Deuterium in drug discovery: progress, opportunities and challenges

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(7), P. 562 - 584

Published: June 5, 2023

Language: Английский

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Electrochemical Late-Stage Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(19), P. 11269 - 11335

Published: Sept. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Language: Английский

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Radical deuteration

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(15), P. 6291 - 6306

Published: Jan. 1, 2022

This review is a systematic summary of radical deuteration with four reaction types: reductive deuteration, defunctionalization–deuteration, hydrogen–deuterium (H/D) exchange and deuteroalkylation.

Language: Английский

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Site-Specific and Degree-Controlled Alkyl Deuteration via Cu-Catalyzed Redox-Neutral Deacylation

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(22), P. 9570 - 9575

Published: May 25, 2022

Deuterated organic compounds have become increasingly important in many areas; however, it remains challenging to install deuterium site-selectively unactivated aliphatic positions with control of the degree deuteration. Here, we report a Cu-catalyzed degree-controlled deacylative deuteration diverse alkyl groups methylketone (acetyl) moiety as traceless activating group. The use N-methylpicolino-hydrazonamide (MPHA) promotes efficient aromatization-driven C–C cleavage. Mono-, di-, and trideuteration at specific sites can be selectively achieved. reaction is redox-neutral broad functional group tolerance. utility this method has been demonstrated forming complete set deuterated ethyl groups, merging Diels–Alder reaction, net devinylative deuteration, synthesis d2-analogue Austedo.

Language: Английский

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Chemoselective Decarboxylative Protonation Enabled by Cooperative Earth‐Abundant Element Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(3)

Published: Nov. 9, 2022

Decarboxylative protonation is a general deletion tactic to replace polar carboxylic acid groups with hydrogen or its isotope. Current methods rely on the pre-activation of acids, non-sustainable sources, and/or expensive/highly oxidizing photocatalysts, presenting challenges their wide adoption. Here we show that cooperative iron/thiol catalyst system can readily achieve this transformation, hydrodecarboxylating range activated and unactivated acids overcoming scope limitations in previous direct methods. The reaction scaled batch configuration be directly performed deuterated solvent afford high yields d-incorporated products excellent isotope incorporation efficiency; characteristics not attainable photocatalyzed approaches. Preliminary mechanistic studies indicate radical mechanism kinetic results (KIE=1) are consistent light-limited reaction.

Language: Английский

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Photocatalytic Deuterium Atom Transfer Deuteration of Electron‐Deficient Alkenes with High Functional Group Tolerance

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(3)

Published: Nov. 17, 2022

Abstract Due to its mild reaction conditions and unique chemoselectivity, hydrogen atom transfer (HAT) hydrogenation represents an indispensable method for the synthesis of complex molecules. Its analog using deuterium, deuterium (DAT) deuteration, is expected enable access deuterium‐labeled compounds. However, DAT deuteration has been scarcely studied synthetic purposes, a that possesses favorable characteristics HAT hydrogenations remained elusive. Herein, we report protocol photocatalytic electron‐deficient alkenes. In contrast previous this tolerates variety synthetically useful functional groups including haloarenes. The late‐stage also allows deuterated amino acids as well donepezil‐ d 2 . Thus, work demonstrates potential chemistry become alternative choice preparing deuterium‐containing

Language: Английский

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Recent Advances in Deuteration Reactions^†

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 42(10), P. 1145 - 1156

Published: Dec. 26, 2023

Comprehensive Summary The deuteration of organic compounds has attracted more attentions in recent years for the potential applications new drug discovery and synthetic chemistry. For this purpose, many efficient deuterium labeling methodologies have been developed, including hydrogen isotope exchange (HIE), reductive deuteration, dehalogenative that allow synthesis selectively deuterated compounds. In last few years, great breakthroughs selective achieved interest molecules is rising. review, we summarized developments since 2021. Several types key processes incorporation reactions, H/D exchange, are introduced discussed. Key Scientists 2000s, Derdau Atzrodt's group made contributions to directing assisted noble‐metal catalyzed arenes labeled During same period, Sajiki co‐workers completed a series reactions by heterogeneous platinum‐group metal catalysts. Since 2015, Gregory Pieters developed ruthenium catalysts exchange. 2016, Chirik's presence homogeneous iron complex. David MacMillan coworkers photocatalyzed HIE α‐amino C(sp 3 )–H bonds. From 2020, nanoelectrodes were designed deuterations unactivated unsaturated bonds Zhang's group. Recently, Beller's several strategies isotopic using earth‐abundant Our review latest important

Language: Английский

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Ligand‐Enabled Palladium(II)‐Catalyzed Enantioselective β‐C(sp³)−H Arylation of Aliphatic Tertiary Amides**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(17)

Published: March 5, 2023

Amide is one of the most widespread functional groups in organic and bioorganic chemistry, it would be valuable to achieve stereoselective C(sp3 )-H functionalization amide molecules. Palladium(II) catalysis has been prevalently used C-H activation chemistry past decades, however, due weakly-coordinating feature simple amides, challenging their direct with enantiocontrol by PdII catalysis. Our group developed sulfoxide-2-hydroxypridine (SOHP) ligands, which exhibited remarkable activity Pd-catalyzed C(sp2 activation. In this work, we demonstrate that chiral SOHP ligands served as an ideal solution enantioselective amides. Herein, report efficient asymmetric /SOHP-catalyzed β-C(sp3 arylation aliphatic tertiary ligand plays a key role deprotonation-metalation step.

Language: Английский

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Metal-free photoinduced hydrogen atom transfer assisted C(sp³)–H thioarylation

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(9), P. 3431 - 3436

Published: Jan. 1, 2023

A mild metal-free approach for C(sp 3 )–H thioarylation of organic building blocks.

Language: Английский

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Hydrogenative alkene perdeuteration aided by a transient cooperative ligand

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(10), P. 1384 - 1390

Published: Sept. 4, 2023

Language: Английский

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