不对称亨利反应在(R)-沙美特罗合成中的应用

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。

Application of asymmetric Henry reaction in the synthesis of (R)-salmeterol

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.