Metallaphotoredox: The Merger of Photoredox and Transition Metal Catalysis

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(2), P. 1485 - 1542

Published: Nov. 18, 2021

The merger of photoredox catalysis with transition metal catalysis, termed metallaphotoredox has become a mainstay in synthetic methodology over the past decade. Metallaphotoredox combined unparalleled capacity for bond formation broad utility photoinduced electron- and energy-transfer processes. Photocatalytic substrate activation allowed engagement simple starting materials metal-mediated bond-forming Moreover, electron or energy transfer directly key organometallic intermediates provided novel modes entirely complementary to traditional catalytic platforms. This Review details contextualizes advancements molecule construction brought forth by metallaphotocatalysis.

Language: Английский

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

Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 64(19), P. 14046 - 14128

Published: Sept. 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.

Language: Английский

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Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(8), P. 4237 - 4352

Published: Jan. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Language: Английский

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Photocatalysis in the Life Science Industry

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(2), P. 2907 - 2980

Published: Sept. 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.

Language: Английский

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Put a ring on it: application of small aliphatic rings in medicinal chemistry

RSC Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 12(4), P. 448 - 471

Published: Jan. 1, 2021

Aliphatic three- and four-membered rings including cyclopropanes, cyclobutanes, oxetanes, azetidines bicyclo[1.1.1]pentanes have been increasingly exploited in medicinal chemistry for their beneficial physicochemical properties applications as functional group bioisosteres. This review provides a historical perspective comparative up to date overview of commonly applied small rings, exemplifying key principles with recent literature examples. In addition describing the merits advantages each ring system, potential hazards liabilities are also illustrated explained, any significant chemical or metabolic stability toxicity risks.

Language: Английский

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Copper-mediated synthesis of drug-like bicyclopentanes

Nature, Journal Year: 2020, Volume and Issue: 580(7802), P. 220 - 226

Published: Feb. 17, 2020

Language: Английский

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Intermolecular [2π+2σ]-photocycloaddition enabled by triplet energy transfer

Nature, Journal Year: 2022, Volume and Issue: 605(7910), P. 477 - 482

Published: March 21, 2022

Language: Английский

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A Radical Approach to Anionic Chemistry: Synthesis of Ketones, Alcohols, and Amines

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(16), P. 6726 - 6739

Published: April 3, 2019

Historically accessed through two-electron, anionic chemistry, ketones, alcohols, and amines are of foundational importance to the practice organic synthesis. After placing this work in proper historical context, Article reports development, full scope, a mechanistic picture for strikingly different way forging such functional groups. Thus, carboxylic acids, once converted redox-active esters (RAEs), can be utilized as formally nucleophilic coupling partners with other derivatives (to produce ketones), imines benzylic amines), or aldehydes alcohols). The reactions uniformly mild, operationally simple, and, case ketone synthesis, broad scope (including several applications simplification synthetic problems parallel synthesis). Finally, an extensive study synthesis is performed trace elementary steps catalytic cycle provide end-user clear understandable rationale selectivity, role additives, underlying driving forces involved.

Language: 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, Journal Year: 2022, Volume and Issue: 144(18), P. 7988 - 7994

Published: April 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.

Language: Английский

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Photochemical intermolecular dearomative cycloaddition of bicyclic azaarenes with alkenes

Science, Journal Year: 2021, Volume and Issue: 371(6536), P. 1338 - 1345

Published: March 25, 2021

Heteroaromatics lured into cycloadditions The Diels-Alder reaction is widely used to produce six-membered carbon rings from alkenes and dienes. such as quinolines resemble dienes in principle, but practice their pairs of double bonds are inert toward because aromatic stabilization. Ma et al. report that by using an iridium photosensitizer, they could excite related azaarenes triplet states, thereby disrupting the aromaticity enabling intermolecular, Diels-Alder–like reactivity (see Perspective Schmidt). reactions proceeded exclusively at flanking carbons outside nitrogen-containing ring. Science , this issue p. 1338 ; see also 1313

Language: Английский

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