Stereoretentive Nucleophilic Substitution at the Tetrasubstituted Carbon of Galiellalactone

Zilma Escobar, Jakob Nilsson, Ritha Gidlöf, Martin Johansson, Olov Sterner

Research output: Contribution to journalArticlepeer-review


The fungal metabolite galiellalactone (1) was, as its acetate 4, discovered to undergo a substitution reaction with cysteine derivatives. By studying the reaction mechanism and the intermediates formed, and in an effort to expand the chemical diversity of the galiellalactonoids, a mild and general method of preparing ether, thioether, and amine analogues of galiellalactone was developed. The reaction is a formal stereoretentive nucleophilic substitution at an oxygenated tertiary carbon. NMR analysis of the progressing reaction shows that it involves an initial allylic substitution to form a new Michael acceptor, followed by the addition of a second equivalent of the nucleophile to this and, finally, a retro Michael reaction. This restores the original galiellalactone system with a double bond between C-2a and C-3, but with a new substituent at C-7b. As galiellalactone is a promising STAT3 inhibitor, this novel transformation facilitates the semisynthesis of a wide variety of new analogues for structure-activity relationship studies.

Original languageEnglish
Pages (from-to)7704-7710
Number of pages7
JournalJournal of Organic Chemistry
Issue number12
Publication statusPublished - 2020

Subject classification (UKÄ)

  • Organic Chemistry


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