手性丹参素异丙酯的不对称合成方法优化研究

Modification of asymmetric synthesis method for Danshensu isopropanol ester

目的优化改进手性丹参素异丙酯的不对称合成方法。方法以3,4-二羟基苯甲醛经过苄基保护、Knoevenagel缩合和酯化反应生成(E)-3-(3,4-二苄氧基苯基)丙烯酸异丙酯,并通过Sharpless不对称双羟化反应构建手性中心,以三乙氧基硅烷(Et_3SiH)及三氟乙酸(CF_3COOH)为选择性脱氧试剂,最后常温常压条件下催化加氢脱保护得到目标产物。结果该方法中原料、Et_3SiH与CF_3COOH最佳比例为1∶3∶10,手性丹参素异丙酯对映选择性(ee)大于99. 9%且化学产率良好,其化学结构式均由核磁(~1H-NMR)及高分辨质谱(HRMS)证实。结论实验证实了手性丹参素异丙酯优化改进的不对称合成方法简单可行,光学纯度高,具有一定的实际应用价值。

Objective To optimize the asymmetric synthesis method of Danshensu isopropanol ester.Methods The 3,4-dihydroxybenzaldehyde,which was reacted with benzyl chloride and propandioic acid successively,was used to obtain(E)-3-(3,4-dibenzyloxypheny)acrylic acid isopropanol ester.Then the asymmetric synthesis of chiral molecule 3-(3,4-dibenzyloxyphenyl)-2,3-dihydroxy propionic acid isopropanol ester was achieved by Sharpless dihydroxylation.Finally,the desired product was obtained in Et 3SiH and CF 3COOH solution by the selective hydrogenation.Results For 3-(3,4-dibenzyloxyphenyl)-2,3-dihydroxy propionic acid isopropanol ester,Et 3SiH and CF 3COOH,the best mole ratio was 1∶3∶10.The enantionmeric excesses of Danshensu isopropanol ester was ee>99.9%by the chiral HPLC columns.The structure of products was characterized by 1H-NMR and high-resolution MS techniques.Conclusion The results suggest that the asymmetric synthesis of Danshensu isopropanol ester is a new simple method and could be used in the practical application.