Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1030 - 1076

Published: Nov. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Language: Английский

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Reductive Radical-Polar Crossover Enabled Carboxylative Alkylation of Aryl Thianthrenium Salts with CO₂ and Styrenes

Organic Letters, Journal Year: 2024, Volume and Issue: 26(3), P. 728 - 733

Published: Jan. 12, 2024

Carboxylic functionalities are among the pivotal groups in bioactive molecules and synthesis of new lead compounds because their unique character formation hydrogen bonds possibility constructing molecular complexes via amide couplings. We adopt reductive radical-polar crossover strategy to introduce carboxyalkyl into arenes with styrenes CO2 thianthrenium salts. This protocol exhibits excellent potential as a straightforward modular platform for site-selective carboxylative derivation molecules.

Language: Английский

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Dibenzothiophenium Salts: Practical Alternatives to Hypervalent I(III)-Based Reagents

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

ConspectusDuring the past few years, interest among organic synthesis practitioners in use of sulfonium salts has exponentially growth. This can arguably be attributed to a series specific factors: (a) The recent development more direct and efficient protocols for these species, which make reagents wide structural variety easily available multigram scale. (b) recognition that reactivity resembles hypervalent iodine compounds, therefore, they used as effective replacement such species most their applications. (c) Their intrinsic thermal stability tolerance air moisture, clearly surpass I(III)-reagents analogue reactivity, facilitate purification, isolation well-defined storage, safely handling on larger (d) Finally, possibility further functionalize once sulfur-containing platform been incorporated. Specifically, this last synthetic approach is not trivial when working with I(III)-species facilitates access no counterpart I(III) realm.This renewed led improvement already existing transformations well discovery unprecedented ones; particular, by incorporate partners traditional cross-coupling C–H activation steps or combine them modern technologies photocatalysis electrosynthesis. In Account, originally prepared our laboratory will outlined compared I(III)-counterparts. Some are now commercially available, started spread widely across chemistry community, helping speed process identification potentially bioactive products new functionaliced materials. However, challenges still remain. characterized an optimal balance between site-selectivity, showing broader compatibility toward sensitive functional groups need. addition, often makes necessary (sophisticated) catalysts activate latent hidden structures. Although priori one see fact disadvantage, it might actually decisive harvest full potential because surely preparation operational context I(III)-chemistry. If becomes true, may contribute expediting retrosynthetic disconnections that, date, impossible.

Language: Английский

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Synergistic Photoredox and Electrochemical Catalysis in Organic Synthesis and Late‐Stage Functionalizations

ChemCatChem, Journal Year: 2024, Volume and Issue: 16(14)

Published: Feb. 7, 2024

Abstract This review delves into the innovative field of interfacial photoelectrochemical (iPEC) and (PEC) catalysis, dynamic synthesis methodologies that seamlessly integrates electrochemical photoredox catalysis for efficient environmentally friendly reactions. Utilizing minute quantities photocatalysts, visible light becomes a powerful tool, generating transient excited states to catalyze spectrum reactions through single‐electron oxidation or reduction events. The categorizes recent advancements, highlighting applications in organic synthesis, late‐stage modifications, distinctive features methodology. Despite being its early stages, this synergistic approach holds great promise propelling forward, with potential large‐scale diverse functionalizations, including asymmetric bioconjugation strategies biomolecule modifications.

Language: Английский

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Palladium-catalyzed decarboxylation [2 + 2 + 2] annulation approach to chromone-containing polycyclic compounds

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(15), P. 3752 - 3759

Published: Jan. 1, 2023

A variety of chromone-containing polycyclic compounds are efficiently generated via Pd-catalyzed decarboxylation [2 + 2 2] annulation 3-iodochromones, bridged olefins and o-bromobenzoic acids, in which o -bromobenzoic acids were employed as the electrophilic aryl units.

Language: Английский

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Cobalt-Catalyzed Remote Site-Selective Hydroboration of Unactivated Alkenes via Chain-Walking Strategy

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

Published: March 11, 2025

An expedient synthesis of α-aminoboronic acid derivatives via cobalt-catalyzed remote site-selective hydroboration unactivated alkenes is described herein. The strategy characterized by its simplicity, site-selectivity, and wide substrate scope, as both terminal internal could undergo the reaction smoothly, affording corresponding products in good yields. According to mechanism, Co-H generated from Co(acac)2 presence HBpin, which starts chain-walking a series alkene insertion β-H elimination process.

Language: Английский

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Imine induced metal-free C–H arylation of indoles

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(24), P. 6063 - 6069

Published: Jan. 1, 2023

A simple, mild, and metal- extra-auxiliary group-free method for the direct arylation of indole-3-carbaldehydes induced by an in situ generated transient directing group was developed.

Language: Английский

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Self-Catalyzed Sono-Photoinduced Arylation of Quinoxalin-2(1H)-ones with Arylhydrazines

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Herein, the first example of self-catalyzed sono-photoinduced carbon-carbon bond formation was described. Combining advantages phototriggered self-catalysis and ultrasonic catalysis, a wide range 3-arylquinoxalin-2(1

Language: Английский

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Palladium(II)-catalyzed annulation of N-methoxy amides and arynes: computational mechanistic insights and substituents effects

Journal of Molecular Modeling, Journal Year: 2024, Volume and Issue: 30(5)

Published: April 30, 2024

Language: Английский

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Magnesium‐Catalyzed Asymmetric Thia‐Michael Addition to α,β‐Unsaturated Ketones

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(6), P. 1412 - 1421

Published: Jan. 23, 2024

Abstract We demonstrate the application of chiral magnesium complexes in an asymmetric carbon‐sulfur bond‐forming reaction. Enantioselective and cost‐effective methodology under mild condition for thia‐Michael addition, utilizing situ generated dinuclear magnesium‐ProPhenol complex, has been developed. The versatility this protocol is demonstrated with a broad range thiol nucleophiles wide selection enones. Enantioenriched β‐ketosulfides are obtained good to excellent yields moderate enantioselectivity. presented catalytic system exhibits tolerance structurally different substrates while maintaining high This observation aligns proposed mechanism, wherein sulfur atom coordinates catalyst close proximity reaction center.

Language: Английский

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