Function-Oriented and Modular (+/−)-cis-Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF-κB Inhibitors

Fabien Emmetiere; Ranjala Ratnayake; Henry A.M. Schares; Katherine F.M. Jones; Emily Bevan–Smith; Hendrik Luesch; Daniel A. Harki; Alexander J. Grenning

doi:10.1002/chem.202100038

Function-Oriented and Modular (+/−)-cis-Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF-κB Inhibitors

Fabien Emmetiere, Ranjala Ratnayake, Henry A.M. Schares, Katherine F.M. Jones, Emily Bevan–Smith, Hendrik Luesch, Daniel A. Harki, Alexander J. Grenning

Medicinal Chemistry

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3 Scopus citations

Abstract

Described herein is a function-oriented synthesis route and biological evaluation of pseudoguaianolide analogues. The 10-step synthetic route developed retains the topological complexity of the natural product, installs functional handles for late-stage diversification, and forges the key bioactive Michael acceptors early in the synthesis. The analogues were found to be low-micromolar Nrf2 activators and micromolar NF-κB inhibitors and dependent on the local environment of the Michael acceptor moieties.

Original language	English (US)
Pages (from-to)	5564-5571
Number of pages	8
Journal	Chemistry - A European Journal
Volume	27
Issue number	17
DOIs	https://doi.org/10.1002/chem.202100038
State	Published - Mar 22 2021

Bibliographical note

Publisher Copyright:
© 2021 Wiley-VCH GmbH

Keywords

NF-κB inhibitors
Nrf2 activators
enyne metathesis
modular synthesis
pseudoguaianolides

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abstract = "Described herein is a function-oriented synthesis route and biological evaluation of pseudoguaianolide analogues. The 10-step synthetic route developed retains the topological complexity of the natural product, installs functional handles for late-stage diversification, and forges the key bioactive Michael acceptors early in the synthesis. The analogues were found to be low-micromolar Nrf2 activators and micromolar NF-κB inhibitors and dependent on the local environment of the Michael acceptor moieties.",

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AU - Schares, Henry A.M.

AU - Jones, Katherine F.M.

AU - Bevan–Smith, Emily

AU - Luesch, Hendrik

AU - Harki, Daniel A.

AU - Grenning, Alexander J.

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KW - modular synthesis

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Function-Oriented and Modular (+/−)-cis-Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF-κB Inhibitors

Abstract

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Keywords

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