Synthesis of Phosphatidyl Glycerol Containing Unsymmetric Acyl Chains Using H-Phosphonate Methodology
Zachary J. Struzik,
Shruti Biyani,
Tim Grotzer,
Judith Storch,
David H. Thompson
Affiliations
Zachary J. Struzik
Bindley Bioscience Center, Department of Chemistry, Multi-Disciplinary Cancer Research Facility, Purdue University, 1203 W. State Street, West Lafayette, IN 47907, USA
Shruti Biyani
Bindley Bioscience Center, Department of Chemistry, Multi-Disciplinary Cancer Research Facility, Purdue University, 1203 W. State Street, West Lafayette, IN 47907, USA
Tim Grotzer
Bindley Bioscience Center, Department of Chemistry, Multi-Disciplinary Cancer Research Facility, Purdue University, 1203 W. State Street, West Lafayette, IN 47907, USA
Judith Storch
Department of Nutritional Sciences and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA
David H. Thompson
Bindley Bioscience Center, Department of Chemistry, Multi-Disciplinary Cancer Research Facility, Purdue University, 1203 W. State Street, West Lafayette, IN 47907, USA
Naturally occurring phospholipids, such as phosphatidyl glycerol (PG), are gaining interest due to the roles they play in disease mechanisms. To elucidate the metabolism of PG, an optically pure material is required, but this is unfortunately not commercially available. Our previous PG synthesis route utilized phosphoramidite methodology that addressed issues surrounding fatty acid substrate scope and glycerol backbone modifications prior to headgroup phosphorylation, but faltered in the reproducibility of the overall pathway due to purification challenges. Herein, we present a robust pathway to optically pure PG in fewer steps, utilizing H-phosphonates that features a chromatographically friendly and stable triethyl ammonium H-phosphonate salt. Our route is also amendable to the simultaneous installation of different acyl chains, either saturated or unsaturated, on the glycerol backbone.
