Synthesis of 3-methoxy-9-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5H-benzo[7]annulen-4-ol, a potent antineoplastic benzosuberene derivative for anti-cancer chemotherapy

Benzosuberene 8 is a tubulin polymerization inhibitor that possesses remarkable potency against a variety of cancer cell lines. Herein, an efficient synthetic route for 8 is described featuring a Claisen rearrangement/RCM sequence and a late stage Suzuki coupling as the key steps. By adopting this strategy 8 was synthesized in eight steps in 18% overall yield starting from known compound 18.