1207434-35-2Relevant academic research and scientific papers
Study of the total synthesis of (-)-exiguolide
Cook, Cyril,Liron, Frederic,Guinchard, Xavier,Roulland, Emmanuel
, p. 6728 - 6742 (2012/09/21)
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.
Total synthesis of (-)-exiguolide
Cook, Cyril,Guinchara, Xavier,Liron, Frederic,Roulland, Emmanuel
, p. 744 - 747 (2011/03/17)
The first total synthesis of the naturally occurring enantiomer of exiguolide ((-)-1) has been completed. This very convergent synthesis features the following as main steps: (I) a Trost's ruthenium-catalyzed ene-yne cross-coupling reaction (this complex transformation allows the challenging control of the C5-C28 double bond geometry along with the stereoselective construction of the tetrahydropyran ring A) and (II) a very efficient one-pot, two-step stereoselective conjugated allyllc alcohol substitution that allowed the control of the C15 stereogenic center.
