title: Study of the total synthesis of (-)-exiguolide.
abstract: In this article, we disclose the various routes and strategies we had to explore before finally achieving the total synthesis of (-)-exiguolide ((-)-1). Two first types of approaches were set, both relying on the Trost's domino ene-yne coupling/oxa-Michael reaction that we choose for its ability to control the geometry of the methylacrylate-bearing tetrahydropyrane ring B. In our first approach, we expected to assemble the two main fragments (C14-C21 and C1-C13) by creating the C13-C14 bond through a palladium(0)-catalyzed cross-coupling, but this step failed, unfortunately. In the second approach, which was more linear, we created the C16-C17 bond through condensation of a lithium acetylide on a Weinreb amide, and we assembled the C1-C5 and C6-C21 subunits through Trost's domino ene-yne coupling/oxa-Michael reaction. These two approaches served us to design an ameliorated third strategy, which finally led to the total synthesis of (-)-exiguolide.
authors: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelle, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette, France.
authors: Cyril
authors: C
authors: Cook
authors: Frédéric
authors: F
authors: Liron
authors: Xavier
authors: X
authors: Guinchard
authors: Emmanuel
authors: E
authors: Roulland
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D000577:Amides / Q000737:chemistry; D002384:Catalysis; D008094:Lithium / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000179:Acrylates; D000577:Amides; D018942:Macrolides; C527475:exiguolide; D010165:Palladium; D008094:Lithium; C035956:methyl acrylate