Late-stage C–H functionalization offers new opportunities in drug discovery

Nature Reviews Chemistry, Journal Year: 2021, Volume and Issue: 5(8), P. 522 - 545

Published: July 13, 2021

Language: Английский

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Rational Design of Bioinspired Catalysts for Selective Oxidations

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(15), P. 8611 - 8631

Published: July 2, 2020

Recognizing Nature's unique ability to perform challenging oxygenation reactions with exquisite selectivity parameters at iron-dependent oxygenases, chemists have long sought understand and mimic these enzymatic processes artificial systems. In the last two decades, replication of reactivity non-heme iron oxygenases has become feasible even simple coordination complexes manganese. A bona fide minimalistic functional model was tetradentate-N4 ligand based complex [Fe(tpa)(CH3CN)2]2+(Fe(tpa), tpa = tris(2-methylpyridyl)amine), which activates H2O2 via a mechanism that mirrors key steps O2 activation mononuclear centers: controlled O–O bond cleavage, generation high-valent Fe═O oxidant, promotion almost full spectrum its oxidative (C–H hydroxylation, olefin epoxidation, syn-dihydroxylation, desaturation). These landmark discoveries set mechanistic framework use nitrogen-rich ligands as catalysts for oxidizing organic substrates under synthetically relevant conditions. Due proof-of-concept demonstrations potential in synthesis, this chemistry flourished over past decade. parallel realization class diverse transformations, effort been spent manipulate catalyst structure aim tuning both oxidation reactions. This perspective provides an overview progress research. Some features archetypical Fe(tpa) stayed surprisingly true throughout evolution, but series alterations modulate electronic, steric, or binding properties allowed rational elicitation specific selectivity. some cases, replacement by manganese also proven beneficial. Overall, optimization enabled development highly asymmetric site-selective enantioselective C–H

Language: Английский

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Diversification of aliphatic C–H bonds in small molecules and polyolefins through radical chain transfer

Science, Journal Year: 2022, Volume and Issue: 375(6580), P. 545 - 550

Published: Feb. 3, 2022

The ability to selectively introduce diverse functionality onto hydrocarbons is of substantial value in the synthesis both small molecules and polymers. Herein, we report an approach aliphatic carbon-hydrogen bond diversification using radical chain transfer featuring easily prepared

Language: Английский

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Skeletal Editing: Interconversion of Arenes and Heteroarenes

Helvetica Chimica Acta, Journal Year: 2023, Volume and Issue: 106(3)

Published: Jan. 13, 2023

Abstract Skeletal editing involves making specific point‐changes to the core of a molecule through selective insertion, deletion or exchange atoms. It thus represents potentially powerful strategy for step‐economic modification complex substrates and is perfect complement methods such as C−H functionalization that target molecular periphery. Given their ubiquity in biologically active compounds, ability perform skeletal on – therefore interconvert between aromatic heterocycles especially valuable. This review summarizes both recent key historical examples applied interconversion rings; we anticipate it will serve highlight not only innovative enabling nature current methods, but also tremendous opportunities still exist field.

Language: Английский

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Skeletal Editing of (Hetero)Arenes Using Carbenes

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(42)

Published: May 26, 2023

Abstract (Hetero)arenes continue to prove their indispensability in pharmaceuticals, materials science, and synthetic chemistry. As such, the controllable modification of biologically significant (hetero)arenes towards diverse more‐potent complex molecular scaffolds through peripheral skeletal editing has been considered a challenging goal organic Despite many excellent reviews on ( i. e ., C−H functionalization) (hetero)arenes, editings via single atom insertion, deletion, or transmutations have received less attention review literature. In this review, we systematically summarize state‐of‐the‐art reactions using carbenes, with focus general mechanistic considerations applications natural product syntheses. The potential opportunities inherent challenges encountered while developing these strategies are also highlighted.

Language: Английский

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Regioselective aliphatic C–H functionalization using frustrated radical pairs

Nature, Journal Year: 2023, Volume and Issue: 619(7970), P. 514 - 520

Published: July 5, 2023

Language: Английский

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Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(22), P. 12313 - 12370

Published: Nov. 9, 2023

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of synthesis natural products, drugs, and complex compounds. It is anticipated that late-stage would improve drug discovery's effectiveness efficiency hasten creation various chemical libraries. Consequently, products a productive technique to produce product derivatives, which significantly impacts biology development. Carbon-carbon bonds make up fundamental framework organic molecules. Compared with carbon-carbon bond construction, activation can directly enable molecular editing (deletion, insertion, atoms groups atoms) provide more efficient accurate synthetic strategy. However, selective unstrained still one most challenging projects in synthesis. This review encompasses strategies employed recent years for cleavage by explicitly focusing on their applicability functionalization. expands current discourse reactions providing comprehensive overview types bonds. includes C-C(sp), C-C(sp2), C-C(sp3) single bonds; double triple bonds, focus catalysis transition metals organocatalysts. Additionally, specific topics, such as ring-opening processes involving three-, four-, five-, six-membered rings, are discussed, exemplar applications these techniques showcased context bioactive molecules discovery. aims shed light advancements field propose potential avenues future research realm

Language: Английский

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Copper-catalysed dehydrogenation or lactonization of C(sp3)–H bonds

Nature, Journal Year: 2024, Volume and Issue: 629(8011), P. 363 - 369

Published: March 28, 2024

Language: Английский

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Light-activated hypervalent iodine agents enable diverse aliphatic C–H functionalization

Nature Chemistry, Journal Year: 2025, Volume and Issue: 17(3), P. 365 - 372

Published: Feb. 24, 2025

Language: Английский

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Divergent synthesis of complex diterpenes through a hybrid oxidative approach

Science, Journal Year: 2020, Volume and Issue: 369(6505), P. 799 - 806

Published: Aug. 14, 2020

Trio of enzymes power divergent synthesis Diterpene natural products are built from a 20-carbon building block, with huge range possible structures and modifications. Chemical specific molecules, some which have valuable biological activities, is tricky because the need for selective oxidations rearrangements when starting widely available scaffolds. Zhang et al. characterized selectivities three oxidative that each attack different positions on common scaffold. They then seamlessly combined chemical transformations enzymatic to produce nine distinct compounds across families diterpenes. These results highlight potential hybrid organic-biocatalytic synthetic schemes synthesis. Science , this issue p. 799

Language: Английский

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