Chemo-, regio-, and stereoselective tetrafunctionalization of fluoroalkynes enables divergent synthesis of 5-7-membered azacycles

Chemical Science, Journal Year: 2024, Volume and Issue: 15(30), P. 12026 - 12035

Published: Jan. 1, 2024

A 1,2,3,4-tetrafunctionalization of polyfluoroalkynes for the divergent construction 5-7-membered ( E )-1,2-difluorovinyl azacycles is developed.

Language: Английский

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The expanding reaction toolkit for DNA-encoded libraries

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2021, Volume and Issue: 51, P. 128339 - 128339

Published: Aug. 31, 2021

Over the past decade, DNA-encoded libraries (DELs) have emerged as a leading platform for small molecule drug discovery among pharmaceutical companies, biotech companies and academic hunters alike. This revolutionary technology has tremendous potential that is yet to be fully realized, exploration of therapeutically relevant chemical space fueled by ever-expanding repertoire DNA-compatible reactions used construct libraries. Advances in direct coupling reactions, like photo-catalytic cross couplings, unique cyclizations such formation 1,2,4-oxadiazoles, new functional group transformations are valuable contributions DEL reaction toolkit, indicate where future development efforts should focus order maximize productivity DELs.

Language: Английский

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Multiple-fold C–F bond functionalization for the synthesis of (hetero)cyclic compounds: fluorine as a detachable chemical handle

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(7), P. 2013 - 2055

Published: Jan. 1, 2022

We highlighted the recent advances in field of multiple-fold C–F bond functionalization for synthesis (hetero)cyclic compounds.

Language: Английский

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Hexafluoroisopropanol (HFIP) as a Multifunctional Agent in Gold-Catalyzed Cycloisomerizations and Sequential Transformations

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(13), P. 8845 - 8860

Published: June 20, 2023

Despite the unique position of gold catalysis in contemporary organic synthesis, this area research is notorious for requiring activators and/or additives that enable by generating cationic forms catalysts. Cycloisomerization reactions occupy a significant portion gold-catalyzed reaction space, while they represent diverse family are frequently utilized synthesis. Herein, hexafluoroisopropanol (HFIP) shown to be uniquely simple tool cycloisomerizations, rendering use external obsolete and leading highly active catalytic systems with ppm levels catalyst loading certain cases. HFIP assumes dual role as solvent an activator, operating via dynamic activation Au–Cl bond through hydrogen bonding, which initiates cycle. This special mode can efficient scalable cyclization propargylamides ynoic acids [AuCl(L)] complexes. A thorough screening ancillary ligands counter anions has been performed, establishing methodology alternative elaborate ligand/catalyst design activators. Additionally, concept applied C–C bond-forming cycloisomerization 2H-chromenes sequential or one-pot transformations activated ketoesters, functionalized N-heterocyclic carbene (NHC) precursor salt, compound bearing bioactive indole core, among others. Importantly, mechanistic investigations, including "snapshot" species interest solid state, we were able unambiguously detect key H-bonding interaction between catalyst, shedding light on intermolecular enables catalysis. In cases examined herein, not only excellent but also potent activator valuable synthetic handle when incorporated into functional groups products.

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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Bioinspired Selenium‐Nitrogen Exchange (SeNEx) Click Chemistry Suitable for Nanomole‐Scale Medicinal Chemistry and Bioconjugation

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(15)

