Glycyrrhizic acid (GA, 1) is the main triterpene glycoside from roots of Glycyrrhiza glabra L. and G. uralensis Fisch. and a leading natural glycoside with potential as a medicine for developing new immunomodulators and antiviral agents [1, 2]. Several conjugates of GA with amino acids and dipeptides displayed pronounced antiviral activity against human immunodeficiency (HIV) [3, 4], atypical pneumonia of SARS-CoV [5], Epstein–Barr [6], and flu A/H1N1 viruses [7]. Previously, we proposed methods for preparing conjugates of GA with alkyl and benzyl esters of Land D-amino acids via activation of the GA carboxylic acids using N-hydroxybenzotriazole (HOBt) and N,N′-dicyclohexylcarbodiimide (DCC) [8], N-hydroxyphthalimide and DCC [9], or N-hydroxysuccinimide (HOSu) and DCC [3]. The main drawback of these methods for preparing amino-acid conjugates of GA is their two steps (preparation of GA activated ester and subsequent reaction of it with an amine). Furthermore, the dicyclohexylurea formed if DCC is used contaminates the target conjugates. Therefore, water-soluble carbodiimides, in particular 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (DEC), which does not form dicyclohexylurea, are more attractive as condensing reagents. The present communication reports the selective synthesis of amino-acid conjugates of GA with free amino acids in the glycoside carbohydrate part using DEC and L-amino-acid t-butyl ester hydrochlorides.

中文翻译：

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1-(3-二甲氨基丙基)-3-乙基碳二亚胺在甘草酸氨基酸缀合物合成中的应用


甘草酸 (GA, 1) 是来自光果甘草和乌拉尔甘草根部的主要三萜糖苷。以及一种领先的天然糖苷，有潜力作为开发新型免疫调节剂和抗病毒药物的药物 [1, 2]。 GA 与氨基酸和二肽的几种缀合物对人类免疫缺陷 (HIV) [3, 4]、SARS-CoV 非典型肺炎 [5]、Epstein-Barr [6] 和流感 A/H1N1 病毒 [7] 显示出显着的抗病毒活性。 ]。此前，我们提出了通过使用 N-羟基苯并三唑 (HOBt) 和 N,N'-二环己基碳二亚胺 (DCC) 活化 GA 羧酸来制备 GA 与 Land D-氨基酸的烷基酯和苄酯缀合物的方法 [8]，N -羟基邻苯二甲酰亚胺和 DCC [9]，或 N-羟基琥珀酰亚胺 (HOSu) 和 DCC [3]。这些制备 GA 氨基酸缀合物的方法的主要缺点是它们的两个步骤（GA 活化酯的制备以及随后其与胺的反应）。此外，如果使用 DCC，则形成的二环己基脲会污染目标缀合物。因此，不形成二环己基脲的水溶性碳二亚胺，特别是1-乙基-3-(3-二甲氨基丙基)碳二亚胺盐酸盐(DEC)作为缩合试剂更有吸引力。本通讯报道了使用DEC和L-氨基酸叔丁酯盐酸盐选择性合成GA与糖苷碳水化合物部分中的游离氨基酸的氨基酸缀合物。