Synthesis of optically active 1-acyl-2-O-alkyl-sn-glycero-3-phosphocholine via 1-O-benzyl-sn-glycerol 3-arenesulfonate.
A stereocontrolled route to 1-palmitoyl-2-O-hexadecyl-sn-glycero-3-phosphocholine from (R)-glycidyl tosylate is described. This method gives very high enantioselectivity (93-96% enantiomeric excess) and can be used to prepare 3-acyl-2-O-alkyl-sn-glycero-1-phosphocholines from (S)-glycidyl tosylate. The key step is the preparation of 1-O-benzyl-sn-glycerol 3-tosylate by the boron trifluoride etherate catalyzed regio- and stereo-specific opening of the epoxide ring with excess benzyl alcohol. The alkyl group is introduced using alkyl trifluoromethanesulfonate in the presence of excess 2,6-di-tert-butyl-4-methylpyridine. Debenzylation gives 2-O-alkyl-sn-glycerol 3-arenesulfonate, which is acylated and then converted into the phosphocholine. The use of chiral glycidyl derivatives as starting materials for the synthesis of glycerophospholipids is discussed.
Ali
S
S
Department of Chemistry, Queens College, City University of New York, Flushing 11367.
Bittman
R
R
D055598:Chemical Phenomena; D002621:Chemistry; D005990:Glycerol / Q000031:analogs & derivatives*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010743:Phospholipids / Q000138:chemical synthesis*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013451:Sulfonic Acids
C029271:O-deacetyl platelet activating factor; D010743:Phospholipids; D010972:Platelet Activating Factor; D013451:Sulfonic Acids; D005990:Glycerol