Recognition in the Domain of Molecular Chirality: From Noncovalent Interactions to Separation of Enantiomers

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(16), P. 13235 - 13400

Published: Aug. 2, 2022

It is not a coincidence that both chirality and noncovalent interactions are ubiquitous in nature synthetic molecular systems. Noncovalent interactivity between chiral molecules underlies enantioselective recognition as fundamental phenomenon regulating life human activities. Thus, represent the narrative thread of fascinating story which goes across several disciplines medical, chemical, physical, biological, other natural sciences. This review has been conceived with awareness modern attitude toward its consequences needs to be founded on multidisciplinary approaches disclose basis essential phenomena domain With primary aim discussing this topic an integrated way, comprehensive pool rational systematic information provided, concerns fundamentals chirality, description interactions, their implications processes occurring different contexts. A specific focus devoted enantioselection chromatography electromigration techniques because unique feature "multistep" processes. second motivation for writing make clear statement about state art, tools we have at our disposal, what still missing fully understand mechanisms underlying recognition.

Language: Английский

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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 6, 2023

Abstract Undruggable proteins are a class of that often characterized by large, complex structures or functions difficult to interfere with using conventional drug design strategies. Targeting such undruggable targets has been considered also great opportunity for treatment human diseases and attracted substantial efforts in the field medicine. Therefore, this review, we focus on recent development discovery targeting “undruggable” their application clinic. To make review well organized, discuss strategies proteins, including covalent regulation, allosteric inhibition, protein–protein/DNA interaction targeted nucleic acid-based approach, immunotherapy others.

Language: Английский

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Progress in organocatalytic asymmetric (4+3) cycloadditions for the enantioselective construction of seven-membered rings

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(4), P. 966 - 992

Published: Feb. 15, 2023

Language: Английский

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Enantioselective Transformations in the Synthesis of Therapeutic Agents

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(15), P. 9397 - 9446

Published: July 7, 2023

The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, efficient synthesis enantiopure pharmaceuticals or their synthetic intermediates poses profound challenge to medicinal process chemists. significant advancement in asymmetric catalysis provided an effective reliable solution this challenge. successful application transition metal catalysis, organocatalysis, biocatalysis pharmaceutical industries promoted discovery by precise preparation enantio-enriched therapeutic agents, facilitated industrial production active ingredient economic environmentally friendly fashion. present review summarizes most recent applications (2008–2022) industry ranging from scales pilot levels. It also showcases latest achievements trends agents with state art technologies catalysis.

Language: Английский

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Advances in organocatalytic asymmetric [3 + 3] cycloadditions: synthesis of chiral six-membered (hetero)cyclic compounds

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(19), P. 5573 - 5604

Published: Jan. 1, 2024

This review has summarized the development of organocatalytic asymmetric [3 + 3] cycloadditions and given insights into remaining challenges to promote future this field.

Language: Английский

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Continuous flow asymmetric synthesis of chiral active pharmaceutical ingredients and their advanced intermediates

Green Chemistry, Journal Year: 2021, Volume and Issue: 23(17), P. 6117 - 6138

Published: Jan. 1, 2021

Catalytic enantioselective transformations provide well-established and direct access to stereogenic synthons that are broadly distributed among active pharmaceutical ingredients (APIs). These reactions have been demonstrated benefit considerably from the merits of continuous processing microreactor technology. Over past few years, flow catalysis has grown into a mature field found diverse applications in asymmetric synthesis pharmaceutically substances. The present review therefore surveys chemistry-based approaches for chiral APIs their advanced intermediates, covering utilization biocatalysis, organometallic metal-free organocatalysis introduce asymmetry continuously operated systems. Single-step processes, interrupted multistep syntheses, combined batch/flow processes uninterrupted one-flow syntheses discussed herein.

Language: Английский

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Recent developments in next generation (S)-proline-derived chiral organocatalysts

Tetrahedron, Journal Year: 2021, Volume and Issue: 88, P. 132143 - 132143

Published: April 20, 2021

Language: Английский

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Organocatalysis emerging as a technology

Pure and Applied Chemistry, Journal Year: 2021, Volume and Issue: 93(12), P. 1371 - 1381

Published: July 13, 2021

Abstract During the last 20 years, organocatalysis has significantly advanced as a field. Thanks to contributions from hundreds of groups and companies around world, area risen few mechanistically ill-defined niche reactions, one most vibrant innovative fields in chemistry, providing several well-defined generic activation modes for selective catalysis. Organocatalysis is also on rise industrial settings, especially production enantiomers, which are use fine pharma, crop-protection, fragrance chemistry. Here we will look at some specific elements that think particularly attractive contribute this successful development.

Language: Английский

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Remote C(sp³)−H Acylation of Amides and Cascade Cyclization via N‐Heterocyclic Carbene Organocatalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(15)

Published: Feb. 3, 2022

Abstract The direct functionalization of inert C(sp 3 )−H bonds under environmentally benign catalytic conditions remains a challenging task in synthetic chemistry. Here, we report an organocatalytic remote acylation amides and cascade cyclization through radical‐mediated 1,5‐hydrogen atom transfer mechanism using N‐heterocyclic carbene as the catalyst. Notably, diversity nitrogen‐containing substrates, including simple linear aliphatic carbamates ortho ‐alkyl benzamides, can be successfully applied to this system. With established protocol, over 120 examples functionalized δ‐amino ketones isoquinolinones with diverse substituents were easily synthesized up 99 % yield mild conditions. robustness generality strategy further highlighted by successful unactivated late‐stage modification pharmaceutical molecules. Then, asymmetric control radical reaction was attempted proven feasible newly designed chiral thiazolium catalyst, moderate enantioselectivity obtained at current stage. Preliminary mechanistic investigations several reactions, KIE experiments, computational studies shed light on mechanism.

Language: Английский

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Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Sept. 14, 2022

Abstract Regulated cell death (RCD) is a critical and active process that controlled by specific signal transduction pathways can be regulated genetic signals or drug interventions. Meanwhile, RCD closely related to the occurrence therapy of multiple human cancers. Generally, subroutines are key tumorigenesis, which contributed our better understanding cancer pathogenesis therapeutics. Indole alkaloids derived from natural sources well defined for their outstanding biological pharmacological properties, like vincristine, vinblastine, staurosporine, indirubin, 3,3′-diindolylmethane, currently used in clinic under clinical assessment. Moreover, such compounds play significant role discovering novel anticancer agents. Thus, here we systemically summarized recent advances indole as agents targeting different subroutines, including classical apoptosis autophagic signaling crucial other ferroptosis, mitotic catastrophe, necroptosis, anoikis, cancer. further discussed cross talk between mediated combined strategies (e.g., 3,10-dibromofascaplysin with olaparib) exhibit therapeutic potential against various cancers regulating subroutines. In short, information provided this review on regulation targets expected beneficial design molecules greater thereby facilitating development new therapy. Graphic abstract

Language: Английский

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