One-Pot Synthesis of Difluorobicyclo[1.1.1]pentanes from α-Allyldiazoacetates

Organic Letters, Год журнала: 2023, Номер 25(28), С. 5214 - 5219

Опубликована: Июль 10, 2023

Rapid access to 2,2-difluorobicylco[1.1.1]pentanes is enabled from an α-allyldiazoacetate precursor in a one-pot process through cyclopropanation afford 3-aryl bicyclo[1.1.0]butane, followed by reaction with difluorocarbene the same flask. The modular synthesis of these diazo compounds affords novel 2,2-difluorobicyclo[1.1.1]pentanes that were inaccessible previously reported methods. reactions chiral 2-arylbicyclo[1.1.0]butanes manner generate altogether different products high asymmetric induction, methylene-difluorocyclobutanes. Larger ring systems including bicyclo[3.1.0]hexanes are also rapidly furnished due nature starting material.

Язык: Английский

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Multicomponent DNA-Compatible Synthesis of an Annelated Benzodiazepine Scaffold for Focused Chemical Libraries

Organic Letters, Год журнала: 2023, Номер 25(4), С. 665 - 670

Опубликована: Янв. 24, 2023

Annelated benzodiazepines are attractive drug-like scaffolds with a broad spectrum of biological activities. Incorporation this heterocyclic core into DNA-encoded chemical libraries (DELs) via multicomponent assembly is highly demanded. Herein, we developed DNA-compatible method to generate the tricyclic benzodiazepine scaffold catalyst-free three-component condensation using range aldehyde, o-phenylenediamine, and diketone sources. With either aldehyde or o-phenylenediamine conjugated DNA tags, functionalized 1,5-benzodiazepine were efficiently forged, expanding space diazepine-centered DEL.

Язык: Английский

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Better Together: Catalyzing Innovation in Organic Synthesis via Academic-Industrial Consortia

Organic Letters, Год журнала: 2024, Номер 26(14), С. 2677 - 2681

Опубликована: Янв. 29, 2024

ADVERTISEMENT RETURN TO ISSUEPREVEditorialNEXTBetter Together: Catalyzing Innovation in Organic Synthesis via Academic-Industrial ConsortiaJesús AlcázarJesús AlcázarGlobal Discovery Chemistry, Johnson & Innovative Medicine, Janssen-Cilag, S. A., Jarama 75 A, 45007 Toledo, SpainMore by Jesús Alcázarhttps://orcid.org/0000-0002-2726-196X, Edward A. AndersonEdward AndersonChemistry Research Laboratory, Department of University Oxford, 12 Mansfield Road, Oxford OX1 3TA, United KingdomMore Andersonhttps://orcid.org/0000-0002-4149-0494, Huw M. L. DaviesHuw DaviesDepartment Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, StatesMore Davieshttps://orcid.org/0000-0001-6254-9398, Rio FebrianRio FebrianDepartment Febrian, Christopher B. KellyChristopher KellyDiscovery Process Research, 1400 McKean Spring House, Pennsylvania 19477, Kellyhttps://orcid.org/0000-0002-5530-8606, Timothy NoëlTimothy NoëlFlow Chemistry Group, van't Hoff Institute for Molecular Sciences (HIMS), Amsterdam, 1098 XH The NetherlandsMore Noëlhttps://orcid.org/0000-0002-3107-6927, Eric VoightEric VoightDiscovery AbbVie, Inc., 1 N Waukegan Rd, North Chicago, Illinois 60064, Voighthttps://orcid.org/0000-0002-9542-5356, Cayetana Zarate*Cayetana ZarateChemical R&D, Janssen-Cilag AG, Hochstrasse 201, 8200 Schaffhausen, Switzerland*Email: [email protected]More Zaratehttps://orcid.org/0000-0002-4002-6147, and Eli Zysman-ColmanEli Zysman-ColmanOrganic Semiconductor Centre, EaStCHEM School St Andrews, Haugh, KY16 9ST U.K.More Zysman-Colmanhttps://orcid.org/0000-0001-7183-6022Cite this: Org. Lett. 2024, 26, 14, 2677–2681Publication Date (Web):January 29, 2024Publication History Received17 January 2024Published online29 inissue April 2024https://pubs.acs.org/doi/10.1021/acs.orglett.4c00192https://doi.org/10.1021/acs.orglett.4c00192editorialACS PublicationsCopyright © Published 2024 American Chemical Society. This publication is available under these Terms Use. Request reuse permissions free to access through this site. Learn MoreArticle Views5626Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (2 MB) Get e-Alertsclose e-Alerts

