An alternative diastereospecific approach to (±)-samin and 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane [furanofuran] lignans based on the Ireland–Claisen rearrangement of unsaturated oxa-macrolides

Abstract

Ireland–Claisen rearrangement of the nine-membered macrolide 22 leads stereospecifically to the tetrahydrofurancarboxylate 23, via the boat-like transition state 9. The hydroxy-acid precursor 21c to the macrolide 22 has been prepared by Michael addition of the sodium alkoxide of (Z)-allylic alcohol 20 to methyl acrylate in the presence of dimethyl sulfoxide. Subsequent conversion into the corresponding aldehyde 29, Grignard addition, cleavage of the alkene and acid-catalysed cyclisation gives (±)-sesamin 32. The epimeric ester 33 has been converted into (±)-samin 37 by related functional group manipulations, but excluding the Grignard coupling, and a final isomerisation.