泊沙康唑合成工艺研究及结构确证

Study on synthesis technology and structure confirmation of posaconazole

泊沙康唑是第二代三唑类抗真菌药物,其抗菌谱广、生物利用度高、耐药性低。为了寻求其适合工业化制备的工艺,本研究对泊沙康唑原料药的合成方法进行了优化改进,开发了一种高效,绿色,安全的泊沙康唑原料药工业化生产工艺。以1-(4-氨基苯基)-4-(4-羟基苯基)哌嗪为起始原料,经“一锅多步”、取代、脱苄基等三步反应得到泊沙康唑粗品,经重结晶得泊沙康唑,三步反应总收率66%。所得产品符合药典要求。通过对所得泊沙康唑进行红外吸收光谱(IR)、高分辨质谱(HRMS)、核磁共振(NMR)波谱等技术进行结构解析,确证了泊沙康唑的结构。

Posaconazole,as a second-generation antifungal drug bearing a triazole skeleton,shows broad antibacterial spectrum,high bioavailability and low drug resistance properties.Through optimizing the synthetic methods of posaconazole,this study developed a highly,green and safe way to better meet its industrial production.Specifically,from the starting raw material 1-(4-aminophenyl)-4-(4-hydroxyphenyl)piperazine,posaconazole crude product was offered via three step reactions,including“one pot multi-step”reac-tion,substitution reaction and debenzylation reaction.Next,posaconazole was further purified to better meet pharmacopoeia standards through recrystallization with the yield of 66%.Finally,posaconazole was confirmed through using several technologies,including IR,HRMS and NMR.