Synthesis of di‐docosahexaenoyl (C22:6)‐bis(monoacylglycerol) phosphate in unlabelled and C‐13 labelled forms for use as a biomarker of drug induced phospholipidosis

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 ¹³C₆]BMP from ¹³C₃]glycerol.