2019 Volume 77 Issue 5 Pages 452-462
This account describes convergent total synthesis of bioactive cardenolides, 19-hydroxysarmentogenin-3-O-α-ʟ-rhamnoside, trewianin and ouabagenin. The highly oxygenated structures of the target cardenolides were assembled by applying a convergent and unified strategy. The AB-ring and the D-ring were coupled via formation of the acetal tether and 6-exo radical cyclization. The subsequent aldol reaction enabled the introduction of the three new stereocenters, giving rise to the steroid framework with the cis-fused CD-ring. Attachment of the C17-butenolide by Stille coupling and installation of the ʟ-rhamnose completed the total syntheses of the target cardenolides. The structure-activity relationship study using the synthesized natural and unnatural cardenolides demonstrated the biological importance of the hydroxy groups, the monosaccharide moiety, and the butenolide substructure.
