Facile and efficient one-pot synthesis of 4 beta-arylamino-podophyllotoxins: Synthesis of DNA topoisomerase II inhibitors (NPF and W-68)

A series of 4 beta-arylamino-4'-O-demethylepipodophyllotoxins and 4 beta-ar ylaminoepipodophyllotoxins have been synthesized with significant stereosel ectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF, W-68 and other DNA topoisomerase II i nhibitors are prepared in good to excellent yields by this method and these are active or more active than etoposide in their inhibition of the human DNA topoisomerase II. (C) 2000 Elsevier Science Ltd. All rights reserved.