Published: Feb. 12, 2024

Abstract Click chemistry is a powerful molecular assembly strategy for rapid functional discovery. The development of click reactions with new connecting linkage great importance expanding the toolbox. We report first selenium‐nitrogen exchange (SeNEx) reaction between benzoselenazolones and terminal alkynes (Se−N to Se−C), which inspired by biochemical SeNEx Ebselen cysteine (Cys) residue Se−S). formed selenoalkyne connection readily elaborated, thus endowing this multidimensional diversity. Besides, modular, predictable, high‐yielding, features fast kinetics (k2≥14.43 M −1 s ), excellent group compatibility, works well at miniaturization (nanomole‐scale), opening up many interesting opportunities organo‐Se synthesis bioconjugation, as exemplified sequential (coupled ruthenium‐catalyzed azide‐alkyne cycloaddition (RuAAC) sulfur‐fluoride (SuFEx)), selenomacrocycle synthesis, nanomole‐scale Se‐containing natural product library DNA‐encoded (DEL), late‐stage peptide modification ligation, multiple functionalization proteins. These results indicated that useful developments, established will serve transformative platform in multidisciplinary fields such synthetic chemistry, material science, chemical biology, medical drug

Language: Английский

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Defluorinative Cyclization of Enamides with Fluoroalkyl Halides Through Two Vicinal C(sp³)─F Bonds Functionalization

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

Abstract Introducing distinctive functional groups to expand the structural diversity and improve intrinsic properties of parent molecules has been an essential pursuit in organic chemistry. By using perfluoroalkyl halide (PFAH) as a nontraditional, readily available, ideal 1,2‐difluoroalkenyl coupling partner, defluorinative cyclization reaction enamides for construction fluoroalkenyl oxazoles is first developed. The selective controllable two‐fold cleavage vicinal C(sp 3 )─F bonds PFAH not only enables introduction specific moiety with ease but also results functionalization two 2 )─H without need metal catalyst, photocatalyst, oxidant, or light. method can be applied late‐stage modification complex molecules, synthesis biological‐relevant oxazole analoges, scale‐up synthesis, which all further highlight real‐world utility this protocol. Mechanistic studies reveal that possibly proceeds through radical perfluoroalkylation, consecutive C─F bond heterolytic cleavage, process. In addition, situ formed may serve hydrogen abstractor.

Language: Английский

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Perfluoroalkyl Editing of Fluoroalkynes: Chemo-, Regio-, and Stereoselective Synthesis of (E)-(2-Amino-fluoroalkenyl)pyrimidines

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

A chemo-, regio-, and stereoselective condensation reaction of perfluoroalkyl alkynes (PFAAs), (CH2O)n, (NH4)2CO3 through the cleavage five inert C(sp3)-F bonds at three distinct carbon sites, thereby establishing an unprecedented platform for synthesizing structurally unique (E)-(2-amino-fluoroalkenyl)pyrimidines, is first developed. Remarkably, this features mild conditions, good compatibility with various functional groups, excellent E-stereoselectivity, late-stage modification complex molecules, scalability, versatile synthetic transformations resulting heterocyclic compounds.

Language: Английский

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Recent advances in transition-metal catalyzed directed C–H functionalization with fluorinated building blocks

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(6), P. 1742 - 1775

Published: Jan. 1, 2022

This review focuses on the advances in transition-metal catalyzed reactions with fluorinated building blocks via directed C–H bond activation for construction of diverse organic molecules an insight into probable mechanistic pathway.

Language: Английский

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Selenylation Chemistry Suitable for On‐Plate Parallel and On‐DNA Library Synthesis Enabling High‐Throughput Medicinal Chemistry

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(35)

Published: May 17, 2022

Abstract Click chemistry is a concept wherein modular synthesis used for rapid functional discovery. To this end, continuous discovery of clickable chemical transformations the pillar to support development field. This report details C3‐H selenylation indole that suitable on‐plate parallel and DNA‐encoded library ( Se DEL) via bioinspired LUMO activation strategy. reaction modular, robust highly site‐selective, it features simple mild system (catalyzed by nonmetallic B(C 6 F 5 ) 3 at room temperature), high yields excellent group compatibility. Using method, 1350 indole‐selenides was synthesized in an efficient practical manner, enabling identification ai as promising compound with nanomolar antiproliferative activity cancer cells situ phenotypic screening. These results indicate great potential new high‐throughput medicinal biology.

Language: Английский

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