Язык: Английский

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DNA-Compatible Cyclization Reaction to Access 1,3,4-Oxadiazoles and 1,2,4-Triazoles

Organic Letters, Год журнала: 2024, Номер 26(7), С. 1353 - 1357

Опубликована: Фев. 9, 2024

DNA-encoded chemical library (DECL) technology is a commonly employed screening platform in both the pharmaceutical industry and academia. To expand space of DECLs, new robust DNA-compatible reactions are sought after. In particular, cyclization highly valued, as these tend to be atom economical thus may provide lead- drug-like molecules. Herein, we report two methodologies employing DNA-conjugated thiosemicarbazides common precursor, yielding substituted 1,3,4-oxadiazoles 1,2,4-triazoles. These novel feature high conversion efficiency broad substrate scope under mild conditions that do not observably degrade DNA.

Язык: Английский

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Using DNA-encoded libraries of fragments for hit discovery of challenging therapeutic targets

Expert Opinion on Drug Discovery, Год журнала: 2024, Номер 19(6), С. 725 - 740

Опубликована: Май 16, 2024

Introduction The effectiveness of Fragment-based drug design (FBDD) for targeting challenging therapeutic targets has been hindered by two factors: the small library size and complexity fragment-to-hit optimization process. DNA-encoded (DEL) technology offers a compelling robust high-throughput selection approach to potentially address these limitations.

Язык: Английский

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Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations

Nature Synthesis, Год журнала: 2024, Номер 3(12), С. 1538 - 1549

Опубликована: Сен. 5, 2024

Язык: Английский

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Synthesis of Functionalized Triazoles on DNA via Azide-Acetonitrile “Click” Reaction

Organic Letters, Год журнала: 2023, Номер 25(46), С. 8326 - 8331

Опубликована: Ноя. 9, 2023

Triazoles are privileged structural motifs that embedded in a number of molecules with interesting biological activities. In this work, we developed practical and general synthetic strategy to construct medicinally important 5-amino-1,2,3-triazole moiety on DNA by coupling DNA-conjugated azides monosubstituted acetonitriles via azide-acetonitrile "click" reaction. Under mild reaction conditions, displayed broad substrate scope. Most substrates gave moderate-to-excellent conversions. Thus, DNA-compatible could be employed DNA-encoded library (DEL) construction potentially expand the chemical space libraries.

Язык: Английский

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Photocatalyzed Dual Strain Release of [1.1.1]Propellane with Diazo Compounds

ACS Catalysis, Год журнала: 2024, Номер 14(8), С. 5481 - 5490

Опубликована: Март 28, 2024

In recent years, many methods for the synthesis of bicyclo[1.1.1]pentane (BCP) scaffolds have been successfully established owing to their remarkable potent bioactive properties. These BCP are typically derived from single strain release [1.1.1]propellane. However, approaches dual [1.1.1]propellane remain elusive, despite potential create innovative opportunities useful propellane derivatization. this report, we present herein an efficient method photocatalyzed with diazo compounds. Many compounds, including those natural products, such as (+)-borneol, estrone, vitamin E, L-menthol, metronidazole, and geraniol, can be applied these transformations. Importantly, allows cleavage formation multiple C–C bonds in a tandem intersystem crossing (ISC)/radical ring-opening/radical–radical recombination process, products easily transformed into synthetically challenging spiro [2.3] [3.4]

Язык: Английский

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sp³‐Rich Heterocycle Synthesis on DNA: Application to DNA‐Encoded Library Production

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(12)

Опубликована: Фев. 8, 2024

DNA encoded library (DEL) synthesis represents a convenient means to produce, annotate and store large collections of compounds in small volume. While DELs are well suited for drug discovery campaigns, the chemistry used their production must be compatible with tag, which can limit compound class accessibility. As result, most heavily populated peptidomimetic sp

Язык: Английский

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Silacarboxylic Acid Mediated Photoredox Z-Stereoselective Fluoroalkylation of Alkynes

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(13), С. 3700 - 3709

Опубликована: Янв. 1, 2024

The photoredox-catalyzed fluoroalkylation of alkynes has been developed with silacarboxylic acid as an easily accessible, safe, and highly stable novel halogen-atom transfer mediator.

Язык: Английский

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