Studies towards the total synthesis of ginkgolide B Pol Hernández-Lladó, Kilian Garrec, Jonathan W. Burton University of Oxford, UK
Ginkgolide B is a highly oxygenated diterpene with interesting neuroprotective properties. It is a potent platelet- activating factor (PAF) receptor antagonist that has shown potential for the treatment of Alzheimer’s disease, dementia, and ischemia. 1 It contains a rare tert -butyl group, six heavily functionalised five-membered rings (A–F), and 11 chiral centres. Its complexity and therapeutic properties make ginkgolide B an attractive target for total synthesis, which has only been achieved by Corey in 1988 2–4 and Crimmins in 2000. 5 Our approach towards ginkgolide B is based on a malonyl radical cascade; this enabled the synthesis of tricycle II from butenolide I with excellent diastereoselectivity. A two-step sequence involving alkene cleavage and α -hydroxylation was then used to construct ring E and deliver tetracycle III . Current work is focused on the conversion of tetracycle III into pentacycle IV , an intermediate in Corey’s total synthesis. 2–4 We envisage building ring F through decarboxylation, enolate alkylation, and directed reduction. This presentation will cover the synthesis of butenolide I , the development of the malonyl radical cascade, and our efforts towards Corey’s pentacycle IV .
References 1. Maclennan, K. M.; Darlington, C. L.; Smith, P. F., Prog. Neurobiol. 2002 , 67, 235–257. 2. Corey, E. J.; Kang, M. C.; Desai, M. C.; Ghosh, A. K.; Houpis, I. N., J. Am. Chem. Soc. 1988 , 110 (2), 649-651. 3. Corey, E. J., Chem. Soc. Rev. 1988 , 17 (0), 111-133. 4. Corey, E. J.; Gavai, A. V., Tetrahedron Lett. 1988 , 29 (26), 3201-3204. 5. Crimmins, M. T.; Pace, J. M.; Nantermet, P. G.; Kim-Meade, A. S.; Thomas, J. B.; Watterson, S. 6. Wagman, A. S., J. Am. Chem. Soc. 2000 , 122 (35), 8453-8463.
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