手性环丙烷/双内酯衍生物的合成

Synthesis of Chiral Cyclopropane Bis-lactones Derivatives

具有四个新手性中心的螺环 /环丙烷类化合物 4在甲醇 /丙酮 / 5 %HCl反应介质中加热回流 ,可以同时消除两个手性辅基 ,形成半缩醛化合物的混合物 .后者与甲醇发生缩醛化反应 ,生成双甲氧基缩醛混合物 5 .经柱层析分离和重结晶得到手性环丙烷 /双内酯衍生物 ,螺 { 1 溴 4 甲氧基 5 氧杂 6 氧代双环 [3.1.0 ]己烷 2 ,2′ (3′ 亲核氧基 4′ 甲氧基丁内酯 ) } (6 ) ,化学产率 6 0 %～ 84 % ,光学纯度de≥ 98% .经元素分析 ,[α]2 0D ,UV ,IR ,1HNMR ,13 CNMR ,MS以及X 射线四圆衍射测定 ,确认了它们的化学结构、立体化学和绝对构型 .此环丙烷 /双内酯双甲氧基衍生物的合成反应可以为活性官能团的引入。

The functionalized spiro-cyclopropane derivatives containing four stereogenic centers 4 were obtained in good yields with de greater than or equal to 98% via tandem double Michael addition/internal nucleophilic substitution of the novel chiral synthon 1. The compound 4 was undergone stereoselective double alcoholic transformation of the auxiliary groups in the presence of methanol/acetone/5% HCl to afford a acetal mixture 5. After separation though column chromatography and recrystallization, the chiral cyclopropane bis-lactones 6 were obtained in yields of 60% similar to 84% with de greater than or equal to 98%. The novel chiral compounds 6a similar to 6f were identified on the basis of their analytical data and spectroscopic data, such as elementary analysis, UV, IR, H-1 NMR, C-13 NMR, MS, and X-ray crystallography.