title: Synthesis of 11C/13C-labelled prostacyclins.
abstract: A one-pot synthesis of (15R)-16-(3-[11C]methylphenyl)-17,18,19, 20-tetranoriso-carbacyclin methyl ester was performed using a palladium-promoted reaction of [11C]methyl iodide with (15R)-16-(3-tri-n-butylstannylphenyl)-17,18,19, 20-tetranorisocarbacyclin methyl ester. The C-15 epimer (15S)-16-(3-[11C]methylphenyl)-17,18,19,20-tetranorisocarbacyclin methyl ester was synthesised in the same way starting from (15S)-16-(3-tributylstannylphenyl)-17,18,19,20-tetranorisocarba cyclin methyl ester. The decay-corrected radiochemical yields were 33-45% based on [11C]methyl iodide produced, and the radiochemical purity of the product was > 95%. The total synthesis time was 35 min, counted from end of radionuclide production to product ready for administration. The 11C-labelled prostacyclin methyl esters were easily hydrolysed using sodium hydroxide affording the 11C-labelled prostacyclin acids in quantitative yields. The stereoisomers (15R)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin [11C]methyl ester and (15S)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin [11C]methyl ester were synthesised by esterification using [11C]methyl iodide and the tetrabutylammonium salts of (15R)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid and (15S)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid, respectively. The decay-corrected radiochemical yields were in the range of 55% counting from [11C]methyl iodide produced, and the radiochemical purity of the product was > 95%. The total synthesis time was 35 min, counting from end of radionuclide production to product ready for administration. Both of these labelling methods can be used for labelling with 13C when (13C)methyl iodide is used. The methods described herein have already proved important since they enable the in vivo use of PET to study the action of prostacyclins in the brain.
authors.affiliation: Department of Organic Chemistry, Uppsala University, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Björkman
authors.forename: Y
authors.initials: Y
authors.lastname: Andersson
authors.forename: H
authors.initials: H
authors.lastname: Doi
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: R
authors.initials: R
authors.lastname: Noyori
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D002247:Carbon Isotopes; D002853:Chromatography, Liquid; D011464:Epoprostenol / Q000138:chemical synthesis* / Q000302:isolation & purification; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002247:Carbon Isotopes; D011464:Epoprostenol