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

ORGN 794

Michal S. Hallside, michal.hallside@chem.ox.ac.uk, Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom, Martin Hutchings, martin.hutchings@ucb-group.com, UCB Celltech, 216 Bath Road, Slough, SL1 3WE, United Kingdom, and Jonathan W. Burton, jonathan.burton@chem.ox.ac.uk, 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.