A new method for the synthesis of the [4,3,1] carbocyclic core of the squalene synthase and farnesyl transferase inhibitor CP-225,917 is developed. The key step relies on the [6+4] cycloaddition between a tropone and a cyclopentadiene. This reaction proceeds with excellent regio- and stereoselectivity and allows rapid and convergent access to the polycyclic core of the molecule. / In the course of this work, it was discovered that the cycloaddition process is significantly accelerated in presence of the catalytic amount of ZnCl2. This is the first example of Lewis acid catalyzed [6+4] tropone cycloaddition. / Introduction of other functional groups towards the synthesis of CP-225,917 skeleton is described. The key to the success of this strategy is a position selective Baeyer-Villiger oxidation on the tricyclic cycloadduct. This reveals functionality which can be used to elaborate the C9 side-chain and incorporate the bridgehead olefin.* / *Please refer to dissertation for diagrams.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.38208 |
| Date | January 2001 |
| Creators | Isakovic, Ljubomir. |
| Contributors | Gleason, James L. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001874434, proquestno: NQ78703, Theses scanned by UMI/ProQuest. |
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