Geometric Isomerisation of Bifunctional Alkenyl Fluoride Linchpins: Stereodivergence in Amide and Polyene Bioisostere Synthesis

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Max Wienhold
  • Byeongseok Kweon
  • Calum McLaughlin
  • Matthias Schmitz
  • Till JB Zaehringer
  • Constantin G Daniliuc
  • Christoph Kerzig
  • Ryan Gilmour
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000993907100001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1002/anie.202304150
eISSN
1521-3773
Externe Identifier
  • Clarivate Analytics Document Solution ID: H1VI5
  • PubMed Identifier: 37144434
ISSN
1433-7851
Zeitschrift
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Schlüsselwörter
  • Bioisosteres
  • Catalysis
  • Fluorine
  • Isomerisation
  • Polyenes
Datum der Veröffentlichung
2023
Status
Published
Titel
Geometric Isomerisation of Bifunctional Alkenyl Fluoride Linchpins: Stereodivergence in Amide and Polyene Bioisostere Synthesis
Sub types
  • Article
  • Early Access

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:title>Abstract</jats:title><jats:p>Amide groups are pervasive across the chemical space continuum, where their structural and pharmacological importance, juxtaposed with the hydrolytic vulnerabilities, continues to fuel bioisostere development. Alkenyl fluorides have a venerable history as effective mimics (Ψ[CF=CH]) owing to the planarity of the motif and intrinsic polarity of the C(sp<jats:sup>2</jats:sup>)−F bond. However, emulating the <jats:italic>s‐cis</jats:italic> to the <jats:italic>s‐trans</jats:italic> isomerisation of a peptide bond with fluoro‐alkene surrogates remains challenging, and current synthetic solutions only enable access to a single configuration. Through the design of an ambiphilic linchpin based on a fluorinated β‐borylacrylate, it has been possible to leverage energy transfer catalysis to affect this unprecedented isomerisation process: this provides geometrically‐programmable building blocks that can be functionalised at either terminus. Irradiation at <jats:italic>λ</jats:italic><jats:sub>max</jats:sub>=402 nm with inexpensive thioxanthone as a photocatalyst enables rapid, effective isomerisation of tri‐ and tetra‐substituted species (up to <jats:italic>E</jats:italic>/<jats:italic>Z</jats:italic> 98 : 2 in 1 h), providing a stereodivergent platform for small molecule amide and polyene isostere discovery. Application of the methodology in target synthesis and initial laser spectroscopic studies are disclosed together with crystallographic analyses of representative products.</jats:p>
Autoren
  • Max Wienhold
  • Byeongseok Kweon
  • Calum McLaughlin
  • Matthias Schmitz
  • Till JB Zähringer
  • Constantin G Daniliuc
  • Christoph Kerzig
  • Ryan Gilmour
DOI
10.1002/anie.202304150
eISSN
1521-3773
ISSN
1433-7851
Ausgabe der Veröffentlichung
27
Zeitschrift
Angewandte Chemie International Edition
Sprache
en
Online publication date
2023
Datum der Veröffentlichung
2023
Status
Published
Herausgeber
Wiley
Herausgeber URL
http://dx.doi.org/10.1002/anie.202304150
Datum der Datenerfassung
2023
Titel
Geometric Isomerisation of Bifunctional Alkenyl Fluoride Linchpins: Stereodivergence in Amide and Polyene Bioisostere Synthesis
Ausgabe der Zeitschrift
62

