Progress towards the total synthesis of β-araneosene utilizing an alkoxy-directed diastereoselective radical cyclisation

ORGN 794

Michal S. Hallside,, Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom, Martin Hutchings,, UCB Celltech, 216 Bath Road, Slough, SL1 3WE, United Kingdom, and Jonathan W. Burton,, Chemistry Research Laboratory, Oxford University, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom.
β-Araneosene belongs to the class of dolabellane diterpenoids that exhibit potent cytotoxic and antimicrobial activity. It was first isolated from the terrestrial mold Sordria araneosa and contains the trans-fused 5- and 11-membered rings characteristic of the dolabellanes. Our novel approach for the synthesis of β-araneosene, based on the formation and expansion of a [3.3.0]-bicyclic γ-lactone precursor will be described. The key step involving an alkoxy-directed diastereoselective manganese(III) acetate radical cyclisation will also be discussed.