Hickey Michael J, Lindqvist Johnny, Ha Young-Hwan, Andersson Håkan, Elmore Charles S
Early Chemical Development, Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
Translational Biomarker & Bioanalysis, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.
J Labelled Comp Radiopharm. 2019 Sep;62(11):695-706. doi: 10.1002/jlcr.3714. Epub 2019 May 7.
Di-docosahexaenoyl (C22:6)-bis(monoacylglycerol) phosphate (BMP) has been identified as a promising biomarker for drug-induced phospholipidosis (DIPL). Both unlabelled and stable isotope labelled versions of BMP were desired for use as internal standards. Isopropylideneglycerol was converted to 4-methoxyphenyldiphenylmethyl-3-PMB-glycerol in three steps. Initially, the 2-postion of the glycerol was protected as a t-butyldiphenylsilyl ether, which proved to be a mistake; deprotection of the ether resulted in the decomposition of the compound. A switch to a t-butyldimethylsilyl ether protecting group resulted in an intermediate that could be deprotected to the alcohol to give the target compound after salt exchange. The same procedure was used to prepare [ C ]BMP from [ C ]glycerol.
二十二碳六烯酰基（C22:6）-双（单酰甘油）磷酸酯（BMP）已被确定为药物性磷脂沉积症（DIPL）的一种有前景的生物标志物。未标记和稳定同位素标记的BMP版本都被用作内标。异丙叉甘油分三步转化为4-甲氧基苯基二苯基甲基-3-PMB-甘油。最初，甘油的2-位被保护为叔丁基二苯基甲硅烷基醚，事实证明这是一个错误；该醚的脱保护导致化合物分解。改用叔丁基二甲基甲硅烷基醚保护基团得到一种中间体，该中间体可以脱保护为醇，经盐交换后得到目标化合物。用同样的方法从[C]甘油制备[C]BMP。
