| 第 39 卷第 5 期 |  | Vol. 39 No. 5 | | 2009 年 10 月 | Oct 2009 |
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所屬欄目：醫藥及中間體
Nα-9-芴甲氧羰基-Nε-叔丁氧基羰基-L-賴(lài)氨酸的合成研究 |
| 劉美艷1，曾佑林1，楊鵬彪1，李葉華2，羅冬文2，蘇勝培1*
（1． 湖南師范大學(xué) 化學(xué)與化工學(xué)院，湖南 長(cháng)沙，410081；2． 長(cháng)沙同瑞醫藥科技開(kāi)發(fā)有限公司，湖南 長(cháng)沙，410013） |
| 摘 要：以水-丙酮為反應溶劑，用五水硫酸銅對L-賴(lài)氨酸α-氨基和羧基進(jìn)行絡(luò )合保護，再在縛酸劑和催化劑碳酸氫鈉作用下與二碳酸二叔丁酯（Boc酸酐）反應制得Nε-Boc保護的賴(lài)氨酸銅絡(luò )合物。然后用脫銅試劑解釋賴(lài)氨酸銅絡(luò )合物α-氨基，以碳酸鈉為催化劑、水-丙酮為反應溶劑，制備了Nα-9-芴甲氧羰基-Nε-叔丁氧基羰基-L-賴(lài)氨酸（Fmoc-L-Lys（Boc）-OH）�？疾炝�4種脫銅試劑對Fmoc-L-Lys（Boc）-OH制備的影響，結果表明硫化鈉和8-羥基喹啉是良好的脫銅試劑。以8-羥基喹啉為脫銅試劑，對Fmoc-L-Lys（Boc）-OH生產(chǎn)的工藝條件進(jìn)行考察。優(yōu)化工藝條件為：n（賴(lài)氨酸銅絡(luò )合物） ∶ n（Fmoc-Osu）=1.00 ∶ 0.98，室溫反應3 h，Fmoc-L-Lys（Boc）-OH的收率達91.7%，純度99.1%。 |
| 關(guān)鍵詞：L-賴(lài)氨酸；L-賴(lài)氨酸銅絡(luò )合物；脫銅試劑；Fmoc-L-Lys（Boc）-OH |
| 中圖分類(lèi)號：R977.4 文獻標識碼：A 文章編號：1009-9212（2009）05- 0026-04 |
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| 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 |
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基金項目：湖南省教育廳資助科研資助項目（06C513）。
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作者簡(jiǎn)介：劉美艷（1973-），女，湖南溆浦人，碩士研究生，研究方向：有機化工和醫藥中間體的合成。（E-mail：xplmy@yahoo.com.cn）
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聯(lián) 系 人：蘇勝培（1966-），男，教授，博士生導師，研究方向：有機合成和高分子材料。（E-mail：sushengpei@gmail.com)
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收稿日期： 2009-10-0
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