Scalable Synthesis and Purification of Acetylated Phosphatidyl Choline Headgroup

Abstract

The acetylated headgroup of the most abundant mammalian phospholipid, 1,2-diacetyl-3-sn-phosphatidyl choline (DAcPC), has several important applications in research. For instance, it can be dissolved in the same amount of water as in the fluid PC bilayer, to create a surrogate of a PC headgroup stratum, for studying solvation of small molecules and the influence of their structure on the process. In contrast to PC derivatives with longer acyl chains, DAcPC does not self-aggregate, rendering the aqueous solution homogeneous and suitable for simplified analyses of interactions of molecules with the headgroups. Several studies have been published where DAcPC was used in a crudely purified form. Here we describe a one-step preparation of DAcPC from commercially available bulk chemicals and purification of the product by crystallization and washing. The process gives a good yield and is easily scalable. The availability of enantiopure, crystalline DAcPC could open the door to more extensive biochemical, pharmacological, and nutritional studies of this interesting chemical.

Keywords: PC bilayer; PC headgroup stratum surrogate; bilayer accumulation; bilayer transport; drug solvation in headgroup stratum; drug-headgroup interactions; phosphatidyl choline (PC) headgroup.

Scheme 1

Retrosynthetic analysis of PC derivatives. The R₁ and R₂ substituents may be identical.

Scheme 2

DAcPC synthesis from GPC using Ac₂O and DIPEA.