A facile asymmetric synthesis of glycerol phospholipids via tritylglycidol prepared by the asymmetric epoxidation of allyl alcohol. Thiolester and thioether analogs of phosphatidylcholine.
Trityl-glycidol was synthesized by in situ derivatization of glycidol, which was prepared by the catalytic asymmetric epoxidation of allyl alcohol. Depending on the enantiomer of diisopropyl tartrate used with the titanium catalyst, either (R)- or (S)-trityl-glycidol was obtained in a "one pot" synthesis in about 50% overall yield. The optical purity, determined by NMR spectroscopy of a Mosher ester, was greater than 98% ee. Nucleophilic opening of the chiral epoxide with dodecyl mercaptan gave optically active 1-S-dodecyl-3-O-trityl-1-thio-glycerol, which was used to synthesize 1-S-dodecyl-2-O-decanoyl-thio-sn-glycero-3-phosphocholine. Opening of the epoxide with methyl xanthate gave a 1,2-trithiocarbonate derivative of trityl glycerol which can be used to synthesize 1,2-bis(S-decanoyl)-1,2-dithio-sn-glycero-3-phosphocholine. Opening of the epoxide with thiodecanoic acid gave 1-S-decanoyl-3-O-trityl-1-thio-glycerol which was used to synthesize 1-S-decanoyl-2-O-decanoyl-1-thio-sn-glycero-3-phosphocholine.
Hendrickson
H S
HS
Department of Chemistry, St. Olaf College, Northfield, MN 55057.
Hendrickson
E K
EK
D004852:Epoxy Compounds; D004952:Esters / Q000138:chemical synthesis; D005995:Glyceryl Ethers / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000138:chemical synthesis; D010743:Phospholipids / Q000138:chemical synthesis*; D020005:Propanols; D013440:Sulfides / Q000138:chemical synthesis; D014320:Triphenylmethyl Compounds
D004852:Epoxy Compounds; D004952:Esters; D005995:Glyceryl Ethers; D010713:Phosphatidylcholines; D010743:Phospholipids; D020005:Propanols; D013440:Sulfides; D014320:Triphenylmethyl Compounds; C006463:allyl alcohol; C004312:glycidol