Studies towards the total synthesis of roseophilin

• Main Author: Carter, Caroline Mercedes
• Published: University of Sussex 2002
• Subjects: 615.329378
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407710

The thesis details our approach to roseophilin, a natural product possessing a unique pentacyclic skeleton, which was recently' isolated from Streptomyces griseoviridis. The introduction includes a review of its impressive anticancer activity and studies as to its mode of action. Previous total and partial syntheses are described and their major achievements highlighted. The retrosynthetic strategy, and the rationale on which it is based, is outlined in the results section. Initial efforts are concentrated on the synthesis of the roseophilin macrotricyclic core. Progress towards this compound is presented, including the synthesis of a key intermediate utilising the diastereoselective Ireland-Claisen rearrangement. Further studies into the final steps of the synthetic route are focused on various model systems. The synthesis of an c -azido-ß-ketosulfide, one of a previously unreported class of compounds, is described. The novel method utilises a Pummerer reaction for formation of the azidosulfide from a sulfoxide. The conclusions summarise the achievements attained and the progress made on the synthetic route to roseophilin. Suggestions for any improvements to the developed route are offered, together with possible strategies for the completion of the synthesis