甘氨酸二肽合成中缩合剂的选择

Selection of Condensing Agents for Synthesis of Glycine Dipeptide

甘氨酸二肽是一分子甘氨酸的α-羧基和另一分子甘氨酸的α-氨基脱水缩合形成的酰胺键(即-CO-NH-)组成的蛋白质片段或物质。其结构比蛋白质简单,相对分子质量小,在人体内具有生物活性,可以调节人体的各项机能,因此被更多地应用于食品、药物、组织工程材料等不同的领域。以甘氨酸为研究对象,用二碳酸二叔丁酯(Boc_2O)保护甘氨酸的α-氨基,分别采用N,N′-二环已基碳二亚胺(DCC),2-(7-偶氮苯并三氮唑)-N,N,N′,N′-四甲基脲六氟磷酸酯(HATU)、苯并三氮唑-1-基氧基三(二甲基氨基)磷鎓六氟磷酸盐(BOP)三种缩合剂活化甘氨酸的羧基形成活泼酯,再与甘氨酸缩合形成含有两个甘氨酸的小分子肽。通过对三种缩合方法的对比和结果分析,活化试剂对小分子肽的合成影响显著;甘氨酸二肽(Boc-G1y-Gly-OH)合成的最佳反应条件为:以BOP为缩合剂,乙腈水溶液为反应体系,生成活泼酯的反应温度为45℃,小分子肽的产率为78.2%。合成的Boc-G1y-G1y-OH二肽经红外光谱、质谱等袁征,结构得到验证,为氨基酸活泼酯的合成及小分子多肽液相合成提供了实验依据和理论参考。

Glycine dipeptide was synthesized by binding the a-carboxyl group of one glycine molecule with the a-amino group of another. Because of its smaller molecular weight and simpler structure as compared with proteins and its complex and specific physiological activity for many organs in the body, it is in com- mon use in many areas, like foods, drugs and tissue engineering materials. Glycine was choosed as the main object of this study. Di-tert-butyl dicarbonate was used to protect the a-amino group of glycine and the carboxyl group of glycine was activated by three different condensing agents such as DCC, HATU and BOP to form active ester. Glycine was condensed to prepare small molecule peptide that contained two gly- cine molecules. The experimental results showed that the coupling reagent played a key role in the synthe- s^s of small molecule peptide. The optimal conditions of synthesing Boc-Gly-Gly-OH was as follows： BOP was selected as the condensating agent; acetonitrile was used as the solvent; and the reaction temperature was 45℃. The yield was 78.20%. The structure of Boc-Gly-Gly-OH was confirmed by IR and MS spectra. This work provides the experimental basis and theoretical reference for synthesis of amino acid active ester and small molecule peptide.