氘代氨基酸的合成工艺研究

发布时间：2018-05-23 15:40

  本文选题：氘 + 氨基酸　； 参考：《佳木斯大学》2014年硕士论文

【摘要】：目的寻找氘代氨基酸简便快捷有效的合成方法，从而降低成本并根据所寻找的方法合成α-氘代氨基酸，为建立新生儿氨基酸代谢异常检测平台做好前期工作。 方法选择重水交换法作为氘代氨基酸的合成方法。（1）探索反应温度、反应时间和交换次数对合成氘代L-组氨酸的影响；（2）以L-[α,2,4-2H3]-组氨酸的单因素实验条件为参考进行L-[α,2,4-2H3]-组氨酸的响应面优化实验；（3）以L-[α,2,4-2H3]-组氨酸响应面因素为参考，根据氨基酸的酸、碱、中性选择L-[α-2H]-谷氨酸和L-[α-2H]-甲硫氨酸进行响应面优化实验。（4）根据响应面所优化出的条件，依次合成L-[α-2H]-脯氨酸、L-[α-2H]甘氨酸、L-[α-2H]异亮氨酸以及L-[α-2H]缬氨酸。所得到氘代氨基酸经1H-NMR测试并计算其氘代率，圆二色谱鉴定氘代后的构型是否发生变化以及通过质谱手段进行定性分析。 结果（1）响应面法优化L-[α,2,4-2H3]-组氨酸的最优合成条件是：反应时间为6.47h，反应温度为185℃，交换次数为3次。（2）响应面法优化L-[α-2H]-甲硫氨酸的最优合成条件是：反应时间6.23h，反应温度为182℃，，交换次数为3次。（3）响应面法优化L-[α-2H]-谷氨酸的最优合成条件是：反应时间7.15h，反应温度为189℃，交换次数为3次。（4）合成的氘代氨基酸经1H-NMR鉴定氘代率均在98.5%以上，圆二色谱检测结果表明构型均未改变，质谱检测结果证明1H-NMR所得氘代数目正确。 结论重水交换法是合成氘代氨基酸的一种简捷、高效、经济的实验方法，为日后的大量生产提供可靠地实验数据。并为新生儿氨基酸代谢异常检测平台提供的建立提供物质基础和标准图谱。
[Abstract]:Objective to find a simple, rapid and effective method for the synthesis of deuterium amino acids, so as to reduce the cost and synthesize 伪 -deuterium amino acids according to the method, so as to establish a platform for the detection of abnormal amino acid metabolism in newborns. Methods the reaction temperature was investigated by heavy water exchange method as the synthesis method of deuterated amino acids. The effect of reaction time and exchange times on the synthesis of deuterated L-histidine.) based on the single factor experimental conditions of L- [伪-(24-2H _ 3)] -histidine, the response surface optimization experiment of L- [伪 ~ (24-2H _ 3)] -histidine was carried out using L- [伪 _ 24-2H _ 3] -histidine response surface as reference, according to the amino acid, base, amino acid, alkalinity, and the response surface of L- [伪 _ 24-2H _ 3] -histidine. Neutral selection of L- [伪 -2H] -glutamic acid and L- [伪 -2H] -methionine as response surface optimization experiment. 4) according to the optimized conditions of response surface, L- [伪 -2H] -proline L- [伪 -2H] glycine L- [伪 -2H] isocine and L- [伪 -2H] valine were synthesized in turn. The deuterium amino acids were measured by 1H-NMR and their deuterium rates were calculated. The configuration of deuterated amino acids was identified by circular dichroism and analyzed qualitatively by mass spectrometry. Results 1) the optimal conditions for the synthesis of L- [伪 -2H] -histidine by response surface method were as follows: reaction time 6.47 h, reaction temperature 185 鈩

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