Large-scale total synthesis of 13C3-labeled citrinin and its metabolite dihydrocitrinone
Large-scale total synthesis of 13C3-labeled citrinin and its metabolite dihydrocitrinone
复制标题
DOI：
10.1007/s12550-018-0308-3
复制
发表时间：
2018-05-01
影响因子：
3
通讯作者：
Humpf, Hans-Ulrich
中科院分区：
文献类型：
--
作者：
Bergmann, Dominik;Huebner, Florian;Humpf, Hans-Ulrich
食品、饲料和生理样品中肾毒性真菌毒素的分析仍然具有挑战性。目前，液相色谱联用质谱法是实现低检测限的首选方法。但是矩阵效应会对这种方法造成损害。稳定同位素稀释分析可以防止这些问题的发生。为此，大规模合成了一种用于稳定同位素稀释分析的柑桔苷稳定同位素标记标准品。改进的非对映选择性全合成策略提供了通过邻甲苯磺酸阴离子化学分两步引入三个c -13标签的可能性。这导致了3 Da的质量差，足以防止光谱重叠。此外，以相同的质量差合成了一种稳定的同位素标记形式的二氢柠檬酸酮（柠檬酸苷的主要尿液代谢物）。这是通过一系列环化、氧化、脱保护和羧基化反应实现的，这些反应从标记柠檬黄蛋白合成的受保护中间体开始。因此，该方法也为柑桔素大规模合成二氢柑桔酮提供了一条完整的途径。
The analysis of the nephrotoxic mycotoxin citrinin in food, feed, and physiological samples is still challenging. Nowadays, liquid chromatography coupled with mass spectrometry is the method of choice for achieving low limits of detection. But matrix effects can present impairments for this method. Stable isotope dilution analysis can prevent some of these problems. Therefore, a stable isotopically labeled standard of citrinin for use in stable isotope dilution analysis was synthesized on large scale. The improved diastereoselective total synthetic strategy offered the possibility to introduce three C-13-labels in two steps by ortho-toluate anion chemistry. This led to a mass difference of 3 Da, sufficient for preventing spectral overlap. Additionally, a stable isotopically labeled form of dihydrocitrinone, the main urinary metabolite of citrinin, was synthesized with the same mass difference. This was achieved by a sequence of cyclisation, oxidation, deprotection, and carboxylation reactions starting from a protected intermediate of the labeled citrinin synthesis. Thus, this method also offers a complete way to synthesize dihydrocitrinone from citrinin on large scale.