拉米夫定的合成

Synthesis of lamivudine

摘要:

摘 要:研究了新一代嘧啶核苷类抗病毒药物拉米夫定的合成方法，以L-薄荷醇和乙醛酸为原料，合成L-薄荷醇乙醛酸酯为手性源，经酯化、环合、氯代、缩合、还原5 步反应制得目标产物。在 MGH 合成过程中, L-薄荷醇和乙醛酸的最佳摩尔比为3:1；用双(三氯甲基)碳酸酯代替二甲基亚砜做氯代试剂制备NA，收率为60.3%；利用硼氢化钠-甲醇-四氢呋喃体系还原NA，反应4h得到拉米夫定，收率84.8%。产品总收率30.9%，并通过IR、MS等方法对化合物进行了结构表征。

Abstract:

Abstract：The synthetic method of typical antivius agent of pyrimidine nucleoside lamivudine is reported.(1R)-(-)-Menthyl glyoxylate hydrate was synthesized from L-menthol and glyoxylic acid by a five-step way including esterification,cyclization,chlorination,condensation and reduction. In the synthesis process of MGH, the perfect molar ratio was n(L-menthol):n(glyoxylic acid)=3:1; In the synthesis process of NA, triphosgene replaced dimethyl sulfoxide and the yield was 60.3%. NA was reduced to lamivudine using sodium borohydride- methanol -THF system，which gave the 84.8% yield.The total yield reached 30.9% and the objective product was characterized with MS and IR