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.

ABSTRACT

Di-docosahexaenoyl (C226)-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 [13 C6 ]BMP from [13 C3 ]glycerol.