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. The DEF-ring terpenoid fragment of terpendole E, has been synthesized in 15 steps starting from farnesyl acetate, employing radical cyclization (DE-ring formation) and stereoselective cyclization of an epoxyalcohol (F-ring formation). Cell-based assays showed that the right-hand DEF-ring fragment is inactive in cell growth and cell cycle progression of human cancer cell lines.