The synthesis of indanones related to combretastatin A-4 via microwave- assisted Nazarov cyclization of chalcones

Our research groups have a long-standing interest in anticancer agents, especially those derived from natural products. In 1996, as part of a plant-screening program, we identified Scutellaria barbata D. Don ( Labiatae ) as a potential source of anticancer agents. The dried whole plant, readily available from herb wholesalers, is used in traditional Chinese medicine as an anti-inflammatory and antitumour agent. It is a component of Shan Ci Gu soup, a herbal prescription for stomach cancer. Bioassay guided fractionation of the herb extract, using the MTT assay to determine cytotoxicity, revealed the presence of many cytotoxic components. One such fraction had an IC50 (K562) of 10 μg/mL. The fraction was predominantly the simple enone 1 (IC50 60 μM) [1]. Preparation of a library of butenones revealed that those possessing electronwithdrawing groups were the most active [2] The pentafluorophenylbutenone 2 was over 30 times more active than the natural product 1.