Synthesis and biological evaluation of carbon-substituted C-4 derivatives of podophyllotoxin

Abstract

Several C-4 carbon-substituted analogues of podophyllotoxin, 1, were prepared by treatment of 1 with allyltrimethylsilane or trimethylsilylcyanide in the presence of boron trifluoride etherate. Alternatively, carbon substituents were introduced via additions to the carbobenzyloxy-protected C-4′-dimethylated podophyllotoxone. These 4′-dimethylated derivatives showed promising in vitro antitumour activity and were equally active against human colon cell line HT116 and two multidrug resistant cell lines. The alcohol 6 was evaluated in vivo but was found to be inactive. Key words: podophyllotoxin analogues, podophyllotox-4-one, C4 carbon substituted podophyllotoxins.