Concise synthesis of acyl migration-blocked 1,1-difluorinated analogues of lysophosphatidic acid.
Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) is an important phospholipid mediator produced by activated platelets and by ovarian cancer cells. Efforts to understand LPA signaling through G-protein-coupled receptors are hampered by the facile acyl migration that results in equilibration to a mixture of the 1- or 2-acyl species under physiological conditions. We describe a new and efficient route to enantiomerically homogeneous lysophospholipid analogues from D-mannitol 1,2:5,6-bis-acetonide to give two 1,1-difluorodeoxy analogues of (2R)-acyl-sn-glycerol 3-phosphate. These compounds are migration-blocked analogues of the labile sn-2 LPA species. The (19)F NMR of diastereotopic fluorines of the difluoromethyl group shows an unexpected solvent dependence.
D020650:Combinatorial Chemistry Techniques; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis*; D008246:Lysophospholipids / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008353:Mannitol / Q000737:chemistry*; D015394:Molecular Structure; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D013237:Stereoisomerism
D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D008246:Lysophospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D008353:Mannitol