Towards the total synthesis of vinigrol

Abstract

Virigrol is a unique tricyclic diterpene containing the unprecedented decahydro-1, 5- butanonapathalene framework and with these unusual structural features it also has varied biological activity, making it a challenging synthetic target. Despite various groups working in this area, there has been no total synthesis published to date. The thesis begins by discussing the challenging aspect of the total synthesis, construction of the 8-membered ring. Three distinct strategies exist for the construction of 8-membered carbocyclęs. C-C-bond forming reactions and ring expansion approaches have been utilised in the syntheses towards Vinigrol to date. However neither method has yet yielded a total synthesis. Ring fragmentation has not been exploited in the synthesis of Vinigrol to date and is a useful synthetic tool since smaller ring systems are easier to construct than their medium ring counterparts. It was envisaged that the 8-membered ring could be installed in a masked form as a series of 6-membered rings and thereby avoiding the normal difficulties associated with medium ring synthesis. Scheme 1. The key reaction of the synthesis was an intramolecular Diels Alder reaction. This thesis describes three related strategies which were utilised in order to afford the masked 8-membered ring which would then enable the tricyclic skeleton of Vinigrol to be obtained.