Final Activity Report Summary - OXSPIRO (Synthesis of Naturally Occurring Anticancer Agents by the Oxidative Spirocyclisation of Furans)
Several natural products containing a spiroacetal moiety are known for their pronounced antitumoural properties. The objective of this project was to synthesise such natural products and their analogues in order to carry out bioassays and identify new anticancer agents.
In the course of these two years a novel methodology for the synthesis of spiroacetal enol ether bearing an acetylene side-chain was developed. It allowed us to synthesise two natural products and their analogues via the oxidation of appropriately substituted furan derivatives. Bioassays showed that most of these acetylenic spiroacetal enol ethers exhibited weak antioxidant and antibacterial properties. Their anticancer activity would be evaluated soon after the project completion.
Moreover, we demonstrated that butenolides could be epoxidised and that, under appropriate isomerisation conditions, axial hydroxybutenolides could be obtained as the major product. These results would be used by Jeremy Robertson group for the synthesis of AL-1, a potent antitumoural spiroacetal enol ether.
In the course of these two years a novel methodology for the synthesis of spiroacetal enol ether bearing an acetylene side-chain was developed. It allowed us to synthesise two natural products and their analogues via the oxidation of appropriately substituted furan derivatives. Bioassays showed that most of these acetylenic spiroacetal enol ethers exhibited weak antioxidant and antibacterial properties. Their anticancer activity would be evaluated soon after the project completion.
Moreover, we demonstrated that butenolides could be epoxidised and that, under appropriate isomerisation conditions, axial hydroxybutenolides could be obtained as the major product. These results would be used by Jeremy Robertson group for the synthesis of AL-1, a potent antitumoural spiroacetal enol ether.