First Asymmetric Total Synthesis of Penarolide Sulfate A 1

Penarolide sulfate A 1 , with three contiguous stereogenic centers on a macrocyclic skeleton, affords promise as an α‐glucosidase inhibitor. Herein, we describe the first asymmetric total synthesis of this natural product. A stereoselective strategy for rapid assembly of the complete framework of the 30‐membered macrocyclic core is delineated herein. Sequential amidation and intramolecular Sonogashira cross‐coupling reactions were pivotal to the success of our efforts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)