N~δ-保护鸟氨酸的微波合成研究

Synthesis of N~δ-protective Ornithine under Microwave Irradiation

[目的]用微波法合成Nδ-保护鸟氨酸。[方法]以L-鸟氨酸盐酸盐为原料,与碱式碳酸铜反应得到L-鸟氨酸铜络合物,在δ-氨基上分别引入苄氧羰基、叔丁氧羰基、芴甲氧羰基、乙酰基和邻苯二甲酰基,得到了Nδ-保护鸟氨酸铜络合物,微波辐射下用EDTA-2Na脱去铜离子,得到了Nδ-苄氧羰基鸟氨酸、Nδ-叔丁氧羰基鸟氨酸、Nδ-芴甲氧羰基鸟氨酸、Nδ-乙酰基鸟氨酸和Nδ-邻苯二甲酰基鸟氨酸5个Nδ-保护鸟氨酸。探讨了微波辐射功率、时间及投料比对脱铜反应的影响。[结果]脱铜反应的最佳反应条件为:n(Nδ-保护鸟氨酸铜络合物)∶n(EDTA)=1∶1.1～1∶1.2,微波辐射功率为250～300 W,反应时间为4～6 min,收率分别为93.2%、86.2%、88.7%、86.3%和86.4%(以Nδ-保护鸟氨酸铜络合物计)。产物结构经元素分析和1H NMR确证。[结论]该合成工艺对环境友好、简便、高效,产物收率与纯度均较高。

[Objective]To synthesis Nδ-protective ornithine under microwave irradiation.[Method]L-ornithine monohydrochloride was first reacted with basic curpic carbonate to give L-ornithine copper complexes.Subsequently,the δ-amino was protected with tert-butoxycarbonyl（Boc）,benzyloxycarbonyl（Z）,fluorenylmethyloxycarbonyl（Fmoc）,acetyl（Acetyl） and phthaloyl（Phthalyl）,after the use of EDTA-2Na for copper removal,the Nδ-benzyloxycarbonyl ornithine（H-Orn（Z）-OH）,Nδ-tert-butoxycarbonyl ornithine（H-Orn（Boc）-OH）,Nδ-fluorenylmethyloxycarbonyl ornithine（H-Orn（Fmoc）-OH）,Nδ-acetyl ornithine（H-Orn（Acetyl）-OH） and Nδ-phthaloyl ornithine（H-Orn（Phthalyl）-OH） were obtained.Finally,the microwave irradiation technology was applied for the removal of copper to explore the effects of microwave radiation power,time and the proportion of materials on yield.[Result]The optimal conditions were obtained as follows： n（Nδ-protective ornithine copper complexes）∶ n（EDTA）=1∶ 1.1-1∶ 1.2,microwave power was 250-300 W,reaction time was 4-6 min.The yield of Nδ-benzyloxycarbonyl-L-Ornithine,Nδ-tert-butyloxycarbonyl-L-Ornithine,Nδ-fluorenylmethyl-oxycarbonyl-L-Ornithine,Nδ-acetyl-L-Ornithine and Nδ-phthalyl-L-Ornithine were 93.2%,86.2%,88.7%,86.3% and 86.4% respectively.The structure of aimed compounds was confirmed by elementary analysis and 1H NMR.[Conclusion] The improved synthetic route was environment friendly and convenient in operation with better product yield and purity.