SYSTHESIS OF ENANTIOMERIC a-BISPHOSPHATIDIC ACIDS

In 1941 Pangborn (1) reported the isolation of a complex phosphatidic acid from beef heart and suggested the name cardiolipin for it. The presence of this phospholipide seems to be essential for the complementbinding activity of beef heart extracts with sera of syphilitic patients. On hydrolysis (2) with ethanolic potassium hydroxide at room temperature the phosphatidic acid yielded, in addition to linoleic acid and oleic acid, a polyester of glycerophosphoric acid, which on further hydrolysis with hot dilute mineral acid readily formed glycerophosphoric acid and glycerol. The analytical values of the barium salt of the polyester seemed to agree best with those calculated for the barium salt of glyceryl tri(glycerophosphate) and led Pangborn to propose tentatively structure I for cardiolipin. In 1948 Fleury (3,4) reported that egg lecithin on hydrolysis with methanolic potassium hydroxide at room temperature forms a polymeric glycerophosphoric acid (glyc6rophosphatogtbze) which resembles Pangborn’s polyester in that it is incapable of forming an insoluble lead salt, and, on hydrolysis with hot dilute mineral acid, yields glycerophosphoric acid. The structure assigned to this compound by Fleury and le Dizet (5) was similar to that proposed by Pangborn for the fatty acid-free skeleton of cardiolipin. 2 years later the present author and Kates (6) made the observation that the synthetic and undoubtedly monomolecular L-a-(dipalmitoyl) lecithin (7) on hydrolysis with methanolic potassium hydroxide at 37” yields an organic phosphate which resembles Pangborn’s and Fleury’s polyesters in that it is also incapable of forming an insoluble lead salt. These observations appear to indicate that the structure of the cardiolipin may not be as complex as the degradation product obtained with ethanolic potassium hydroxide suggests, and a reinvestigation of the cardiolipin structure seems desirable. That phosphatidic acids of less complex structure can possess a cardiolipin-like activity was shown recently by Faure (8), who found that the phosphatidic acids of cabbage, carrots, peas, and peanuts are active as haptens in the Wassermann reaction, although their activity is weaker than that of cardiolipin. These phosphatidic acids are unsaturated and in general possess the simple structure shown by formula II. It seems, however, that the phosphatidic acids do not have to be unsaturated to be