order" variant this transformation, alkylative (CAA), which utilized halogen atom transfer (XAT)-mediated radical mechanism, enabling streamlined complex alkylamines. efficacy visible-light-driven approach, displayed scalability issues, competitive was problem certain substrate classes, limiting applicability. Here, we report change reaction regime that expands CAA platform through realization an extremely broad zinc-mediated reaction. This new strategy enabled elimination CRA, simplified purification, improved scope. Furthermore, harnessed carboxylic acid derivatives as alkyl donors facilitated α-trialkyl tertiary amines, cannot be accessed via CRA. Zn-mediated can carried out at variety scales, from 10 μmol setup microtiter plates high-throughput experimentation, gram-scale medicinally-relevant compounds. believe transformation enables robust, efficient, economical access provides viable alternative current benchmark methods.

Language: Английский

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Reductive aminations by imine reductases: from milligrams to tons

Chemical Science, Journal Year: 2022, Volume and Issue: 13(17), P. 4697 - 4713

Published: Jan. 1, 2022

IRED-catalyzed reductive aminations have progressed from mg to ton scale, through advances in enzyme discovery, protein engineering and process biocatalysis.

Language: Английский

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Organometallic Mn(I) Complexes in Asymmetric Catalytic (Transfer) Hydrogenation and Related Transformations

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(14)

Published: March 7, 2024

Abstract Direct asymmetric hydrogenation (AH) and transfer (ATH) are among the most efficient approaches to produce chiral building blocks. Recently, these types of transformations have witnessed a shift towards use molecular catalysts based on earth‐abundant transition metals due their ready availability, economic advantage, novel properties. With particular regard manganese, catalyst development has seen both efficiency substrate scope in AH ATH greatly improved, with emergence large number well‐defined Mn‐complexes employed this field. The reaction includes C=O bonds, reduction C=N bonds reductive C=C bonds. Herein, our survey area focuses catalytic activity such complexes, versatility routes convert substrates target molecules. We consider collected findings article will be helpful reader by providing an insight into ligand design, thereby aiding future development. Moreover, review is aimed at highlighting remarkable progress made last seven years manganese complexes for enantioselective reduction.

Language: Английский

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Impact of aqueous micellar media on biocatalytic transformations involving transaminase (ATA); applications to chemoenzymatic catalysis

Green Chemistry, Journal Year: 2022, Volume and Issue: 24(16), P. 6172 - 6178

Published: Jan. 1, 2022

Surfactant-enabled asymmetric ATA-catalyzed reductive aminations in aqueous buffered media are described, representative of the enhanced levels conversion made possible by presence a nonionic surfactant water, thereby enabling 1-pot chemoenzymatic catalysis.

Language: Английский

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Organocatalytic Dynamic Kinetic Resolution: An Update

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(7)

Published: Feb. 17, 2022

Abstract It is only in the two last decades that first examples of organocatalytic dynamic kinetic resolutions (DKRs) have been disclosed. These methodologies allow resolving racemic compounds with up to quantitative yield. Today, a variety chiral organocatalysts are capable providing excellent enantioselectivities many types transformations evolving through DKR. The goal this review update field DKRs since 2016. divided into six sections, according different employed these reactions, such as Brønsted acid catalysts, hydrogen‐bonding N‐heterocyclic carbene Lewis base phase‐transfer and cinchona alkaloid‐based catalysts.

Language: Английский

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Asymmetric Double Hydroxycarbonylation of Alkynes to Chiral Succinic Acids Enabled by Palladium Relay Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(29)

Published: May 7, 2022

Abstract A Pd‐catalyzed asymmetric double hydroxycarbonylation of terminal alkynes was developed by using relay catalysis, providing a highly efficient route to chiral succinic acids (41 examples, 76–94 %, 94–99 % ee ). Key success the combinatorial use Pd precursor with two distinct phosphine ligands in one pot. The synthetic utilities this protocol were showcased facile synthesis key intermediates for pharmaceuticals.

Language: Английский

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Leveraging the Redox Promiscuity of Nickel To Catalyze C–N Coupling Reactions

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 17, 2024

This perspective details advances made in the field of Ni-catalyzed C–N bond formation. The use this Earth abundant metal to decorate amines, amides, lactams, and heterocycles enables direct access a variety biologically active industrially relevant compounds sustainable manner. Herein, different strategies that leverage propensity Ni facilitate both one- two-electron processes will be surveyed. first part Perspective focuses on couplings at room temperature by accessing oxidized Ni(III) intermediates. In context, photochemical, electrochemical, chemically mediated analyzed. A special emphasis has been put providing comprehensive explanation mechanistic avenues have proposed these chemistries; either Ni(I/III) self-sustained cycles or Ni(0/II/III) photochemically pathways. second ligand designs also enable reactivity via Ni(0/II) mechanism. Finally, we discuss our thoughts possible future directions field.

Language: Английский

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Iridium-catalyzed direct asymmetric reductive amination utilizing primary alkyl amines as the N-sources

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 10, 2022

Abstract Direct asymmetric reductive amination is one of the most efficient methods for construction chiral amines, in which scope applicable amine coupling partners remains a significant challenge. In this study we describe primary alkyl amines effectively serve as N-sources direct catalyzed by iridium precursor and sterically tunable phosphoramidite ligands. The density functional theory studies reaction mechanism imply substrates ligand strengthened (N)H-O(P) hydrogen-bonding attraction, hydride addition occurs via an outer-sphere transition state, Cl-H H-bonding plays important role. Through concise procedure, cinacalcet, tecalcet, fendiline many other related have been synthesized single step with high yields excellent enantioselectivity.

Language: Английский

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The lower the better: Efficient carbonylative reactions under atmospheric pressure of carbon monoxide

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 475, P. 214900 - 214900

Published: Oct. 31, 2022

Language: Английский

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