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Abstract A strategy to control the diastereoselectivity of bond formation at a prochiral attached‐ring bridgehead is reported. An unusual stereodivergent Michael reaction relies on basic vs. Lewis acidic conditions and non‐covalent interactions to controlre‐ vs.si‐ facial selectivity en route to fully substituted attached‐rings. This divergency reflects differential engagement of one rotational isomer of the attached‐ring system. The successful synthesis of anerythrosubtarget diastereomer ultimately leads to a short formal synthesis of merrilactone A.
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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.
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- Award ID(s):
- 1844443
- PAR ID:
- 10220729
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 27
- Issue:
- 17
- ISSN:
- 0947-6539
- Format(s):
- Medium: X Size: p. 5564-5571
- Size(s):
- p. 5564-5571
- Sponsoring Org:
- National Science Foundation
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