利用Aldol反应合成新型同位素内标β-羟基-β-甲基丁酸钙-D  

Synthesis of New Isotope Internal Standard Calcium β-Hydroxy-β-methylbutyrate-D6 by Aldol Reaction

作　　者：郭会 陈武炼 GUO Hui;CHEN Wulian(Anpel Laboratory Technologies(Shanghai)Inc.,Shanghai 201600,China)

机构地区：[1]上海安谱实验科技股份有限公司,上海201600

出　　处：《合成化学》2025年第3期198-204,共7页Chinese Journal of Synthetic Chemistry

摘　　要：羟基-β-甲基丁酸钙作为食品添加物已得到广泛应用,为了准确检测该添加物在各种复杂食品基质中的含量,开发同位素稀释质谱法具有重要意义,而同位素内标是该方法所必需的基准物质。基于此背景,本文研究了一种新型同位素内标β-羟基-β-甲基丁酸钙-D6及其合成方法。以丙酮-D6作为同位素来源,与乙酸乙酯经过Aldol反应形成β-羟基-β-甲基丁酸乙酯-D6(1),再经过酯水解反应形成β-羟基-β-甲基丁酸-D6(2),最后和氧化钙成盐制成β-羟基-β-甲基丁酸钙-D6(3)。以消耗的乙酸乙酯计算化合物3的总产率可达80%。化合物3产品结构、纯度和氘同位素丰度经核磁共振波谱(NMR)、高效液相色谱(HPLC)和质谱(MS)表征确定,β-羟基-β-甲基丁酸钙-D6的化学纯度为98.68%,氘同位素丰度为99.86%D(原子分数),均高于98%,可为检测行业提供同位素内标,用于开发新的同位素稀释质谱法检测食品中β-羟基-β-甲基丁酸钙的含量,还可制定新的β-羟基-β-甲基丁酸钙的检测标准。Calcium β-hydroxy-β-methylbutyrate has been widely used as a food additive.It is important to develop isotope dilution mass spectrometry in order to accurately detect the content of this additive in various complex food matrices.The isotope internal standard is the necessary reference material for the method.Based on this background,the synthesis method of a new isotope internal standard,calcium β-hydroxy-β-methylbutyrate-D6(1),was investigated.The acetone-D6 was the source of the isotope deuterium.First,acetone-D6 and ethyl acetate undergo an Aldol reaction to form β-hydroxy-β-methylbutyrate ethyl ester-D6.Then through ester hydrolysis reaction to form β-hydroxy-β-methylbutyric acid-D6(2).Finally,calcium β-hydroxy-β-methylbutyrate-D6(3)was prepared by β-hydroxy-β-methylbutyric acid-D6 and calcium oxide.The yields of deuterium-labeled calcium β-hydroxy-β-methylbutyrate-D6 was 80%based on acetone-D6 consumed.The structure,chemical purity and deuterium isotopic enrichment of the product were identified by NMR,HPLC and MS to be the target compound.The chemical purity of calcium β-hydroxy-β-methylbutyrate-D6 was 98.68%,and the deuterium isotopic enrichment was 99.86%D(atom fraction).The chemical purity and deuterium isotopic enrichment were higher than 98%.It can provide an isotope internal standard for the detection industry to develop new isotope dilution mass spectrometry for the determination of calcium β-hydroxy-β-methylbutyrate content in food and establish a new detection standard for calcium β-hydroxy-β-methylbutyrate.

关 键 词：羟基-β-甲基丁酸钙 稳定同位素标记 ALDOL反应 合成 表征 

分 类 号：O628.11[理学—有机化学]