Prodrugs of 4′-demethyl-4-deoxypodophyllotoxin: synthesis and evaluation of the antitumor activity

A series of prodrugs of 4'-demethyl-4-deoxypodophyllotoxin (DDPT) including carbamates (3-8), a carbonate (9) and water-soluble amino acid derivatives (10-17) were prepared and tested for their antitumor activity. The carbamate 6 (2-hydroxyethylcarbamoyl-DDPT), carbonate 9 (2-chloroethyloxycarbonyl-DDPT), and most of amino acid prodrugs (12-17) showed enhanced antitumor activity.