Studies toward the total synthesis of (−)-kampanol A: an efficient construction of the ABCD ring system

The optically active tetracyclic ABCD ring system 2 of (−)-kampanol A (1), a novel Ras farnesyltransferase inhibitor from a microorganism, was efficiently synthesized starting from the known ketol 4 as a model study. The synthetic method involves conjugate addition reaction of the Grignard reagent of the bromobenzene derivative 14 to the α-methylene ketone 10 to form the coupling product 15 and phenylselenium-mediated cyclization reaction of the phenol derivative 17 to stereoselectively construct the requisite tetracyclic intermediate 18 as the pivotal steps.