Synthesis of conformationally restricted acidic lipids. I. Cyclopentanoid analogs of phosphatidylserine

A series of six analogs of phosphatidylserine (PS) was synthesized in which the conformational mobility of the backbone was limited. Each analog was a derivative of one of the three diastereoisomeric cyclopentane-1,2,3-triols, so that the glycerol moiety of the PS was, in effect, replaced by each cyclopentane-1,2,3-triol. Four of the members of the series were vicinal dipalmitates [1,2/3-(1P); 1,2/3-(3P); 1,2,3/0-(1P); 1,3/2-(1P)] while the other two members were "unnatural" in that they contained a 2-phosphate group. The two 2-phosphate derivatives were meso-forms and each of the other four derivatives was a DL-pair. Each PS analog was obtained as a stable microcrystalline precipitate analyzing for the monohydrate of a mixture of mono- and di-sodium salts. The infrared spectra, melting behavior, and chromatographic mobility of each sodium salt mixture resembled those obtained for bovine (glycero-)-phosphatidyl-L-serine; the stereochemical differences in the ring caused only marginal variation in these properties. The optical rotation values of the compounds varied with the stereochemistry of the ring. The all-trans-2-phosphate isomer 8d exhibited a negative rotation value, in contrast to each of the other isomers. The all-trans isomer [1,3/2-(1P)] was shown to undergo diazometholysis with diazomethane to give the dimethyl ester of cyclopentano-phosphatidic acid.