N^α-9-芴甲氧羰基-N^ε-叔丁氧基羰基-L-赖氨酸的合成研究  

Study on the Synthesis of Fmoc-L-Lys(Boc)-OH

作　　者：刘美艳[1] 曾佑林[1] 杨鹏彪[1] 李叶华 罗冬文 苏胜培[1] 

机构地区：[1]湖南师范大学化学与化工学院,湖南长沙410081 [2]长沙同瑞医药科技开发有限公司,湖南长沙410013

出　　处：《精细化工中间体》2009年第5期26-29,共4页Fine Chemical Intermediates

基　　金：湖南省教育厅资助科研资助项目(06C513)

摘　　要：以水-丙酮为反应溶剂,用五水硫酸铜对L-赖氨酸α-氨基和羧基进行络合保护,再在缚酸剂和催化剂碳酸氢钠作用下与二碳酸二叔丁酯(Boc酸酐)反应制得Nε-Boc保护的赖氨酸铜络合物。然后用脱铜试剂解释赖氨酸铜络合物α-氨基,以碳酸钠为催化剂、水-丙酮为反应溶剂,制备了Nα-9-芴甲氧羰基-Nε-叔丁氧基羰基-L-赖氨酸(Fmoc-L-Lys(Boc)-OH)。考察了4种脱铜试剂对Fmoc-L-Lys(Boc)-OH制备的影响,结果表明硫化钠和8-羟基喹啉是良好的脱铜试剂。以8-羟基喹啉为脱铜试剂,对Fmoc-L-Lys(Boc)-OH生产的工艺条件进行考察。优化工艺条件为:n(赖氨酸铜络合物)∶n(Fmoc-Osu)=1.00∶0.98,室温反应3h,Fmoc-L-Lys(Boc)-OH的收率达91.7%,纯度99.1%。Using H2O-acetone as solvent, sodium bicarbonate as acid binder and catalyst, N^ε-tert-butoxycarbony- L-lysine copper （Ⅱ） complex was synthesized successfully by Nε-tert-butoxycarbonylation of L-lysine copper （Ⅱ） complex which was furnished by protection of the α-amino and carbonyl of L-lysine with copper （Ⅱ） sulfate pentahydrate. The free α-amino was released from Nε-tert -butoxycarbonylation of L-lysine copper （Ⅱ）complex promoted by copper catching regent, and followed by Nα-9-fluorenylmethyloxycarbonylation catalysted by sodium carbonate with H2O-acetone as solvent to form Nα-9-fluorenylmethyloxycarbonyl-Nε-tert-butyloxycarbonyl-l-lysine （Fmoc-L-Lys （Boc） -OH）. The effects of four kinds of copper catching regents on the Nα -9- fluorenylmethyloxycarbonylation were studied, and the results showed the excellent copper catching regent were sodium sulfide and 8-hydroxyquinoline. The reaction conditions of Nα-9-fluorenylmethyloxycarbonylation such as ratio of Nε-tert-butoxycarbony-L-lysine copper （Ⅱ） complex to Fmoc-Osu, reaction time, reaction temperature were investigated in detail. The optimum reaction conditions were obtained as follow： the mole ratio of Nε-tert- butoxycarbony-L-lysine copper （Ⅱ） complex to Fmoc-Osu is 1.00 ： 0.98, the reaction temperatureare is room temperatureare and the reaction time is 3 h. Under those conditions, Fmoc-L-Lys （Boc）-OH was reached in 91.7% yield with 99.1% purity.

关 键 词：L-赖氨酸 L-赖氨酸铜络合物 脱铜试剂 Fmoc—L—Lys(Boc)-OH 

分 类 号：R977.4[医药卫生—药品]