12-对甲基苯酰氧基-14-脱氧穿心莲内酯合成工艺改进

Process Improvement on the Synthesis of 12-Methyl Benzoyloxy-14-deoxy Andrographolide

为了较高收率地获得12-对甲基苯酰氧基-14-脱氧穿心莲内酯，对其合成工艺中的酯化反应进行优化研究。发现反应时间、原料投料比、溶剂用量、缩合剂用量分别为22h，1：1．1，1：25，1：1．2时为佳，且使用缩合剂DIC时的反应收率最高，使用缩合剂EDAC时副产物最少。此外，对起始原料穿心莲内酯进行重结晶纯化有利于减少副产物。经上述反应优化后，总收率可达15．3％。中间体及目标产物的结构均经1H-NMR、13C-NMR、IR和MS确证。

To synthesize 12-methyl benzoyloxy-14-deoxy andrographolide in good yield, the esterification in the synthetic process was optimized. It was found that the optimum reaction time, reactant ratio, reactant/solvent ratio, and the reactant/condensation agent ratio was 22 h, 1 ： 1. 1, 1 ： 25, 1 ： 1.2, respectively, with the highest yield when the condensation agent was DIC, and the fewest by-product when the condensation agent was EDAC. In addition, the recrystallization of andrographolide was benefit to reduce by-product. The total yield could be over 15.3% after the above optimization. The structure of intermediates and target product were identified by IR, NMR and MS.