连续流微通道技术合成黄酮类天然产物

Syntheses of the Flavonoid Compounds by Continuous Flow Microchannel Technology

本文采用连续流微通道反应技术,通过碘介导的二氢黄酮的氧化反应对黄酮类化合物半合成工艺进行了研究。首先选择黄酮类代表药物地奥司明为研究对象,通过连续流微通道反应器分别考察了在常压和背压条件下不同反应条件的影响,实现橙皮苷转化率98%,产品地奥司明收率90%。然后,采用连续流微通道反应完成了多种黄酮、黄酮醇和异黄酮类天然产物的合成。本文研究的黄酮类天然产物的连续流微通道反应工艺,不仅实现了与传统工艺相当的转化率和收率,而且反应时间从传统工艺的8~20h缩短到2~3min,反应过程更加安全、高效和快捷,同时拓展了连续流微通道反应技术在药物合成领域的应用范围。

The continuous flow microchannel reaction technology was used to research the semi-synthesis of the flavonoid compounds via iodine-mediated oxidation. Firstly, the synthetic methods of a flavonoid compound Diosmin were investigated through the continuous flow microchannel reactor with normal pressure and back pressure, respectively. The optimized continuous flow microchannel reaction conditions were thus obtained. The conversion rate of the starting material hesperidin reached 98%, and the yield of the product Diosmin reached 90%. Then, other flavonoid compounds included flavonoids, flavonols and isoflavones were successfully synthesized. The continuous flow microchannel reaction process of natural flavonoids studied in this paper not only achieves the conversion rate and yield equivalent to the traditional process, but also shortens the reaction time from 8~20 h of the traditional process to 2~3 min, and the reaction process is more safe, efficient and fast. The application of continuous flow microchannel reactive technology in pharmaceutical synthesis is further expanded.