多肽中间体氨基酸活泼酯的合成

多肽合成中,氨基酸的保护及氨基酸活化反应对多肽合成的产率及纯度具有重要影响,所以对氨基酸保护及活化反应进行研究,是多肤合成的一个重要环节。采用四氢呋喃作为反应溶剂,以9-芴甲氧羰基为保护基团保护组氨酸氨基,以2-(7-偶氮苯并三氮唑)-N、N,N′,N′-四甲基脲六氟磷酸酯(HATU)为缩合试剂,活化组氨酸形成活泼酯。建立了芴甲氧羰基-组氨酸活泼酯的合成方法,优化了氨基酸活泼酯的制备条件。结果表明:溶剂和活化试剂对活泼酯的产率影响显著;活泼酯制备的最佳反应条件为n(Fmoc-His):n(HATU)=1:1.1,溶剂为THF,反应温度为25℃,产率为68.20%。此方法节省原料,并大大简化了实验操作。

Preparation of Amino Acid Active Ester in Peptide Intermediate

The yield and purity of synthetic peptides were greatly affected by the amino acid protection and activation reaction in peptides synthesis.Study on the amino acid protection and activation reaction is one of the important links in peptide synthesis.Using tetrahydrofuran as the solvent,9- fluorenylmethoxycarbonyl as protection group to protect histidine amino,and 2-(7-azobenzotriazol-l-yl)-N, N,N′,N′-tetramethyluronium hexafluorophosphate(HATU)as condensation reagent to activate histidine form active ester,a synthesis method for N-(9- fluorenylmethoxycarbonyl)-histidine active ester was established.The reaction conditions for preparing this active ester were optimized.The experimental results indicated that solvents and active reagents had a remarkable effect on the yield of active ester.The best conditions for preparing the active ester were n(Fmoc-His):n(HATU)=1:1.1,THF used as the solvent and at a temperature of 25℃.The productivity was 68.20%.This method not only saved raw materials,but also greatly simplified the experimental operation.