一种强力霉素关键中间体的合成研究

Synthesis of the key intermediate of doxycycline

11α-氯代甲烯土霉素是合成强力霉素的关键中间体。本文以N-氯代乙酰苯胺和土霉素为起始原料,经氯代、脱水、成盐三步反应得到目标化合物,其结构经核磁共振氢谱、红外光谱确认,总收率达82.2%。本合成方法中所用新脱水剂的环境污染小、对设备腐蚀小、产品收率高,更适于工业化推广。

The key intermediate of doxycycline,11α-chloro-metacycline,was synthesized from N-chloro acetanilide and oxytetracycline in three steps including chlorination,dehydration and salification.The structure of the intermediate was characterized by 1H NMR and HRMS.The overall yield of the synthetic route was 82.2%.The new dehydrant used in this method had the advantages of less pollution,lower corrosion and higher yield compared with anhydrous hydrogen fluoride,and it was more suitable for industrial application.