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Function‐Oriented and Modular (+/−)‐ cis ‐Pseudoguaianolide Synthesis: Discovery of New Nrf2 Activators and NF‐κB Inhibitors
Author(s) -
Emmetiere Fabien,
Ratnayake Ranjala,
Schares Henry A. M.,
Jones Katherine F. M.,
Bevan–Smith Emily,
Luesch Hendrik,
Harki Daniel A.,
Grenning Alexander J.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202100038
Subject(s) - natural product , total synthesis , function (biology) , acceptor , modular design , combinatorial chemistry , stereochemistry , chemistry , biology , computer science , physics , evolutionary biology , condensed matter physics , operating system
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.