Spirocyclic Scaffolds in Medicinal Chemistry

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 64(1), P. 150 - 183

Published: Dec. 31, 2020

Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest less planar bioactive compounds has given rise to the development of synthetic methodologies for preparation spirocyclic scaffolds. In this Perspective, we summarize diverse routes obtain systems. impact spirocycles on potency selectivity, including aspect stereochemistry, is discussed. Furthermore, examine changes physicochemical properties as well vitro vivo ADME using selected studies that compare their nonspirocyclic counterparts. conclusion, value medicinal chemistry

Language: Английский

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Catalytic Enantioselective Construction of Spiro Quaternary Carbon Stereocenters

ACS Catalysis, Journal Year: 2019, Volume and Issue: 9(3), P. 1820 - 1882

Published: Jan. 31, 2019

The catalytic enantioselective assembly of spirocyclic molecules featuring a spiro quaternary carbon stereocenter is currently great interest because such privileged 3D structures are widely present in natural products that exhibit broad spectrum biological and pharmacological activities. This review summarizes the advances based on six major synthetic strategies showcases reaction mechanisms detail. advantages limitations each strategy presented, remaining opportunities outlined.

Language: Английский

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Stereoselective synthesis and applications of spirocyclic oxindoles

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(5), P. 1026 - 1084

Published: Jan. 1, 2021

This review summaries recent synthetic developments towards spirocyclic oxindoles and applications as valuable medicinal targets.

Language: Английский

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Chiral Cyclopentadienyl Ligands: Design, Syntheses, and Applications in Asymmetric Catalysis

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(24), P. 13198 - 13224

Published: July 16, 2020

The creation of new chiral ligands capable providing high stereocontrol in metal-catalyzed reactions is crucial modern organic synthesis. production bioactive molecules as single enantiomers increasingly required, and asymmetric catalysis with metal complexes constitutes one the most efficient synthetic strategies to access optically active compounds. Herein we offer a historical overview on development derivatives ubiquitous cyclopentadienyl ligand (CpX ), detail their successful application broad range transformations. Those include functionalization challenging C-H bonds beyond, giving an extensive catalogue valuable molecules. A critical comparison existing families, design, synthesis, complexation different metals also provided. In addition, future research directions are discussed further enhance performance CpX enantioselective catalysis.

Language: Английский

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Enantio‐ and Diastereodivergent Synthesis of Spirocycles through Dual‐Metal‐Catalyzed [3+2] Annulation of 2‐Vinyloxiranes with Nucleophilic Dipoles

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(47), P. 24941 - 24949

Published: Sept. 17, 2021

The development of efficient and straightforward methods for obtaining all optically active isomers structurally rigid spirocycles from readily available starting materials is great value in drug discovery chiral ligand development. However, the stereodivergent synthesis bearing multiple stereocenters remains an unsolved challenge owing to steric hindrance ring strain. Herein, we report enantio- diastereodivergent through dual-metal-catalyzed [3+2] annulation oxy π-allyl metallic dipoles with less commonly employed nucleophilic (imino esters). A series spiro compounds a pyrroline olefin were easily synthesized manner (up 19:1 dr, >99 % ee), which showed promise as new type N-olefin ligand. Preliminary mechanistic studies also carried out understand process this bimetallic catalysis.

Language: Английский

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Electrochemical electrophilic bromination/spirocyclization of N-benzyl-acrylamides to brominated 2-azaspiro[4.5]decanes

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(9), P. 3543 - 3548

Published: Jan. 1, 2023

An electrochemical electrophilic bromination/spirocyclization of N -benzyl-acrylamides to brominated 2-azaspiro[4.5]decanes with 2-bromoethan-1-ol as the brominating reagent has been developed.

Language: Английский

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Spiroindoles as Intermediates/Products in Transition Metal-Catalyzed Dearomatization of Indoles

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(14), P. 9442 - 9475

Published: July 3, 2023

Spirocyclic indole derivatives are fascinating tridimensional molecular scaffolds from both a synthetic and biological point of view. Among the many strategies developed to access these structures, transition metal catalysis has recently led impressive advances, especially relying on unique reactivity dearomatized spirocyclic intermediates. These species can indeed evolve toward or nonspirocyclic products through rearomatization-driven processes, which at same time highly challenging control but also source large structural diversity. This review highlights most prominent methods past decade that involve spirocyclization tethered functional group may be activated by metal, leading rearomatized products. The discussion is particularly focused spiroindoleninium intermediate complex mechanistic features regarding its evolution, dependent catalytic systems.

Language: Английский

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The chemistry of heterocycles in the 21st century

Russian Chemical Reviews, Journal Year: 2024, Volume and Issue: 93(7), P. RCR5125 - RCR5125

Published: July 1, 2024

The chemistry of heterocyclic compounds has traditionally been and remains a bright area chemical science in Russia. This is due to the fact that many heterocycles find widest application. These are key structural fragments most drugs, plant protection agents. Many natural also derivatives heterocycles. At present, more than half hundreds millions known collective review devoted achievements Russian chemists this field over last 15–20 years. presents leading heterocyclists representing both RAS institutes university science. It worth noting wide scope review, terms geography author teams, covering whole our large country, diversity research areas. Practically all major types represented review. special attention focused on practical applications design new drugs biologically active compounds, high-energy molecules, materials for organic electronics photovoltaics, ligands coordination chemistry, other rapidly developing advances would not be possible without development fundamental transformations chemistry.<br> Bibliography — 2237 references.

Language: Английский

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Recent advances in microwave-assisted multicomponent synthesis of spiro heterocycles

RSC Advances, Journal Year: 2024, Volume and Issue: 14(8), P. 5547 - 5565

Published: Jan. 1, 2024

Spiro heterocycle frameworks are a class of organic compounds that possesses unique structural features making them highly sought-after targets in drug discovery due to their diverse biological and pharmacological activities.

Language: Английский

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Rhodium(III)‐Catalyzed Asymmetric Access to Spirocycles through C−H Activation and Axial‐to‐Central Chirality Transfer

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(18), P. 7188 - 7192

Published: Feb. 3, 2020

Axial-to-central chirality transfer is an important strategy to construct chiral centers, where the axially reagents are mostly limited atropomerically stable ones. Reported herein a RhIII -catalyzed enantioselective spiroannulative synthesis of nitrones. The coupling proceeds via C-H arylation give metastable biaryl, followed by intramolecular dearomative trapping under oxidative conditions with high degree transfer.

Language: Английский

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