Piperidine Derivatives: Recent Advances in Synthesis and Pharmacological Applications

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2937 - 2937

Published: Feb. 2, 2023

Piperidines are among the most important synthetic fragments for designing drugs and play a significant role in pharmaceutical industry. Their derivatives present more than twenty classes of pharmaceuticals, as well alkaloids. The current review summarizes recent scientific literature on intra- intermolecular reactions leading to formation various piperidine derivatives: substituted piperidines, spiropiperidines, condensed piperidinones. Moreover, applications natural piperidines were covered, latest advances discovery biological evaluation potential containing moiety. This is designed help both novice researchers taking their first steps this field experienced scientists looking suitable substrates synthesis biologically active piperidines.

Language: Английский

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Asymmetric arene hydrogenation: towards sustainability and application

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(15), P. 4996 - 5012

Published: Jan. 1, 2023

This review summarises the state-of-the-art in transition-metal catalysed asymmetric hydrogenation of (hetero)arenes and highlights recent advances with a special focus on sustainability while also addressing its shortcomings.

Language: Английский

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Introducing Frustrated Lewis Pairs to Metal–Organic Framework for Selective Hydrogenation ofN-Heterocycles

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(27), P. 14994 - 15000

Published: June 29, 2023

Hydrogenated nitrogen heterocyclic compounds play a critical role in the pharmaceutical, polymer, and agrochemical industries. Recent studies on partial hydrogenation of have focused costly toxic precious metal catalysts. As an important class main-group catalysts, frustrated Lewis pairs (FLPs) been widely applied catalytic reactions. In principle, combination FLPs metal-organic framework (MOF) is anticipated to efficiently enhance recyclability performance FLPs; however, previously studied MOF-FLPs showed low reactivity N-heterocycles compounds. Herein, we offer novel P/B type MOF-FLP catalyst that was achieved via solvent-assisted linker incorporation approach boost Using hydrogen gas under moderate pressure, proposed can serve as highly efficient heterogeneous for selective quinoline indole tetrahydroquinoline indoline-type drug high yield excellent recyclability.

Language: Английский

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Translating Planar Heterocycles into Three‐Dimensional Analogs by Photoinduced Hydrocarboxylation**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(30)

Published: May 18, 2023

The rapid preparation of complex three-dimensional (3D) heterocyclic scaffolds is a key challenge in modern medicinal chemistry. Despite the increased probability clinical success for small molecule therapeutic candidates with 3D complexity, new drug targets remain dominated by flat molecules due to abundance coupling reactions available their construction. In principle, heteroarene hydrofunctionalization offer an opportunity transform readily accessible planar into more three-dimensionally analogs through introduction single molecular vector. Unfortunately, dearomative limited. Herein, we report strategy enable hydrocarboxylation indoles and related heterocycles. This reaction represents rare example that meets numerous requirements broad implementation discovery. transformation highly chemoselective, scope, operationally simple, amenable high-throughput experimentation (HTE). Accordingly, this process will allow existing libraries heteroaromatic compounds be translated diverse exploration classes medicinally relevant molecules.

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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Dynamic Kinetic Resolution-Based Asymmetric Transfer Hydrogenation of Racemic 2-Substituted Quinolines

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

The synthesis of chiral tetrahydroquinolines (THQs) has garnered significant interest from medicinal chemists due to their frequent presence as pharmacophores in bioactive compounds. While existing synthetic methods have primarily focused on THQs with single or multiple endocyclic centers, the selective construction both endo- and exo-cyclic centers remains a challenge that requires further development. This study introduces dynamic kinetic resolution (DKR)-based transfer hydrogenation racemic 2-substituted quinolines, which yields structurally novel consecutive excellent stereoselectivities (59 examples, generally >20:1 dr >90% ee, up three stereocenters). Our approach offers mechanistically method for asymmetric transformation electron-deficient aromatic N-heterocycles presents an innovative way expand N-heterocycle chemical space chemistry.

Language: Английский

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Rhodium-Catalyzed Homogeneous Asymmetric Hydrogenation of Naphthol Derivatives

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Due to their strong aromaticity and difficulties in chemo-, regio-, enantioselectivity control, asymmetric hydrogenation of naphthol derivatives 1,2,3,4-tetrahydronaphthols has remained a long-standing challenge. Herein, we report the first example homogeneous catalyzed by tethered rhodium-diamine catalysts, affording wide array optically pure high yields with excellent enantioselectivities (up 98% yield >99% ee). Mechanistic studies experimental computational approaches reveal that fluorinated solvent 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) plays vital roles control reactivity selectivity, 1-naphthol is reduced via cascade reaction pathway, including dearomative tautomerization, 1,4-hydride addition, 1,2-hydride addition sequence. A novel synergistic activation mode was proposed which HFIP assists both hydrogen molecule presence base, situ-generated fleeting keto tautomer immediately trapped Rh(III)-H species before it escapes from cage. This protocol provides straightforward practical pathway for synthesis key intermediates several chiral drugs. Particularly, Nadolol, drug treatment hypertension, angina pectoris, congestive heart failure, certain arrhythmias, enantioselectively synthesized time.

Language: Английский

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Metal oxides confine single atoms toward efficient thermal catalysis

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 488, P. 215189 - 215189

Published: April 28, 2023

Language: Английский

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Chemoselective Quinoline and Isoquinoline Reduction by Energy Transfer Catalysis Enabled Hydrogen Atom Transfer

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(48)

Published: Oct. 7, 2023

(Hetero)arene reduction is one of the key avenues for synthesizing related cyclic alkenes and alkanes. While catalytic hydrogenation Birch are two broadly utilized approaches (hetero)arene across academia industry over last century, both methods have encountered significant chemoselectivity challenges. We hereby introduce a highly chemoselective quinoline isoquinoline protocol operating through selective energy transfer (EnT) catalysis, which enables subsequent hydrogen atom (HAT). The design this bypasses conventional metric reaction, that is, reductive potential, instead relies on triplet energies chemical moieties kinetic barriers events. Many reducing labile functional groups, were incompatible with previous reactions, retained in reaction. anticipate will trigger further advancement arene enable current arene-rich drug space to escape from flatland.

Language: Английский

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Asymmetric Hydrogenation of Racemic 2-Substituted Indoles via Dynamic Kinetic Resolution: An Easy Access to Chiral Indolines Bearing Vicinal Stereogenic Centers

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5081 - 5087

Published: Feb. 15, 2024

The asymmetric hydrogenation (AH) of N-unprotected indoles is a straightforward, yet challenging method to access biologically interesting NH chiral indolines. This has for years been limited 2/3-monosubstituted or 2,3-disubstituted indoles, which produce indolines bearing endocyclic centers. Herein, we have reported an innovative Pd-catalyzed AH racemic α-alkyl aryl-substituted indole-2-acetates using acid-assisted dynamic kinetic resolution (DKR) process, affording range structurally fascinating that contain exocyclic stereocenters with excellent yields, diastereoselectivities, and enantioselectivities. Mechanistic studies support the DKR process relies on rapid interconversion each enantiomer substrates, leveraged by acid-promoted isomerization between aromatic indole nonaromatic enamine intermediate. reaction can be performed gram scale, products derivatized into non-natural β-amino acids via facile debenzylation amino alcohol upon reduction.

Language: Английский

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