Journal of Lipid Research, Vol 26, 623-628, Copyright © 1985 by Lipid Research, Inc.
Synthesis of phosphatidylcholine analogs with an alkyl group at C1 or C3 of the glycerol moiety
NM Witzke and R Bittman
The syntheses of 1,2-di-(O-hexadecyl)-rac-glycero-3-phosphocholines
containing a methyl group at either C1 or C3 of the glycerol moiety are
described. The methyl group was introduced at C1 in a synthetic scheme
beginning with the hydroxylation of methyl vinyl ketone. The primary
hydroxyl was protected by tritylation and the carbonyl group was reduced
with sodium borohydride. Di-O-alkylation with 1-bromohexadecane was
accomplished using finely powdered potassium hydroxide in refluxing
toluene. Detritylation afforded two diastereomers of 2,3-di-(1-
hexadecyloxy)butanol. Reaction with the simple phosphorylating agent,
dimethylphosphoryl chloride (Bittman, R., A. F. Rosenthal, and L. A.
Vargas. 1984. Chem. Phys. Lipids. 34: 201-205), followed by conversion to
the phosphatidic acid and condensation with choline tosylate in the
presence of trichloroacetonitrile afforded the diastereomers of 1-
methyl-1,2-di-(O-hexadecyl)-rac-glycero-3-phosphocholine. The analog
bearing a methyl group at C3 was prepared in a synthetic scheme beginning
with the hydroxylation of acrolein dimethyl acetal. After di- O-alkylation
with 1-bromohexadecane and sodium hydride in dimethyl sulfoxide/toluene,
the acetal was converted to the aldehyde. Reaction with methylmagnesium
bromide afforded the diastereomers of 1,2-di-(1- hexadecyloxy)-3-butanol,
which were converted to the phosphocholine derivatives. These diether
phosphatidylcholine analogs may be useful for investigating the effect of
steric bulk at C1 and C3 of the glycerol moiety on the interactions with
membrane components.
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