Potential antitumor agents. Synthesis, reactivity, and cytotoxicity of .alpha.-methylene carbonyl compounds

Abstract
.alpha.-Methylene lactones were prepared by a mild, convenient .alpha.-methylenation process using the .alpha.-ethyloxalyl derivatives in nonoptimized yields ranging from 23-90%. The rates of reaction of these and several other lactones with cysteine at pH 7.4 and their KB [human oral epidermoid carcinoma cell] toxicities were measured. These studies showed that the strained trans-fused .alpha.-methylene lactone and the hydroxy-.alpha.-methylene lactones did not react with cysteine with rates comparable to elephantopin. Based on these limited studies, the rate of cysteine addition appears to be relatively insensitive to changes in strain energy and neighboring groups. The rate constant for reaction with cysteine did not correlate with cytotoxicity.