Synthesis of plasmalogen via 2,3-bis-O-(4 '-methoxybenzyl)-sn-glycerol

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 wi th potassium hydride, trichloroethylene, and n-butyllithium gave a 1-O-alky nyl glycerol derivative, which was alkylated with 1-iodohexadecane to affor d the long-chain O-alkynyI ether 14. The latter was quantitatively converte d to cis-enol ether 15 (Z/E ratio between 35:1 and 100:1) with Lindlar cata lyst in hexane/EtOAc 1:1 containing quinoline. The PMB groups of 15 were re moved by Birch reduction (Na, NH,), giving 1-O-[1'-(Z)-octadecenyl]-sn-glyc erol (2) in 95% yield. Regioselective silylation of 2 followed by palmitoyl ation provided 1-O-[1'-(Z)-octadecenyl]-2-O-palmitoyl-3-(tert-butyldiphenyl silyl)-sn-glycerol (17). Desilylation with Bu4NF/imidazole at -23 degrees C followed by phosphocholine insertion (using 2-chloro-2-oxo-1,3,2-dioxaphos pholane with 2 equiv of pyridine in benzene at 4 degrees C and then trimeth ylamine in benzene/MeCN 1:3 at 70 degrees C) completes the synthesis of pla smalogen (I).