Asymmetric Synthesis and in vivo Biological Inactivity of the Right-Hand Terpenoid Fragment of Terpendole E

Synthesis of the DEF-ring terpenoid fragment of terpendole E, an Eg5 inhibitor, is described. The DE-ring was constructed by a modification of Barrero's radical cyclization. The F-ring tetrahydropyran was then constructed by acid-induced cyclization of an epoxy alcohol, which was prepared by cross-metathesis followed by Shi's epoxidation. Cell-based assays indicated that the DEF-ring fragment is not capable of inhibiting cell growth and cell cycle progression of human cancer cell lines, indicating that the DEF-ring fragment alone is not sufficient for the biological activity.