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目的 寻找氘代氨基酸简便有效的合成方法.方法 反应温度、反应时间和交换次数单因素实验探索合成L-[α, 2, 4-2H3]-组氨酸-d3;以单因素实验结果为参考进行合成L-[α, 2, 4-2H3]-组氨酸-d3的响应面法优化;应用微波法合成L-[α, 2, 4-2H3]-组氨酸-d3.结果 ①响应面优化L-[α, 2, 4-2H3]-组氨酸-d3的条件是:反应时间6.47 h, 反应温度185℃, 交换次数3次;②相同时间和反应温度, 微波合成两次即可达到氘代率98%以上.结论 通过响应面实验对重水交换法优化合成L-[α, 2, 4-2H3]-组氨酸-d3, 得出最优实验条件, 最终提高了产率.“,”Objective To find a simple and effective method for the synthesis of deuterate amino acids.Methods Single factor experiment including reaction temperature, reaction time and exchange times which was used to exlpore the synthesis of L-[α, 2, 4-2H3]-histidine-d3;The results of single factor experiments were taken as a reference and the response surface methodology was used to synthesize L-[α, 2, 4-2H3]-histidine-d3 was optimized;Microwave method was used to synthesize L-[α, 2, 4-2H3]-histidine-d3.Results ①The condition of response surface optimization of L-[α, 2, 4-2H3]-histidine-d3 included that the reaction time was set at 6.47 hours, the reaction temperature was controlled at 185 ℃, exchanged for 3 times;②The deuterium rate was increased to 98% or more under the condition of the microwave synthesis method with the same time and the same temperature.Conclusion The synthesis of L-[α, 2, 4-2H3]-histidine-d3 by heavy water exchange method can carry out by response surface experiment, and the optimal experimental is obtained.The production rate is high.