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有机化学
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有机化学 ›› 2009, Vol. 29 ›› Issue (08): 1254-1258. 上一篇    下一篇

研究论文

(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

李雅潇a; 马慧勇a ; 林紫云a; 王经斌a; 杨世颖a ;
张艳红b ; 吕 扬a ; 黄海洪*,a
  

  1. (a中国医学科学院中国协和医科大学药物研究所 北京 100050)
    (b国家新药开发工程技术研究中心 北京 102600)
  • 收稿日期:2009-03-17 修回日期:2009-04-27 发布日期:2009-08-30
  • 通讯作者: 黄海洪

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

Li, Yaxiaoa; Ma, Huiyonga ; Lin, Ziyuna ; Wang, Jingbina; Yang, Shiyinga;
Zhang, Yanhongb ; Lü, Yanga; Huang, Haihong*,a
  

  1. (a Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050) (b National Engineering Research Center for the Development of New Drugs, Beijing 102600)
  • Received:2009-03-17 Revised:2009-04-27 Published:2009-08-30
  • Contact: Huang, Haihong

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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1 H NMR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.

关键词: 2,4-噁唑烷二酮, 化学拆分, 绝对构型, 单晶X射线衍射

The chiral α-hydroxyester 4 was obtained by acid catalyzed esterification of the corresponding α-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.

Key words: chemical resolution, single-crystal X-ray diffraction, absolute configuration, 2,4-oxazolidinedione