A new approach for the synthesis of [11C]-labeled fatty acids

Article abstract of DOI:10.1002/1099-1344(200011)43:13<1289::AID-JLCR420>3.0.CO;2-Q

The synthesis of ω-[¹¹C], ω-1-[¹¹C] and ω-3-[¹¹C] palmitic acid employing a cross-coupling reaction between a functionalized copper-zinc reagent with [¹¹C]MeI, [1-¹¹C]EtI and [1-¹¹C]BuI is described. A tert.-butyl-protected ω-iodo fatty acid precursor (t)BuO₂C-(CH₂)(n)-I (n = 11, 13, 14) was converted into the corresponding dialkylzinc reagent [(t)BuO₂C-(CH₂)(n)]₂Zn which reacts with Me₂CuI(MgCl)₂ to give a highly reactive copper reagent [(t)BuO₂C-(CH₂)(n)]₂CuI(MgCl)₂Me₂Zn as the labeling precursor. The cross-coupling reaction with [¹¹C]MeI, [1-¹¹C]EtI and [1-¹¹C]BuI provided the protected palmitic acid, specifically labeled with carbon-11 in several positions. The corresponding carbon-13 labeled compounds were synthesized to verify the labeling position. In a typical synthesis with [1-¹¹C]EtI starting with 250 mCi of [¹¹C]CO₂, 14 mCi (6% decay-corrected based on [¹¹C]CO₂) of ω-1-[¹¹C]palmitic acid was obtained within 30 minutes after EOB in 88% radiochemical purity prior to purification by HPLC. The general feature of this approach allows the convenient synthesis of palmitic acid specifically labeled in the ω, ω-1 or ω-3 positions by using several [¹¹C]-labeled alkyl iodides ([¹¹C]MeI, [1-¹¹C]EtI or [1-¹¹C]BuI) in the same cross-coupling protocol.