Synthesis and cytotoxic evaluation of C-9 oxidized podophyllotoxin derivatives

A series of cyclolignans oxidized at C-9 position has been prepared from the cytotoxic and selective podophyllic aldehyde. The functionalities considered at C-9 were carboxylic acids and several derivatives such as anhydrides, esters, nitriles or amides. A series of podophyllotoxin and podophyllic aldehyde derivatives, lacking the lactone ring and oxidized at C-9 position, has been prepared. The functionalities considered at C-9 were carboxylic acids and several derivatives such as esters, amides, nitriles or anhydrides. The synthesized compounds were cytotoxic at the micromolar level, though less potent and selective than the parent compounds, revealing the influence of the C-9 electrophilic character on the potency and selectivity of these cyclolignans.