SYNTHESIS AND ANTITUMOR ACTIVITY OF 4-ALKYLTHIO-4-DEOXY-4’-DEMETHYLEPIPODOPHYLLOTXIN DERIVATIVES

As a continuing part of our study on the chemistry and antitumor activity of podo-phyllotoxin , 11 new C-4 S-substituted poclophyllotoxin derivatives were synthesised and screened invitro against L1210 leukemia and KB cells. Thus, 4′-demethylepipodophyllotoxin was reacted withthiols in the presence of BF₃.Et₂O or trifluroacetic acid to give thioethers. In addition, 4-bromo-4-de-oxy-4′-demethylepipodophyllotoxin, when reacted with thiols, also gave rise to correponding thioether(4-alkylthio-4-deoxy-4′-demethylepipodophyllotoxins). Compounds 10 and 12 have the same activityas etoposide in the inhibition against L1210 leukemia, and compounds g, 10, 12 and 15 also havecomparable activity with etoposide against KB cells.