Synthesis and antitumor activity of simple vinyl and alpha-methylene-gamma-butyrolactone sulfonate esters and silyl enol ethers.

A number of simple silyl enol ethers and vinyl trifluoromethanesulfonates, a relatively new class of organic compounds capable of undergoing alkylation by a nucleophilic addition-elimination process, were evaluated in the P388 lymphocytic leukemia system. No activity (ILS = 8-22%) was observed in the simple vinyl derivatives. Some activity (ILS = 20-42%) was observed for a series of siloxy and sulfonate (CH3SO2 and CF3SO3) functionalized alpha-methylene lactone systems. The enhanced activity of the functionalized systems over the parent methylene lactone is ascribed to a possible irreversible alkylation by cellular nucleophiles via a nucleophilic addition-elimination process.