Towards the enantioselective synthesis of (−)-euonyminol – preparation of a fully functionalised lower-rim model

Abstract

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 (−)-euonyminol (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).