Unified synthesis of DSPC and PSPC: Chemical entities of hydrogenated soy L-α-phosphatidylcholine (HSPC), a key component of liposomal drug formulations

Abstract

A simple, unified and scalable strategy, emanating from the readily available chiral pool d-solketal, has been employed to obtain the enantiomerically pure components of hydrogenated soy L-α-phosphatidylcholine (HSPC), namely distearoyl phosphatidylcholine (DSPC) and 1-palmitoyl-2-stearoyl-phosphatidylcholine (PSPC). HSPC is obtained by hydrogenating naturally occurring soy L-α-lecithin; this affords a glycerophospholipid mixture containing C-16 (minor) or C-18 (major) fatty acid chain at sn-1, C-18 chain at sn-2 position and phosphatidylcholine at sn-3 position. HSPC already has numerous applications as an excipient and essential component in many FDA approved liposomal drug formulations such as Doxil® (doxorubicin HCl liposome injection) and AmBisome® (amphotericin B liposome injection). However, there is increasing interest in uncovering the potential individual applications of its components, DSPC and PSPC, too. In this context, the current synthesis offers a strategy to have a ready bespoke access to multi-gram quantities of DSPC and PSPC (in particular) that does not rely on tedious separation of the components of HSPC.