Efficient Synthesis of Phospholipids from Glycidyl Phosphates

Abstract

New efficient routes to enantiopure phospholipids, starting from (S)-glycidol, are described. Lysophosphatidic acids and phosphatidic acids were obtained in good overall yields from (S)-glycidol, in only three and four steps, respectively. Moreover, the strategy can also be used to produce phosphatidylcholines in three steps. Using dialkylphosphoramidites, (S)-glycidol was phosphorylated to give (R)-1-O-glycidyl dialkyl phosphates. Regiospecific epoxide opening, using hexadecanol or cesium palmitate, followed by phosphate deprotection, provided lysophosphatidic acids. 2-O-Esterification prior to phosphate deprotection provided 1,2-O-diacyl and 1-O-alkyl-2-O-acyl phosphatidic acids. Phosphorylation of (S)-glycidol using phosphorus oxychloride followed by in situ treatment with choline tosylate produced (R)-glycidyl phosphocholine. Subsequent nucleophilic opening of the epoxide using cesium palmitate produced 1-O-palmitoyl-sn-glycero-3-phosphocholine, which has been used in syntheses of phosphatidylcholines.

Phosphorothioate Analogues of Alkyl Lysophosphatidic Acid as LPA3 Receptor‐Selective Agonists

“…The key carbonoxygen bond-forming step was a regio-and stereospecific nucleophilic opening of (R)-glycidyl tosylate 8 with a long-chain alcohol using BF 3 etherate as a catalyst. [23,24] As reported by Guivisdalsky and Bittman, epoxide opening of (R)-or (S)-glycidol toluenesulfonate with oleyl alcohol occurred exclusively at the C3 position, stereospecifically affording the ring-opened product in very high enantiomeric excess (97-99 % ee) as determined by HPLC on a chiral stationary phase. [25,26] Therefore, there is no loss of optical purity during the synthesis of the phosphorothioate LPA analogues.…”

Lack of stereospecificity in lysophosphatidic acid enantiomer‐induced calcium mobilization in human erythroleukemia cells

“…Analog L is, however, not included in the table because of its distinct structure. The LPA enantiomers and analogs D and G-J (98% ee, purity >95% by NMR) were synthesized according to previously published methods by starting from commercially available (R)-or (S)-glycidol (18). Analog K (98% ee, purity >95% by NMR) was synthesized by using the same procedure.…”

Chemo-enzymatic Synthesis of rac 1-O-Alkyl-2-acetyl-sn-glycero-3-phosphocholine and its Analogues

“…They have used -diisopropyl tartarate and -diisopropyl tartarate as substrate, followed by in situ derivitization. Regiospecific opening of epoxide, followed by several steps to yield PAF using crown ethers was also carried out 24 . The synthesis involved a total of 6 steps with 75 yield.…”