Visible Light-Driven Radical-Mediated C–C Bond Cleavage/Functionalization in Organic Synthesis

Chemical Reviews, Год журнала: 2020, Номер 121(1), С. 506 - 561

Опубликована: Май 29, 2020

Thermal C–C bond cleavage reactions allow the construction of structurally diverse molecular skeletons via predictable and efficient reorganizations. Visible light photoredox-catalyzed radical-mediated have recently emerged as a powerful alternative method for overcoming thermodynamic kinetic barrier in scaffolds. In recent years, plethora elegant useful been invented, products are sometimes otherwise inaccessible by classic thermal reactions. Considering great influence synthetic potential these reactions, we provide summary state art visible light-driven cleavage/functionalization strategies with specific emphasis on working models. We hoped that this review will be medicinal organic chemists inspire further reaction development interesting area.

Язык: Английский

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Bioisosteres of the Phenyl Ring: Recent Strategic Applications in Lead Optimization and Drug Design

Journal of Medicinal Chemistry, Год журнала: 2021, Номер 64(19), С. 14046 - 14128

Опубликована: Сен. 30, 2021

The benzene moiety is the most prevalent ring system in marketed drugs, underscoring its historic popularity drug design either as a pharmacophore or scaffold that projects pharmacophoric elements. However, introspective analyses of medicinal chemistry practices at beginning 21st century highlighted indiscriminate deployment phenyl rings an important contributor to poor physicochemical properties advanced molecules, which limited their prospects being developed into effective drugs. This Perspective deliberates on and applications bioisosteric replacements for have provided practical solutions range developability problems frequently encountered lead optimization campaigns. While effect compound contextual nature, substitution can enhanced potency, solubility, metabolic stability while reducing lipophilicity, plasma protein binding, phospholipidosis potential, inhibition cytochrome P450 enzymes hERG channel.

Язык: Английский

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Photocatalysis in the Life Science Industry

Chemical Reviews, Год журнала: 2021, Номер 122(2), С. 2907 - 2980

Опубликована: Сен. 24, 2021

In the pursuit of new pharmaceuticals and agrochemicals, chemists in life science industry require access to mild robust synthetic methodologies systematically modify chemical structures, explore novel space, enable efficient synthesis. this context, photocatalysis has emerged as a powerful technology for synthesis complex often highly functionalized molecules. This Review aims summarize published contributions field from industry, including research industrial-academic partnerships. An overview developed strategic applications synthesis, peptide functionalization, isotope labeling, both DNA-encoded traditional library is provided, along with summary state-of-the-art photoreactor effective upscaling photocatalytic reactions.

Язык: Английский

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Strain-Release [2π + 2σ] Cycloadditions for the Synthesis of Bicyclo[2.1.1]hexanes Initiated by Energy Transfer

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(18), С. 7988 - 7994

Опубликована: Апрель 27, 2022

Saturated bicycles are becoming ever more important in the design and development of new pharmaceuticals. Here a strategy for synthesis bicyclo[2.1.1]hexanes is described. These significant because they have defined exit vectors, yet many substitution patterns underexplored as building blocks. The process involves sensitization bicyclo[1.1.0]butane followed by cycloaddition with an alkene. scope mechanistic details method discussed.

Язык: Английский

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Strain release – an old tool for new transformations

Chemical Communications, Год журнала: 2020, Номер 56(43), С. 5718 - 5734

Опубликована: Янв. 1, 2020

This Feature Article provides an overview of research advances in the chemistry spring-loaded molecules, focusing mainly on strain-release transformations.

Язык: Английский

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Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane

Nature, Год журнала: 2022, Номер 611(7937), С. 721 - 726

Опубликована: Сен. 15, 2022

Язык: Английский

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An intramolecular coupling approach to alkyl bioisosteres for the synthesis of multisubstituted bicycloalkyl boronates

Nature Chemistry, Год журнала: 2021, Номер 13(10), С. 950 - 955

Опубликована: Сен. 28, 2021

Язык: Английский

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Synthesis of Polysubstituted 2-Oxabicyclo[2.1.1]hexanes via Visible-Light-Induced Energy Transfer

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(44), С. 20207 - 20213

Опубликована: Окт. 27, 2022

Synthesis of bicyclic scaffolds has attracted growing interest because they are high importance in modern pharmaceutical development. Here we report a strategy to access polysubstituted 2-oxabicyclo[2.1.1]hexanes single operation from readily accessible benzoylformate esters and bicyclo[1.1.0]butanes via visible-light-induced triplet energy transfer catalysis. The process is proposed involve formal [2π + 2σ] photocycloaddition/backbone C-H abstraction/aryl group migration sequence. A diverse range (hetero)aryl groups successfully underwent the backbone (C2) position provide previously inaccessible molecules, ester product can serve as handle for downstream manipulation, thus offering opportunities rapidly build up molecular complexity new sp3-rich chemical space.

Язык: Английский

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Catalytic Formal [2π+2σ] Cycloaddition of Aldehydes with Bicyclobutanes: Expedient Access to Polysubstituted 2‐Oxabicyclo[2.1.1]hexanes

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(34)

Опубликована: Июнь 12, 2023

Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres benzenoids in modern drug discovery. Here, we report a BF3 -catalyzed [2π+2σ] cycloaddition aldehydes with bicyclo[1.1.0]butanes (BCBs) to access polysubstituted 2-oxabicyclo[2.1.1]hexanes. A new kind BCB containing acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides be utilized substrates undergo BCBs after situ rearrangement aldehydes. We anticipate that our results will promote challenging sp3 -rich frameworks exploration BCB-based chemistry.

Язык: Английский

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A Practical and Scalable Approach to Fluoro‐Substituted Bicyclo[1.1.1]pentanes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(29)

Опубликована: Май 31, 2022

After more than 20 years of trials, a practical scalable approach to fluoro-substituted bicyclo[1.1.1]pentanes (F-BCPs) has been developed. The physicochemical properties the F-BCPs have studied, and core was incorporated into structure anti-inflammatory drug Flurbiprofen in place fluorophenyl ring.

Язык: Английский

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