Formal Total Synthesis of(-)-Apicularen A by a Strategy Based on Ring-Closing Metathesis and Transannular Cyclization

摘要

A formal synthesis of(-)-apicularen A,a potent antitumor agent with unique biological properties,has been completed in a 15-step sequence starting from a known,enantiomencally pure hydroxyepoxide,which was generated by using the Jacobsen hydrolytic-kmetic-resolution methodology.The 12-membered macrocyclic lactone in the target was constructed by ring-closing metathesis,and the trans-tetrahydropyran ring system was created through the transannular etheri-fication of a hydroxyalkene.