Efficient synthesis of the cholinephosphate phospholipid headgroup.
In search of an efficient method to prepare cholinephosphate headgroups in phospholipids under mild conditions (where the diacylglycerol moiety is not subject to oxidation), a method was developed for phosphorylation using a trialkyl phosphite and I2. The active intermediate is a phosphoryl iodide formed by oxidation of the phosphite with I2. 2-Bromoethanol, dimethyl chlorophosphite, and an alcohol (diglyceride) are converted to a phosphate triester in a one-pot reaction with high yield. In the second reaction, the phosphate triester is demethylated, and the ethyl bromide group is converted to choline by treatment with aqueous trimethylamine. This procedure is applied to the synthesis of hexadecylphosphocholine, and 1,2-didecanoyl-1-deoxy-1-thio-sn-glyceryo-3-phosphocholine.
Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA.
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D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry*; D010767:Phosphorylcholine / Q000138:chemical synthesis*
D010743:Phospholipids; D010767:Phosphorylcholine