目的:优化特利加压素还原烷基化条件,解决在还原烷基化时难以完全形成双烷基化产物及处理时间较长的问题.方法:以醋酸特利加压素原料为样品,以双烷基化特利加压素的相对峰面积为评价指标,优化还原反应中还原试剂的种类、还原试剂的浓度,还原温度和还原时间;优化烷基化反应中碘乙酰胺的浓度及烷基化时间.结果:选择三(2-羰基乙基)磷盐酸盐(TCEP)为还原试剂,最佳还原烷基化条件为:TCEP浓度为80mmol/L,还原温度为55℃,碘乙酰胺的浓度为120 mmol/L,还原烷基化总时间为5 min.结论:还原试剂种类、还原试剂浓度、还原温度、还原时间、碘乙酰胺浓度及烷基化时间是影响特利加压素还原烷基化转化率的关键参数,成功优化了特利加压素还原烷基化反应的条件,最佳条件下双烷基化的特利加压素相对峰面积可达97％,比优化前提高了 30％,反应总时间从40 min缩短至5 min.
Study on the reduction and alkylation conditions of terlipressin based on high-resolution mass spectrometry
Objective:To optimize the reductive alkylation conditions of terlipressin and solve the problems of difficulty in completely forming double alkylated products and long processing times during the reduction alkylation process.Methods:Terlipressin acetate was used as the sample,and the relative peak area of dialkylated terlipressin was used as the evaluation index to optimize the type,concentration,temperature,and time of the reducing reagents in the reduction reaction,as well as the concentration of iodoacetamide and alkylation time in the alkylation reaction.Results:Tri(2-carbonylethyl)phosphorus hydrochloride(TCEP)was selected as the reducing reagent.The optimum conditions for reductive alkylation were as follows:the concentration of 80 mmol/L,reduction temperature of 55 ℃,iodoacetamide concentration of 120 mmol/L,and total reductive alkylation time of 5 min.Conclusion:The type and concentration of the reducing agent,reducing temperature,reducing time,iodoacetamide concentration,and alkylation time are key parameters that affect the conversion rate of terlipressin reduction alkylation.The conditions of the terlipressin reduction alkylation were successfully optimized.Under optimum conditions,the relative peak area of terlipressin for double alkylation reached 97％,which was 30％higher than that before optimization,and the total reaction time was shortened from 40 min to 5 min.
terlipressin acetatedisulfide bondsreductive alkylationultra-high-resolution mass spectrometry
万方数据
维普
