Synthesis of Plasmalogen via 2,3-Bis-O-(4‘-methoxybenzyl)-sn-glycerol

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The synthesis of the O -vinyl ether phospholipid plasmalogen 1 from 2,3-bis- O -[ p -methoxybenzyl (PMB)]- sn -glycerol ( 13 ) is described. Treatment of 13 with potassium hydride, trichloroethylene, and n -butyllithium gave a 1- O -alkynyl glycerol derivative, which was alkylated with 1-iodohexadecane to afford the long-chain O -alkynyl ether 14 . The latter was quantitatively converted to cis -enol ether 15 ( Z/E ratio between 35:1 and 100:1) with Lindlar catalyst in hexane/EtOAc 1:1 containing quinoline. The PMB groups of 15 were removed by Birch reduction (Na, NH 3 ), giving 1- O -[1‘-( Z )-octadecenyl]- sn -glycerol ( 2 ) in 95% yield. Regioselective silylation of 2 followed by palmitoylation provided 1- O -[1‘-( Z )-octadecenyl]-2- O -palmitoyl-3-( tert -butyldiphenylsilyl)- sn -glycerol ( 17 ). Desilylation with Bu 4 NF/imidazole at −23 °C followed by phosphocholine insertion (using 2-chloro-2-oxo-1,3,2-dioxaphospholane with 2 equiv of pyridine in benzene at 4 °C and then trimethylamine in benzene/MeCN 1:3 at 70 °C) completes the synthesis of plasmalogen ( 1 ).