Synthesis of High Specific Activity [1-³H]-Farnesyl Pyrophosphate

The synthesis of tritiated farnesyl pyrophosphate with high specific activity is reported. E,E-Farnesol was oxidized to the corresponding aldehyde followed by reduction with lithium aluminium tritide (5% ³H) to give [1-³H]-E,E-farnesol. The specific radioactivity of the alcohol was determined from its triphenylsilane derivative, prepared under very mild conditions. The tritiated alcohol was phosphorylated by initial conversion to an allylic halide, and subsequent treatment of the halide with tris(tetra-n-butyl)ammonium hydrogen pyrophosphate. The hydride procedure followed in this work has advantages over existing methods for the synthesis of tritiated farnesyl pyrophosphate, giving a much higher radiochemical yield and offering the possibility of achieving theoretical specific activity levels when fully tritiated LiAlT₄ is employed.