3-氯-1,2-丙二醇棕榈酸双酯单体制备及对映体稳定性分析

Preparation of 3-monochloropropane-1,2-diol ester enantiomer and analysis of enantiomer stability

中文关键词:  3-氯-1,2-丙二醇棕榈酸双酯，溶剂稳定性，单体制备

英文关键词:3-monochloropropane-1,2-diol esters  solvent stability  monomer preparation

中文摘要:

      目的 建立3-氯-1,2-丙二醇棕榈酸双酯(3-monochloropropane-1,2-diol esters, 3-MCPDE)对映体高纯度手性单体制备方法, 并系统研究3-MCPDE对映体在有机溶剂中的稳定性特征。方法 利用制备型高效液相色谱, 以ChiralCore Amy-Z手性柱(10 mm×250 mm, 5 μm)为分离柱, 乙醇为流动相进行等度洗脱, 实现3-MCPDE对映体的制备分离; 采用超高效合相色谱-串联质谱法(ultra performance convergence chromatography-tandem mass spectrometry, UPC2-MS/MS)评估3-MCPDE对映体在异丙醇、甲醇、乙腈、正己烷和乙醇5种溶剂中, 于不同温度(4 ℃与25 ℃)与光照条件下储存42 d的稳定性; 通过降解动力学曲线计算降解率与对映体分数, 分析温度与光照的影响规律。结果 成功制备纯度大于等于95%的3-MCPDE手性单体。稳定性研究表明, 3-MCPDE在所有溶剂中均发生降解, 降解率依次为: 乙醇>正己烷>异丙醇>乙腈>甲醇; 降解过程呈双相特征, 包括0~24 h的快速降解阶段及后期缓慢衰减阶段; 温度是影响降解的关键因素, 25 ℃下降解普遍高于4 ℃; 光照在甲醇、乙醇等极性溶剂中促进作用更明显; 所有条件下两对映体降解行为一致, 对映体分数始终为0.50, 未出现立体选择性现象。结论 本研究揭示了3-MCPDE对映体在不同溶剂中的非立体选择性降解规律, 建立了高效的手性单体制备方法, 推荐将标准品置于甲醇中4 ℃避光保存。研究结果为开展对映体水平的安全性评估提供了方法支持, 对深入解析3-MCPDE手性单体的毒理机制具有重要意义。

英文摘要:

      Objective To establish a method for preparing high-purity chiral monomers of 3-monochloropropane-1,2-diol esters (3-MCPDE) and systematically study the stability characteristics of 3-MCPDE enantiomers in organic solvents. Methods Using preparative high performance liquid chromatography with a ChiralCore Amy-Z chiral column (10 mm×250 mm, 5 μm) as the separation column and ethanol as the mobile phase for isocratic elution, the preparative separation of 3-MCPDE enantiomers was achieved. The stability of 3-MCPDE enantiomers stored for 42 d in 5 kinds of solvents (isopropanol, methanol, acetonitrile, n-hexane and ethanol) under different temperatures (4 °C and 25 °C) and light conditions was evaluated using ultra performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS). Degradation rates and enantiomer fraction values were calculated from degradation kinetic curves to analyze the influence patterns of temperature and light. Results Successfully prepared chiral monomer 3-MCPDE with a purity of 95% or higher. Stability studies showed that 3-MCPDE underwent significant degradation in all solvents, with degradation rates in the order: ethanol>n-hexane>isopropanol>acetonitrile>methanol. The degradation process exhibited a typical biphasic pattern, consisting of a rapid degradation phase within 0–24 h followed by a slower attenuation phase. Temperature was a key environmental factor affecting the degradation rate, with generally higher degradation at 25 °C than at 4 °C. Light exposure showed a more pronounced promoting effect in polar solvents like methanol and ethanol. Under all experimental conditions, the degradation behaviors of the 2 enantiomers were highly consistent, with the enantiomer fraction value consistently remaining at 0.50, indicating no stereoselective phenomenon was observed. Conclusion This study reveals the non-stereoselective degradation pattern of 3-MCPDE enantiomers in different solvents, establishes an efficient method for the preparation of chiral monomers, and recommends storing the standards in methanol at 4 °C in the dark. These findings provide methodological support for enantiomer-level safety assessment and are of great significance for in-depth elucidation of the toxicological mechanisms of 3-MCPDE chiral monomers.