Datenquelle: Crossref

Abstract
Amide groups are pervasive across the chemical space continuum, where their structural and pharmacological importance, juxtaposed with the hydrolytic vulnerabilities, continues to fuel bioisostere development. Alkenyl fluorides have a venerable history as effective mimics (Ψ[CF=CH]) owing to the planarity of the motif and intrinsic polarity of the C(sp<sup>2</sup> )-F bond. However, emulating the s-cis to the s-trans isomerisation of a peptide bond with fluoro-alkene surrogates remains challenging, and current synthetic solutions only enable access to a single configuration. Through the design of an ambiphilic linchpin based on a fluorinated β-borylacrylate, it has been possible to leverage energy transfer catalysis to affect this unprecedented isomerisation process: this provides geometrically-programmable building blocks that can be functionalised at either terminus. Irradiation at λ<sub>max</sub> =402 nm with inexpensive thioxanthone as a photocatalyst enables rapid, effective isomerisation of tri- and tetra-substituted species (up to E/Z 98 : 2 in 1 h), providing a stereodivergent platform for small molecule amide and polyene isostere discovery. Application of the methodology in target synthesis and initial laser spectroscopic studies are disclosed together with crystallographic analyses of representative products.
Addresses
  • Organisch Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 36, 48149, Münster, Germany.
Autoren
  • Max Wienhold
  • Byeongseok Kweon
  • Calum McLaughlin
  • Matthias Schmitz
  • Till JB Zähringer
  • Constantin G Daniliuc
  • Christoph Kerzig
  • Ryan Gilmour
DOI
10.1002/anie.202304150
eISSN
1521-3773
Externe Identifier
  • PubMed Identifier: 37144434
Funding acknowledgements
  • Johannes Gutenberg-Universität Mainz:
  • Horizon 2020 Framework Programme: 956324
  • Alexander von Humboldt-Stiftung:
  • Westfälische Wilhelms-Universität Münster:
  • Deutsche Bundesstiftung Umwelt: 20022/028
Open access
false
ISSN
1433-7851
Ausgabe der Veröffentlichung
27
Zeitschrift
Angewandte Chemie (International ed. in English)
Sprache
eng
Medium
Print-Electronic
Online publication date
2023
Paginierung
e202304150
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
Geometric Isomerisation of Bifunctional Alkenyl Fluoride Linchpins: Stereodivergence in Amide and Polyene Bioisostere Synthesis.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
62

Datenquelle: Europe PubMed Central

Abstract
Amide groups are pervasive across the chemical space continuum, where their structural and pharmacological importance, juxtaposed with the hydrolytic vulnerabilities, continues to fuel bioisostere development. Alkenyl fluorides have a venerable history as effective mimics (Ψ[CF=CH]) owing to the planarity of the motif and intrinsic polarity of the C(sp2 )-F bond. However, emulating the s-cis to the s-trans isomerisation of a peptide bond with fluoro-alkene surrogates remains challenging, and current synthetic solutions only enable access to a single configuration. Through the design of an ambiphilic linchpin based on a fluorinated β-borylacrylate, it has been possible to leverage energy transfer catalysis to affect this unprecedented isomerisation process: this provides geometrically-programmable building blocks that can be functionalised at either terminus. Irradiation at λmax =402 nm with inexpensive thioxanthone as a photocatalyst enables rapid, effective isomerisation of tri- and tetra-substituted species (up to E/Z 98 : 2 in 1 h), providing a stereodivergent platform for small molecule amide and polyene isostere discovery. Application of the methodology in target synthesis and initial laser spectroscopic studies are disclosed together with crystallographic analyses of representative products.
Autoren
  • Max Wienhold
  • Byeongseok Kweon
  • Calum McLaughlin
  • Matthias Schmitz
  • Till JB Zähringer
  • Constantin G Daniliuc
  • Christoph Kerzig
  • Ryan Gilmour
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37144434
DOI
10.1002/anie.202304150
eISSN
1521-3773
Funding acknowledgements
  • Westfälische Wilhelms-Universität Münster:
  • Alexander von Humboldt-Stiftung:
  • Horizon 2020 Framework Programme: 956324
  • Johannes Gutenberg-Universität Mainz:
  • Deutsche Bundesstiftung Umwelt: 20022/028
Ausgabe der Veröffentlichung
27
Zeitschrift
Angew Chem Int Ed Engl
Schlüsselwörter
  • Bioisosteres
  • Catalysis
  • Fluorine
  • Isomerisation
  • Polyenes
Sprache
eng
Country
Germany
Paginierung
e202304150
Datum der Veröffentlichung
2023
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Geometric Isomerisation of Bifunctional Alkenyl Fluoride Linchpins: Stereodivergence in Amide and Polyene Bioisostere Synthesis.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
62

Datenquelle: PubMed

Beziehungen:
Eigentum von

Werkzeuge