A Modular Synthesis of Alkynyl-Phosphocholine Headgroups for Labeling Sphingomyelin and Phosphatidylcholine

摘要

A general route to phospho- and sphingolipids that incorporate an alkyne in the phosphocholineheadgroup is described. The strategy preserves the ammonium functionality of the phosphocholineand can be easily modified to introduce desired functional groups at the N-acyl chain. The targetsaccessible with this strategy provide a bioorthogonal handle for postsynthetic introduction offluorophores or other labeling agents with aqueous phase chemistry. We report the synthesis ofsphingomyelin derivatives that incorporate a fluorophore and an alkyne. The modified sphingolipidsretain activity as substrates for sphingomyelinase, making these compounds viable probes ofenzymatic activity. Importantly, the strategy allows modification of the lipid across the phospho-diester, making the alkyne a potential probe of sphingomyelinase activity.