| 不对称亨利反应在(R)-沙美特罗合成中的应用 |
| |
| 引用本文： | 刘 宝,尹 璐,贾 娴,黎星术. 不对称亨利反应在(R)-沙美特罗合成中的应用[J]. 中国药物化学杂志, 2009, 19(6) |
| |
| 作者姓名： | 刘 宝 尹 璐 贾 娴 黎星术 |
| |
| 作者单位： | ;（1. 中山大学 药学院，广东 广州 510006； ;2. 沈阳药科大学 制药工程学院，辽宁 沈阳 110016) ; |
| |
| 摘 要： | 目的 使用不对称亨利反应合成沙美特罗。方法 以4-苯基丁醇为起始原料合成长链脂肪醛，同时由对羟基苯甲醛出发经3步反应制备前手性苯甲醛,继而通过不对称亨利反应制得手性硝基醇化合物，随后用氢化方法合成(R)-沙美特罗。结果与结论 通过不对称亨利反应制得硝基醇化合物，产物的对映选择性较好(60% ee)，新路线省去了原文献中制备三级胺和脱苄基两步反应，合成路线未见报道。
|
| 关 键 词： | 不对称亨利反应；(R)-沙美特罗；合成 |
| 收稿时间： | 2009-08-20 |
| 修稿时间： | 2009-10-10 |
Application of asymmetric Henry reaction in the synthesis of (R)-salmeterol |
| |
| LIU Bao,YIN Lu,JIA Xian,LI Xing-shu. Application of asymmetric Henry reaction in the synthesis of (R)-salmeterol[J]. Chinese Journal of Medicinal Chemistry, 2009, 19(6) |
| |
| Authors: | LIU Bao YIN Lu JIA Xian LI Xing-shu |
| |
| Affiliation: | （1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; 2. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China) |
| |
| Abstract: | Aim To synthesize (R)-salmeterol by asymmetric Henry reaction . Methods Long chain aliphatic aldehyde was prepared from 4-phenyl-1-butanol and prochiral benzaldehyde was achieved through three steps with p-hydroxy-benzaldehyde as starting material. Asymmetric Henry reaction afforded the chiral nitroalcohol intermediate which was conveniently transformed into the corresponding aminoalcohol compound for further use in the synthesis of (R)-salmeterol. Results and conclusion The nitroalcohol intermediate was obtained by asymmetric Henry reaction for the first time with moderate enantioselectivity (60% ee); The synthetic route was simplified by avoiding preparation of tertiary amine and debenzylation in traditional methods. |
| |
| Keywords: | asymmetric Henry reaction (R)-salmeterol preparation |
|
| 点击此处可从《中国药物化学杂志》浏览原始摘要信息 |
|
点击此处可从《中国药物化学杂志》下载全文 |
