Facile and efficient one-pot synthesis of 4β-arylaminopodophyllotoxins: synthesis of DNA topoisomerase II inhibitors (NPF and W-68)

A series of 4β-arylamino-4′-O-demethylepipodophyllotoxins and 4β-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF, W-68 and other DNA topoisomerase II inhibitors 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.