Analogs of natural lipids. IV. Synthesis and properties of cyclopentanoid analogs of phosphatidic acid1

A new series of phosphatidic acid analogs has been synthesized in which the glycerol moiety of diacylglycerophosphoric acid is replaced by each of the three isomeric cyclopentane-1,2,3-triols (1,3/2, DL-1,2/3, and 1,2,3/0). Of the seven possible configurational and positional phosphatidic acid analogs of this series, five isomers have been obtained and characterized by spectroscopic methods and microanalysis. Four of the five isomers are 1-(or 3-)phosphoryl derivatives, while the fifth is a 2-phosphate. The analogs were prepared in configurationally pure form by unequivocal synthetic procedures involving selectively blocked intermediates: acyl migration was avoided by the use of mild deblocking procedures. The anhydrous lipid products, all of which are dipalmitoyl esters, are solids indefinitely stable at room temperature in the free acid or potassium salt form; they have chromographic mobility and melting points similar to dipalmitoyl glycerophosphoric acid the dipotassium salts bind water of hydration tenaciously, remaining hydrated after drying in vacuo at 100°C. NMR spectra of dimethyl esters of some of the analogs show nonequivalence of the two methyl groups, consistent with the diastereotopic nature of those groups. In addition to their intrinsic interest as conformationally restricted acidic lipids, the analogs are now available as starting materials for the synthesis of the more complex acidic and amphoteric lipids required for our exploitation of these cyclopentanoid analogs as unique probes for the study of lipid–lipid and protein–lipid interactions.