Xu Yong, Prestwich Glenn D
Department of Medicinal Chemistry and Center for Cell Signaling, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, Utah 84108-1257, USA.
J Org Chem. 2002 Oct 4;67(20):7158-61. doi: 10.1021/jo0203037.
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.
溶血磷脂酸（LPA，1-或2-酰基-sn-甘油-3-磷酸）是一种由活化血小板和卵巢癌细胞产生的重要磷脂介质。由于在生理条件下，容易发生的酰基迁移会导致1-或2-酰基物种的混合物达到平衡，这阻碍了通过G蛋白偶联受体理解LPA信号传导的努力。我们描述了一种从D-甘露糖醇1,2:5,6-双丙酮化物出发，获得对映体纯的溶血磷脂类似物的新的有效途径，得到了(2R)-酰基-sn-甘油-3-磷酸的两种1,1-二氟脱氧类似物。这些化合物是不稳定的sn-2 LPA物种的迁移阻断类似物。二氟甲基非对映异位氟的(19)F NMR显示出意想不到的溶剂依赖性。
