Efficient synthesis of phospholipids from glycidyl phosphates.
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.
Lindberg
Jan
J
Department of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
Ekeroth
Johan
J
Konradsson
Peter
P
D004852:Epoxy Compounds / Q000737:chemistry*; D010743:Phospholipids / Q000138:chemical synthesis*; D010766:Phosphorylation; D020005:Propanols / Q000737:chemistry; D013237:Stereoisomerism
D004852:Epoxy Compounds; D010743:Phospholipids; D020005:Propanols; C004312:glycidol