Synthesis of a tritium labeled photolabile analogue of farnesyl diphosphate: (E, E)-[1-3H]-(2-diazo-3-trifluoropropionyloxy)geranyl diphosphate (DATFP-GDP)

Tritiated (E, E)-(2-diazo-3-trifluoropropionyloxy)geranyl diphosphate (DATFP-GDP) has been used as a photolabile analogue of (E, E)-farnesyl diphosphate (E, E-FDP) for an aid in isolating enzymes utilizing E, E-FDP as a substrate. We now report an alternative method of synthesizing this probe in which the tritium label is introduced in the step just before the introduction of the diphosphate group. Thus, DATFP-geraniol is oxidized to DATFP-geranial with activated manganese dioxide. The tritium label is introduced by reduction of the aldehyde with NaBT4. The DATFP-group successfully withstands both of these steps. The overall yield for these two steps is 69%. Diphosphorylation of the resulting alcohol afforded DATFP-[1-3H]-GDP in 8% yield with a specific activity of 48.6 μCi/μmol and radiochemical purity of 94%.