Palladium-promoted synthesis of compounds labelled with ¹¹C : Synthesis of ¹¹C-labelled prostacyclin and prostaglandin analogues

Abstract: Palladium-promoted reactions have been employed for the synthesis of compounds labelled with 11C (t½ = 20.3 min). The precursor [11C]methyl iodide was used in palladium-promoted cross-coupling reactions with organostannanes. With this method, large molecules with several functional groups, that is prostacyclin analogues, have been synthesised in up to 54 % decay-corrected radiochemical yield, calculated from [11C]methyl iodide. However, since this method did not afford reproducible yields, a second method where copper(I) was used as a co-catalyst with palladium, was developed. In the second method, a lower reaction temperature could be used and more reproducible yields were obtained. Employing this method, a prostaglandin analogue was synthesised in 34 % decay-corrected radiochemical yield calculated from [11C]methyl iodide. The total synthesis time was 30 min and the radiochemical purity was higher than 95 %. The specific radioactivity of the compounds obtained with these two methods was approximately 100 GBq/μmol.11C-Labelled aliphatic and aromatic alkenes were synthesised from [11C]methyl iodide in a Wittig olefination reaction using a published method. The 11C-labelled alkenes were reacted with five aromatic halidein Heck coupling reactions, producing five [11C]stilbene analogues in 34-40 % decay-corrected radiochemical yield. The radiochemical purity was higher than 95 % and the total synthesis timwas 40 min. 11C-Labelled alkenes were also synthesised from 11C-labelled aldehydes. The 11C-labelled aldehydes were obtained from [11C]carbon monoxide in a palladium-mediated formylation of aryl iodides in 51-87 % radiochemical yield, determined by analytical LC and corrected for trappinefficiency. A range of palladium catalysts and hydride reagents were investigated. The labelled aldehydes were used in a subsequent Wittig olefination reaction where various Wittig salts were employed tsynthesise a variety of alkenes. The radiochemical yields were 30-76 %, determined by analytical LC.