恩曲他滨的合成新工艺研究  

Novel Process Research on Emtricitabine Synthesis

作　　者：顾继山 李苏 谢志翰 吴晓宇[1] 熊芸[1] 刘生鹏[1] GU Ji-shan;LI Su;XIE Zhi-han;WU Xiao-yu;XIONG Yun;LIU Sheng-peng(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China)

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430205

出　　处：《化学试剂》2020年第8期1004-1008,共5页Chemical Reagents

基　　金：湖北省技术创新专项重大项目(2017ACA086)。

摘　　要：研究新型核苷类逆转录酶抑制剂标题化合物合成新方法。以L-氯甲酸薄荷酯与乙二醇为起始原料,经酯化、氧化、环化、卤化、偶合、水解6步反应合成标题化合物,总产率为27.62%。并着重对乙二醇L-薄荷碳酸酯的合成进行了研究,确定了其最佳合成工艺条件为:无溶剂法以吡啶为缚酸剂,反应温度为-5℃,反应时间为2 h。通过此工艺合成乙二醇L-薄荷碳酸酯的产率可达81%。合成的化合物均经1^HNMR、13^CNMR确证。合成工艺避开了传统工艺对甲醛、浓硫酸、硼氢化钠、氢化铝锂等危险试剂的使用,具有成本低、反应条件温和、绿色环保、高规模化生产能力及可操作性等优点。A novel process on a novel nucleoside analogue reverse transcriptase inhibitor Emtricitabine synthesis was established.Emtricitabine was synthesized from L-menthylchloroformate and ethylene glycol by a six-step way including esterification,oxidation,cyclization,halogenation,coupling and hydrolysis.The overall yield was 27.62%.The synthesis of glycol L-menthol carbonate was investigated in detail,leading to an optimal process conditions:solvent-free,pyridine as acid binding agent,reaction temperature-5℃and reaction time 2 h.The yield of glycol L-menthol carbonate synthesized by the process was 81%.The chemical structures of compounds were confirmed via 1^HNMR and 13^CNMR.The method obviated the use of dangerous reagents such as formaldehyde,concentrated sulfuric acid,sodium borohydride,lithium aluminum hydride by traditional processes,and has the advantages of lower cost,mild reaction condition,environmentally friendly,higher scale production capacity and maneuverability.

关 键 词：恩曲他滨 L-氯甲酸薄荷酯 抗HIV药 合成 

分 类 号：O626.2[理学—有机化学]