根据HCMV蛋白酶晶体结构和拟肽类抑制剂与酶复合物的晶体结构数据 ,设计了拟肽类HCMV蛋白酶抑制剂化合物库Ⅰ ,并拟采取液相组合方式 ,通过两步策略 ,首先由四种构建块分子 :羧酸、胺、醛或酮和异腈 ,经Ugi四组分缩合反应生成Ⅱ ,然后氧化来合成化学库。介绍其中最重要的构建块异腈Ⅲ的前体Ⅳ的合成。首先将酒石酸二乙酯由相应胺进行酰胺化产生酒石酸二酰胺Ⅴ。酒石酸二酰胺用过碘酸氧化裂解产生乙醛酸酰胺Ⅵ ,然后不经分离 ,直接在KF 氧化铝的催化下完成硝基乙烷的加成。由此生成的 2 羟基 3 硝基丁酰胺Ⅶ可经Zn +NH4 Cl或Zn +NH4 Cl+催化量 10 %Pd C还原为 2 羟基 3 氨基丁酰胺Ⅷ ,再经过氨基的甲酰化生成 2 羟基 3 甲酰胺基丁酰胺Ⅳ。但是在甲酸乙酯存在下 ,用H2 /Pd C对Ⅶ的硝基进行还原 ,得到的Ⅷ中的氨基可当即被甲酰化 ,使由Ⅶ到Ⅳ的两步反应一步完成 According to the crystal structure of HCMV protease and the crystal structure of the peptidomimetic inhibitor and enzyme complex, a library of HCMV protease inhibitor compound Ⅰ was designed and the liquid phase combination was proposed. Through the two-step strategy, Building block molecules: carboxylic acids, amines, aldehydes or ketones and isonitriles, Ugi four component condensation reaction II, and then oxidized to synthesize chemical libraries. The synthesis of precursor IV, the most important building block among isonitrile III, is introduced. The tartaric acid diethyl ester is first amidated from the corresponding amine to produce tartaric acid diamide V. Tartaric acid diamide is oxidatively cleaved with periodic acid to produce glyoxylic acid amide VI, and then the nitroethane is directly added to KF alumina without isolation. The 2-hydroxy-3-nitrobutylamide VII thus obtained can be reduced to 2-hydroxy-3-aminobutylamide VIII by Zn + NH 4 Cl or Zn + NH 4 Cl + in a catalytic amount of 10% Pd C to form 2-hydroxy 3 Formamide Butyramide IV. However, reduction of the nitro group of VII by H2 / Pd C in the presence of ethyl formate gives the amino group of VIII as it is immediately formylated to complete the two-step reaction from VII to IV in one step