Preparation of 2-Substituted Podophyllotoxin Derivatives

Article abstract of DOI:10.1021/jo00389a020

A series of 2-substituted podophyllotoxin derivatives, including 2-methyl-, 2-chloro-, 2-hydroxy-, and 2-bromopodophyllotoxin, were prepared, in order to determine whether nonenolizable podophyllotoxins had enhanced in vivo activity against P388 and L1210 tumor cells.Significant activity against P388 (T/C 156, 40 mg/kg) was observed for 2-chloropodophyllotoxin; under similar conditions, podophyllotoxin was toxic.The corresponding 2-picro isomers were formed as byproducts in the above reactions and were, when tested, inactive against tumors at similar concentrations.An attempt to prepare 2-fluoropodophyllotoxin by reacting podophyllotoxin 4-O-THP enolate with FClO3 resulted in a violent explosion, causing serious injury.Extreme caution should be taken when reacting enolates with FClO3.