Jan 2013 – Full Paper in Org. Biomol. Chem. Published

This paper describes our work towards the enantioselective synthesis of euonyminol, the core component of the anti-HIV natural product hypoglaunine B.

Matthew J. Webber, Sarah A. Warren, Damian M. Grainger, Matthew Weston, Stacy Clark, Steven J. Woodhead, Lyn Powell, Stephen Stokes, Alexander Alanine, Jeffrey P. Stonehouse, Christopher S. Frampton, Andrew J. P. White and Alan C. Spivey ‘Towards the enantioselective synthesis of (-)-euonyminol - preparation of a fully functionalised lower-rim model', Org. Biomol. Chem. 2013, 2514 (LINK).

The development of a stereoselective total synthesis of β-dihydroagarofuran 4 is described. This compound contains the same oxygenation pattern on its ‘lower-rim’ as found in the natural sesquiterpene (−)-euonymino (1) and it is expected that the route described should be applicable to the synthesis of that complex natural product. (−)-Euonyminol is found as the core scaffold of a series of complex macrodilactone sesquiterpenoids isolated from the Celastraceae which possess interesting biological activities (e.g. anti-HIV activity). The synthetic route builds upon an epoxidative asymmetric desymmetrisation of meso-diallylic alcohol 10 that we have reported previously. It features a lactate Ireland–Claisen rearrangement to establish the quaternary stereocentre at C11 (27 → 28a) and an unusual dealkylative intramolecular epoxide-opening by the C11 methyl ether to establish the tetrahydrofuranyl C-ring of the β-dihydroagarofuran skeleton (35 → 36).