Total Synthesis of an Exceptional Brominated 4‐Pyrone Derivative of Algal Origin: An Exercise in Gold Catalysis and Alkyne Metathesis. Issue 12 (25th February 2015)

• Record Type: Journal Article
• Authors: Hoffmeister, Laura; Fukuda, Tsutomu; Pototschnig, Gerit; Fürstner, Alois
• Is Part Of: Chemistry. Volume 21:Issue 12(2015)
• Page Start: 4529
• Page End: 4533
• Publication Date: 2015-02-25
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201500437
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A concise approach to the algal metabolite <bold>1</bold> is described, which also determines the previously unknown stereostructure of this natural product. Compound <bold>1</bold> is distinguished by a rare brominated 4‐pyrone nucleus linked as a ketene–acetal to a polyunsaturated macrocyclic scaffold comprising an extra homoallylic bromide entity. The synthesis of <bold>1</bold> is based on the elaboration and selective functionalization of the linear precursor <bold>23</bold> endowed with no less than six different sites of unsaturation including the highly enolized oxo‐alkanoate function. Key to success was the formation of the 2‐alkoxy‐4‐pyrone ring by a novel gold‐catalyzed transformation which engages only the acetylenic β‐ketoester substructure of <bold>23</bold> but leaves all other π‐bonds untouched. The synthesis was completed by a ring‐closing alkyne metathesis to forge the signature cycloalkyne motif of <bold>1</bold> followed by selective bromination of the ketene–acetal site in the resulting product <bold>27</bold> without touching the skipped diene–yne substructure resident within the macrocyclic tether.</p> </abstract>