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

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.

SUBMITTER: Emmetiere F

PROVIDER: S-EPMC8195264 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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

Emmetiere Fabien F Ratnayake Ranjala R Schares Henry A M HAM Jones Katherine F M KFM Bevan-Smith Emily E Luesch Hendrik H Harki Daniel A DA Grenning Alexander J AJ

Chemistry (Weinheim an der Bergstrasse, Germany) 20210226 17

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 m ...[more]

PMID: 33502811

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