Ginkgolides are naturally occurring compounds that can be extracted from the Ginkgo Biloba tree. Their synthesis remains a significant challenge for organic chemists given their complex structure and their numerous stereocenters (2 adjacent quaternary carbons and up to 12 stereocenters). Both Corey and Crimmins reported the total synthesis of (±)-ginkgolide B in 1988 and 1999 respectively. Corey also published the enantioselective formal synthesis of (±)-ginkgolide B as well as the total synthesis of (±)-ginkgolide A in 1988. However, the total synthesis of Ginkgolide C, the most oxygenated and most complex member of the family, has not yet been published. We report herein the first total synthesis of (±)-ginkgolide C as well as the formal synthesis of (±)-ginkgolide A and (±)-ginkgolide B by intercepting Corey’s intermediate (from his total synthesis of (±)-ginkgolide B). The first key step of our syntheses was the Claisen rearrangement which set the first quaternary carbon. The second key step of the syntheses was a kinetic alkylation which sets the second quaternary carbon. The third key step for our syntheses was an enyne epoxidation which enabled the formation of the E-ring. Starting from the Claisen rearrangement adduct, our target intermediate (towards ginkgolide C) was obtained in 18 steps, after which, (±)-ginkgolide C was synthesized in an additional 6 step (total of 26 linear steps). Starting again from the Claisen rearrangement adduct, Corey’s intermediate (from the total synthesis of (±)-ginkgolide B) was obtained in 15 steps which completed the formal syntheses of (±)-ginkgolide A (in an additional 10 steps) and (±)-ginkgolide B (with 6 additional steps).
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/44058 |
| Date | 15 September 2022 |
| Creators | Hébert, Martin |
| Contributors | Barriault, Louis |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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