9-芴甲氧羰基氨基保护试剂的合成与分析

Study of 9-Fluorenylmethoxycarbonyl Amino Protective Agents

研究了9 芴甲基氯甲酸酯(Fmoc Cl)、9 芴甲基叠氮甲酸酯(Fmoc N3)和9 芴甲基琥珀酰亚胺碳酸酯(Fmoc OSu)这3种氨基保护试剂的合成方法。用碳酸二(三氯甲酯)代替光气与芴甲醇反应得到Fmoc Cl;Fmoc Cl可分别与叠氮化钠及N 羟基琥珀酰亚胺反应得到9 芴甲基叠氮甲酸酯(Fmoc N3)以及9 芴甲基琥珀酰亚胺碳酸酯(Fmoc OSu),收率分别为87 9%和86 9%。上述Fmoc保护试剂在碱性条件下分别与甘氨酸反应进行氨基保护得到产品Fmoc 甘氨酸,收率分别为83 1%、73 3%及93 9%,用毛细管电泳仪分析其摩尔分数分别为97 7%、99 5%及大于99 9%,结果表明,Fmoc OSu是甘氨酸Fmoc氨基保护的最佳试剂。

Synthetic methods for three kinds of Fmoc (9-fluorenylmethoxycarbonyl) amino protective agents were studied:9-fluorenylmethoxycarbonyl chloroformate (Fmoc-Cl),9-fluorenylmethoxycarbonyl azidoformate (Fmoc-N_3) and succinimidyl-9-fluorenylmethoxycarbonyl carbonate (Fmoc-OSu).Fmoc-Cl was obtained from 9-fluorenylmethanol and bis(trichloromethyl) carbonate instead of phosgene.Fmoc-N_3 and Fmoc-OSu were synthesized from Fmoc-Cl separately with triazosodium and N-hydroxysuccinimide in 87.9% and 86.9% yields respectively.Furthermore,Fmoc-glycine was obtained from glycine separately with different Fmoc protective agents in basic condition in the yields of 83.1%,73.3% and 93.9%.The products obtained were analyzed by capillary electrophoresis to give the purity of 97.7%,99.5% and >99.9%.The results indicated that Fmoc-Osu is the best amino protective agent of glycine.