Sulfonium Salts as Acceptors in Electron Donor‐Acceptor Complexes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(29)

Published: March 24, 2023

Abstract The photoactivation of electron donor‐acceptor complexes has emerged as a sustainable, selective and versatile strategy for the generation radical species. Electron (EDA) complexation, however, imposes electronic constraints on donor acceptor components this can limit range radicals that be generated using approach. New EDA complexation strategies exploiting sulfonium salts allow to from native functionality. For example, aryl salts, formed by activation arenes, serve in due their electron‐deficient nature. This “sulfonium tag” approach relaxes parent substrate dramatically expands complexation. In review, these new applications will introduced areas chemical space rendered accessible through innovation highlighted.

Language: Английский

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Photochemical Methods Applied to DNA Encoded Library (DEL) Synthesis

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(3), P. 385 - 401

Published: Jan. 19, 2023

ConspectusDNA-encoded library technology (DELT) is a new screening modality that allows efficient, cost-effective, and rapid identification of small molecules with potential biological activity. This emerging technique represents an enormous advancement that, in combination other technologies such as high-throughput (HTS), fragment-based lead generation, structure-based drug design, has the to transform how discovery carried out. DELT hybrid which chemically synthesized compounds are linked unique genetic tags (or "barcodes") contain readable information. In this way, millions billions building blocks (BBs) attached on-DNA via split-and-pool synthesis can be evaluated against target single experiment. Polymerase chain reaction (PCR) amplification next-generation sequencing (NGS) analysis sequence oligonucleotides DNA tag used identify those ligands high affinity for target. innovative fusion chemical was conceived 1992 by Brenner Lerner (Proc. Natl. Acad. Sci. 1992, 89, 5381–5383) under accelerated development implementation synthetic techniques protocols compatible DNA. fact, compatibility key parameter increasing chances ligand, central focus been transformations transition robust synthesis. Because sole use amplifiable barcode, its structural integrity during process mandatory. As such, these sensitive, polyfunctional substrates typically requires aqueous solutions within defined pH temperature ranges, considered notable challenge DEL synthesis.Using low-energy visible light driving force promote attractive alternative classical methods, it important well-established tool forging bonds way radical intermediates. Recent advances field photocatalysis extraordinary, powerful research arena still continuous development. Several applications taking advantage mild conditions photoinduced have directed toward synthesis, allowing expansion space available evaluation on-DNA. There no doubts visible-light-driven reactions become one most approaches DELT, given easy they provide construct challenges achieve equal success protocols.Key characteristics photocatalytic include short times efficiency, translate into retention integrity. Account, we describe recent diversification prepared on-DNA, highlighting amenability employed preserving structure molecules. We demonstrate from our group applicability summary table containing all methods reported date demonstrating their aspects scope, applications, compatibilities. With information, practitioners provided compelling reasons developing/choosing applications.

Language: Английский

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Evolution of chemistry and selection technology for DNA-encoded library

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(2), P. 492 - 516

Published: Oct. 11, 2023

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and non-self-replicating phenotypes, generating a diverse world. In analogy with biological world, DEL world can evolve by using central dogma, wherein DNA replicates PCR reactions to amplify genetic codes, sequencing transcripts information, DNA-compatible synthesis translates into phenotypes. Importantly, is key expanding space. Besides, evolution-driven selection system pushes chemicals under selective pressure, i.e., desired strategies. this perspective, we summarized recent advances in synthetic toolbox panning strategies, which will shed light on drug discovery harnessing vitro evolution via DEL.

Language: Английский

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Radical C–H Sulfonation of Arenes: Its Applications on Bioactive and DNA-Encoded Molecules

Organic Letters, Journal Year: 2022, Volume and Issue: 24(43), P. 7961 - 7966

Published: Oct. 24, 2022

The photocatalyst-free electron donor–acceptor (EDA) complex photochemistry was deemed to expand the potential of photodriven radical chemistry. Here, we report a cross-coupling reaction thianthrenium salt functionalized arenes and sodium sulfinates via photopromoted single transfer (SET) process an EDA complex. A series biarylsulfones were obtained with high site-selectivity reactivity. This mild practical could be applied on bioactive DNA-encoded molecules.

Language: Английский

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In-solution direct oxidative coupling for the integration of sulfur/selenium into DNA-encoded chemical libraries

Chemical Science, Journal Year: 2022, Volume and Issue: 13(9), P. 2604 - 2613

Published: Jan. 1, 2022

DNA-compatible direct oxidative coupling using various sulfur/selenium sources has been achieved, featuring pre-functionalization-free substrates and transition metal-free condition.

Language: Английский

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Antimony salt-promoted cyclization facilitating on-DNA syntheses of dihydroquinazolinone derivatives and its applications

Chinese Chemical Letters, Journal Year: 2023, Volume and Issue: 34(8), P. 108132 - 108132

Published: Jan. 9, 2023

Language: Английский

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Visible Light-Promoted Divergent Benzoheterocyclization from Aldehydes for DNA-Encoded Chemical Libraries

Organic Letters, Journal Year: 2022, Volume and Issue: 24(17), P. 3291 - 3296

Published: April 25, 2022

Benzoheterocyclics have been widely adopted as drug-like core scaffolds that can be incorporated into DNA-encoded chemical library technology for high-throughput hit discovery. Here, we present a visible light-promoted divergent synthesis of on-DNA benzoheterocycles from aldehydes. Four types DNA-conjugated benzoheterocyclics were obtained under mild conditions with broad substrate scope. A cross scope study, together enzymatic ligation and subsequent diversifications, conducted, demonstrating the feasibility this approach in construction.

Language: Английский

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DNA-Compatible Diversification of Indole π-Activated Alcohols via a Direct Dehydrative Coupling Strategy

Organic Letters, Journal Year: 2022, Volume and Issue: 24(4), P. 1022 - 1026

Published: Jan. 20, 2022

Indole-based diversification is highly desired in the DNA-encoded chemical library construction. Herein, we present a general strategy for on-DNA synthesis of diverse C3-functionalized indole derivatives via π-activated alcohol formation followed by direct dehydrative coupling. Highly efficient bond linkages C–C, C–N, and C–S were achieved to fuse building blocks that are widely commercially available. DNA-encoding compatibility method has been further demonstrated pave an avenue application constructing indole-focused three-dimensional libraries.

Language: Английский

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Iodoarene Activation: Take a Leap Forward toward Green and Sustainable Transformations

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Constructing chemical bonds under green sustainable conditions has drawn attention from environmental and economic perspectives. The dissociation of (hetero)aryl-halide is a crucial step most arylations affording (hetero)arene derivatives. Herein, we summarize the (hetero)aryl halides activation enabling direct (hetero)arylation trapping reagents construction highly functionalized (hetero)arenes benign conditions. strategies for aryl iodides are classified into (a) hypervalent iodoarene followed by functionalization thermal/photochemical conditions, (b) aryl-I bond in presence bases with/without organic catalysts promoters, (c) photoinduced presence/absence organophotocatalysts, (d) electrochemical direct/indirect electrolysis mediated organocatalysts mediators acting as electron shuttles, (e) electrophotochemical redox-active organocatalysts. These modes result exhibiting diverse reactivity formal cations/radicals/anions aryne precursors. coupling these reactive intermediates with leads to facile selective formation C-C C-heteroatom bonds. ecofriendly, inexpensive, functional group-tolerant offer alternatives transition metal-based catalysis.

Language: Английский

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Metal‐Free and Open‐Air Arylation Reactions of Diaryliodonium Salts for DNA‐Encoded Library Synthesis

Advanced Science, Journal Year: 2022, Volume and Issue: 9(26)

Published: July 19, 2022

Abstract A successful DNA‐encoded library (DEL) will consist of diverse skeletons and cover chemical space as comprehensive possible to fully realize its potential in drug discovery biology. However, the lack versatile on‐DNA arylation methods for phenols that are less nucleophilic reactive poses a great hurdle DEL include diaryl ether, privileged chemotype pharmaceuticals natural products. This work describes use “substrate activation” approach address DNA‐conjugated phenols. Diaryliodonium salt, highly electrophilic reagent, is employed Ar + sources ensure selective oximes with both high yields DNA fidelity. Notably, new reaction can be applied late‐stage modification peptides containing tyrosine side‐chain synthesize DNA‐tagged analogues existing molecules such sorafenib, known pan‐kinase inhibitor. The diaryliodonium salts chemistry affords greater flexibility design synthesis.

Language: Английский

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