(R)-(+)-5-甲基-5-{4-[2-(2-(5-氯吲唑基))乙氧基]苄基}-2,4-噁唑烷二酮的合成及其绝对构型的确定  

Synthesis and Determination of Absolute Configuration of (R)-(+)-5-{4-[2-(5-Chloroindazol-2-yl)ethoxy]benzyl}-5-methyl-2,4-oxazolidinedione

作　　者：李雅潇[1] 马慧勇[1] 林紫云[1] 王经斌[1] 杨世颖[1] 张艳红 吕扬[1] 黄海洪[1] 

机构地区：[1]中国医学科学院中国协和医科大学药物研究所,北京100050 [2]国家新药开发工程技术研究中心,北京102600

出　　处：《有机化学》2009年第8期1254-1258,共5页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.30371672);北京市自然科学基金(No.7042042)资助项目

摘　　要：以(S)-(-)-1-苯乙胺为拆分剂对外消旋的α-羟基酸进行拆分,得到手性α-羟基酯4,再与尿素合环、脱甲基保护,得到关键的手性中间体(R)-(+)-5-甲基-5-(4-羟基苄基)-2,4-噁唑烷二酮(6).将化合物6与甲磺酸酯(8)缩合即得具有全新化学结构的标题化合物9(ee值100%),其结构经1HNMR和HRMS确证.根据拆分盐3的单晶X射线衍射分析结果及由α-羟基酯4与尿素合环生成噁唑烷二酮的反应机理,确定标题化合物9的绝对构型为R.The chiral a-hydroxyester 4 was obtained by acid catalyzed esterification of the corresponding a-hydroxylacid that was resolved by （S）-（-）-1-phenylethylamine. After cyclization and deprotection, the key intermediate （R）-（＋）-5-methyl-5-（4-hydroxybenzyl）-2,4-oxazolidinedione （6） was obtained. The novel title compound 9 was obtained by the condensation of 6 with methanesulfonate 8. The structure of 9 was confirmed by 1H NMR and HRMS techniques, and its absolute configuration was derived from the X-ray diffraction of R enantiomer of 3.

关 键 词：2 4-噁唑烷二酮 化学拆分 单晶X射线衍射 绝对构型 

分 类 号：O626[理学—有机化学]