Synthetic Studies towards Radicicol through Biomimetic Macrolactonization and Transannular Aromatization Reactions

• DOI: 10.1002/ejoc.201402205
• Publication Date: 2014-06-03T18:42:34Z
• Authors: Rosa Cookson; Christoph Pöverlein; Jennifer Lachs; Anthony G. M. Bar...
• Keywords: 01 natural sciences; 0104 chemical sciences

AbstractStudies towards the total synthesis of the natural product radicicol are described that employ a late‐stage esterification and aromatization by trapping a ketene intermediate. The subsequent biomimetic aromatization of the resultant triketo ester gave highly functionalized resorcylates. Two distinct methods were examined that trap the ketene intermediate through either an intermolecular or intramolecular process. In the first approach, the synthesis of the resorcylate was followed by a ring‐closing metathesis, which gave the macrolactone and protected precursors to monocillin I. In the second approach, an intramolecular ketene trapping was examined as an alternative to close the macrocycle and form the resorcylate macrolactone. These studies showcased a wide range of sensitive functional groups that tolerated the aromatization reaction conditions, which started from the corresponding dioxinone precursors.