SYNTHESIS OF C-11 C-13-LABELED PROSTACYCLINS

A one-pot synthesis of 1]methylphenyl)-17,18,19,20-tetranorisocarbacyc lin methyl ester was performed using a palladium-promoted reaction of [C-11]methyl iodide with ( stannylphenyl)-17,18,19,20,-tetranorisocarb acyclin methyl ester. The C-15 epimer(l5S)-16-( 3-[C-11] methylphenyl) 17,18,19,20-tetranorisocarbacyclin methyl ester was synthesised in the same way starting from ylstannylphenyl)17,18,19,20-tetranorisocarbacy clin methyl ester. The decay-corrected radiochemical yields were 33-45 % based on [C-11]methyl iodide produced, and the radiochemical purify of the product was > 95%. The total synthesis time was 35 min, counted from end of radionuclide production to product ready for administrati on. The C-11-labelled prostacyclin methyl esters were easily hydrolyse d using sodium hydroxide affording the C-11-labelled prostacyclin acid s in quantitative yields. The stereoisomers 3-methylphenyl)-17,18,19,2 0-tetranorisocarbacyclin [C-11]methyl ester and 3-methylphenyl)-17,18, 19,20-tetranorisocarbacyclin [C-11]methyl ester were synthesised by es terification using [C-11]methyl iodide and the tetrabutylammonium salt s of 3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid and (15S) -16-(3-methylphenyl)-17, 18,19,20-tetranorisocarbacyclin acid, respect ively. The decay-corrected radiochemical yields were in the range of 5 5% counting from [C-11]methyl iodide produced, and the radiochemical p urity of the product was > 95%. The total synthesis time was 35 min, c ounting from end of radionuclide production to product ready for admin istration. Both of these labelling methods can be used for labelling w ith C-13 when (C-13)methyl iodide is used. The methods described herei n have already proved important since they enable the in vivo use of P ET to study the action of prostacyclins in the brain.