Synthetic studies of kampanols, novel p21ras farnesyltransferase inhibitors: an efficient synthesis of the tetracyclic ABCD ring system of kampanols

An enantioselective synthesis of the tetracyclic ABCD ring system () of kampanols, novel Ras farnesyltransferase inhibitors from a microorganism, was efficiently achieved for the first time starting from the known trans-decalone derivative . The synthetic method involves the following two key steps: (i) a conjugate addition reaction between the α-methylene ketone and the Grignard reagent () of the ortho-disubstituted bromobenzene derivative to deliver the coupling product with stereoselectivity at the C9 position and (ii) a phenylselenium-mediated cyclization reaction of the phenol derivative to stereoselectively construct the requisite tetracyclic intermediate possessing the cis-fused connectivity of the B/C rings.