Synthesis of 4,8-bis(4-hydroxy-3-methoxyphenyl )-3,7-dioxabicyclo[3.3.0]octan-2-ones and determination of their relative configuration via long-range proton couplings

Abstract

A short synthesis of the furofuranoid lignan, 4-cis,8-cis-bis(4-hydroxy-3-methoxyphenyl)-3,7dioxabicyclo[3.3.0]octan-2-one (MEL), was accomplished via a simple regioselective hydride reduction of the dilactone parent [4-cis,8-cis-bis(4-hydroxy-3-methoxyphenyl)-3.7-dioxabicyclo[3.3.0]octane- 2,6-dione], followed by deoxygenation of the lactone-lactol intermediate via silane hydride transfer. The 4-trans-8-cis(iso-MEL) and the 4-cis-8-trans(epi-MEL) isomers, and a fourth related compound, featuring a 3-fused 5-membered ring skeleton were additionally formed. All four compounds were fully characterized by use of 1D and 2D NMR techniques. Examination of the long-range coupled proton network by delayed COSY experiments allowed determination of the relative configuration of these 4,8-diaryl-3,7-dioxabicyclo[3.3.0]octan-2-one structures. The pathways followed by these long-range proton couplings and implications of the long-range and vicinal couplings with respect to favoured conformations are discussed.