Synthesis of a photoactivatable (2S,3R)-sphingosylphosphorylcholine analogue

The receptor for the lipid mediator sphingosylphosphorylcholine (SPC) has not yet been identified. We describe here the synthesis of the first photoaffinity analogue of SPC. This probe, which contains a C-14-isotopic label in the choline methyl groups and a photoreactive benzophenone in the long-chain base, may be a useful tool in the identification of the G protein coupled receptors that have been postulated to interact directly and specifically with SPC and in the definition of the ligand-binding sites. The key steps in the synthesis are selective reduction of the triple bond in enyne 6 to install the 4E double bond, Suzuki coupling to incorporate the benzophenone photophore at the end of the sphingoid chain, and reduction of the 2-azidoethyl phosphate headgroup of 13 followed by NNN-trimethylation to introduce the radiolabel into the choline moiety. The synthesis was completed by the release of the amino group at C2 of the sphingoid base of SPC analogue 2.