Cassady J M, Byrn S R, Stamos I K, Evans S M, McKenzie A
J Med Chem. 1978 Aug;21(8):815-9. doi: 10.1021/jm00206a020.
The alpha-methylene lactones 9, 12, 21, and 24 were prepared by a mild, convenient alpha-methylenation process using the alpha-ethyloxalyl derivatives in nonoptimized yields ranging from 23 to 90%. The rates of reaction of these and several other lactones with cysteine at pH 7.4 and their KB toxicities were measured. These studies showed that neither the strained trans-fused alpha-methylene lactone 12 nor the hydroxy-alpha-methylene lactones 5 and 6 reacted 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. In addition, the rate constant for reaction with cysteine did not correlate with cytotoxicity.
通过使用α-乙基草酰衍生物，采用温和、简便的α-亚甲基化方法制备了α-亚甲基内酯9、12、21和24，产率未优化，范围为23%至90%。测定了这些内酯以及其他几种内酯在pH 7.4条件下与半胱氨酸的反应速率及其KB毒性。这些研究表明，无论是具有张力的反式稠合α-亚甲基内酯12，还是羟基-α-亚甲基内酯5和6，与半胱氨酸反应的速率都无法与土木香内酯相媲美。基于这些有限的研究，半胱氨酸加成速率似乎对张力能和相邻基团的变化相对不敏感。此外，与半胱氨酸反应的速率常数与细胞毒性无关。
