第 39 卷第 5 期 Vol. 39 No. 5 2009 年 10 月 Oct 2009

所属栏目：医药及中间体 Nα-9-芴甲氧羰基-Nε-叔丁氧基羰基-L-赖氨酸的合成研究

刘美艳1，曾佑林1，杨鹏彪1，李叶华2，罗冬文2，苏胜培1* （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）

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3 h，Fmoc-L-Lys（Boc）-OH的收率达91.7%，纯度99.1%。

关键词：L-赖氨酸；L-赖氨酸铜络合物；脱铜试剂；Fmoc-L-Lys（Boc）-OH

中图分类号：R977.4　　文献标识码：A　　文章编号：1009-9212（2009）05- 0026-04

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

（1. College of Chemistry and Chemical Engineering，Hunan Normal University，Changsha 410081，China；2. Changsha Tongrui Pharmaceuticals Science Technic Development Co.，Ltd.，Changsha 410013，China）

Abstract：Using H2O-acetone as solvent，sodium bicarbonate as acid binder and catalyst，Nε-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.

Key words：L-lysine；L-lysine copper（II） complex；copper catching regent；Fmoc-L-Lys（Boc）-OH

基金项目：湖南省教育厅资助科研资助项目（06C513）。

作者简介：刘美艳（1973-），女，湖南溆浦人，硕士研究生，研究方向：有机化工和医药中间体的合成。（E-mail：xplmy@yahoo.com.cn）

联 系 人：苏胜培（1966-），男，教授，博士生导师，研究方向：有机合成和高分子材料。（E-mail：sushengpei@gmail.com)

收稿日期： 2009-10-0