Total Synthesis of Unsaturated Phosphatidylserine and its Activity in Clotting Systems

Abstract

NATURAL phosphatidylserine (PS) has been found to be a potent anticoagulant^1,2. We describe here the comparable activity of totally synthetic DL-α-(dioleoyl)-phosphatidyl-DL-serine. While synthetic distearoyl-phosphatidylserine was available earlier³, it was totally insoluble and could not be tested in clotting systems. The methyl ester of tert-butyloxy-carbonyl-dl-serine (BOC-serine)⁴ was treated with potassium hydroxide in methanol to give the salt, m.p. 206° (dec) (found: C, 39.52; H, 5.94; N, 6.14; C₈H₁₄NO₅K requires: C, 39.49; H, 5.80, N, 5.76), which on acidification gave a complex similar to that obtained from benzyloxycarbonyl-serine⁵. The complex had m.p. 102° (found: Neut. equiv., 450; C₈H₁₅O₅N. C₈H₁₄O₅NK requires 448.5). The complex was converted to the phthalimidomethyl ester of BOC-serine, m.p. 122°, in 73 per cent yield by treatment with phthalimidomethyl chloride⁶ in refluxing acetone (found: C, 55.86; H, 5.34; N, 7.53; C₁₇H₂₀N₂O₇ requires: C, 56.04; H, 5.53; N, 7.69). The other portion of the complex was recovered as the potassium salt of BOC-serine.