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。在乙醛酸-L-薄荷酯(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作氯代试剂制备(2R,5S)-5-(胞嘧啶-1′-基)-[1,3]-氧硫杂环戊烷-2-羧酸-L-薄荷酯(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。
The synthetic method of the typical antivius agent of pyrimidine nucleoside lamivudine is reported.（1R）-（L）-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.
出处
《精细化工》
EI
CAS
CSCD
北大核心
2010年第6期589-592,共4页
Fine Chemicals
