Synthesis of Biologically Active Guaianolides with a trans-Annulated Lactone Moiety

The biosynthetic pathways of sesquiterpene lactones are described in conjunction with recent developments in the total syntheses of various biologically active guaianolides. Different strategies towards the 5,7,5‐membered ring system are highlighted. Oxidative diol cleavages, aldol reactions, and intramolecular cyclopropanations were used as key reactions to construct the racemic guaianolide core system. Radical cyclizations, as well as ring closing metathesis, were successfully applied in asymmetric approaches. Biomimetic reactions were also applied as versatile tools for the construction of these highly complex natural products.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) Tricyclic guaianolides, for example, thapsigargins, display a broad biological profile, which has prompted the development of diverse synthetic strategies towards them.