Analogs of natural lipids. III. Nonequivalence of methyl groups in methylated phospholipids

The dimethyl esters of a series of diastereoisomeric cyclopentanoid analogs of phosphatidic acid (A.J. Hancock, M.H. Stokes, and H.Z. Sable. 1977. J. Lipid Res. 18: 81-92.) have been studied by proton NMR spectroscopy at 60, 100, and 300 MHz. The signals of the P-O-CH3 protons near delta 3.80 show the expected doubling due to the 31P-1H coupling. In addition, the spectra of three of the isomers show additional multiplicity the line separation (in Hz) being proportional to the frequency of the spectrometer. This multiplicity is due to the nonequivalence of the two methoxyl groups on phosphorus, predictable from their diastereotopic nature. The same explanation is proposed for similar observations on other compounds made by other authors. The practical utility of symmetry considerations in lipid chemistry is discussed briefly.