Synthesis of enantiomerically pure 1-O-phosphocholine-2-O-acyl-octadecane and 1-O-phosphocholine-2-N-acyl-octadecane.
This is the first report on the chemical synthesis of enantiomerically pure R- or S-1-O-phosphocholine-2-O-acyl-octadecanes and R- or S-1-O-phosphocholine-2-N-acyl-octadecanes. From a structural point of view these phospholipids are intermediates between phosphatidylcholine and sphingomyelin. The synthesis of these model compounds is based on R- or S-1.2-O-isopropylidene-glyceraldeyde for chain elongation in a Wittig reaction with pentadecane-triphenylphosphine bromide. The resulting 1.2-O-isopropylidene-octadec-3-en is converted to R- or S-1.2-octadecanediol by catalytic hydrogenation of the double bond and by acidic removal of the isopropylidene protecting group. Tritylation of R- or S-1.2-octadecanediol results in the general intermediates R- or S-1-O-trityl-2-hydroxy-octadecane. These are the key intermediates for the synthesis of the phosphatidylcholine- or sphingomyelin-like end products. R- or S-1-O-phosphocholine-2-O-acyl-octadecane is obtained from the tritylated intermediates via benzylation in position 2, acidic detritylation and conversion of the R- or S-1-hydroxy-2-benzyl-octadecanes to the respective phosphocholines via the phosphoethanolamines. Catalytic hydrogenolysis of the benzyl group results in R- or S-1-O-phosphocholine-2-hydroxy-octadecane, which is converted to the phosphatidylcholine-like end products by acylation. R- or S-1-O-phosphocholine-2-N-acyl-octadecane is obtained from the tritylated intermediate by conversion of the R- or S-2-hydroxy group into the N-phthalimido group, which is achieved by inversion of the configuration using the Mitsunobu reaction with phthalimid. After acidic detritylation, the product is converted to the respective S- or R-1-O-phosphocholine derivative in a similar sequence of reactions. The phthalimido group is converted to the 2-amino group, and acylation results in the sphingomyelin-like end products.
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Department 145, Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
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D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008567:Membranes, Artificial; D008956:Models, Chemical; D015394:Molecular Structure; D010713:Phosphatidylcholines / Q000138:chemical synthesis / Q000737:chemistry; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors; D013109:Sphingomyelins / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010743:Phospholipids; D013109:Sphingomyelins; D010741:Phospholipases A; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase