Co(salen)-mediated enantioselective radiofluorination of epoxides. Radiosynthesis of enantiomerically enriched [18F]F-MISO via kinetic resolution

Asymmetric18F-fluorination for applications in positron emission tomography

“…In 2013, Revunov and Zhuravlev took inspiration from the cobalt mediated enantioselective epoxide opening reaction. 25 This work employed [ 18 F]fluoride treated with H 2 SO 4 , proposed by the authors to form [ 18 F]HF, which could be trapped by addition of (–)-tetramisole. The reaction took place by addition of ( R , R )-Co(salen), HFIP and an epoxide precursor in either MTBE or 2-methyl-2-butanol ( t AmOH) as solvent ( Scheme 3C ).…”

Automated synthesis and PET evaluation of both enantiomers of [18F]FMISO

“…The GC was performed on a Shimadzu GC-2010 equipped with FactorFour calillary column, VF-200 ms, 30 m, 0.32 mm. The aqueous solutions of [ 18 F]fluoride were prepared by the 18O(p,n) 18 F reaction in a GE PETtrace cyclotron by irradiating 95% enriched [18O]water (2 mL) with the nominal 16.5 MeV beam at 55 μA for 60-90 min. The decay corrected preparative radiochemical yields (RCYs) of both enantiomers of [ 18 F]F-MISO were determined on the cartridge-purified sterile saline formulation of the product relative to [ 18 F]fluoride.…”

“…Our approach to radiosynthesis of enantiopure (R)-and (S)-[ 18 F]FMISO was based on a recently disclosed transition metal mediated enantioselective epoxide opening which utilized [ 18 F]HF in a combination with (-)tetramisole and (R,R)-Co(salen) [18]. To maximize the enantiomeric purity of the desired (R)-and (S)-[ 18 F]FMISO the radiosynthesis was performed on enantiopure substrates.…”

Ring opening of epoxides with [18F]FeF species to produce [18F]fluorohydrin PET imaging agents

“…3 Despite these features, [ 18 F]HF has seldom been utilized for the synthesis of PET imaging agents. [4][5][6][7][8][9][10] This is surprising because it is a historically important reagent for fluorinating organic molecules and was used to prepare the first two fluorine-containing drugs, fludrocortisone and dexamethasone. [11][12][13] In particular, the production of fluorohydrin, a motif found in a variety of known radiotracers, via epoxide opening has remained a challenge in radiochemistry.…”

“…This is complementary to recent (salen)CoF methods developed separately by both Zhuravlev and Doyle which were regioselective for the less-substituted fluoride, typically on terminal epoxides (Figure 1c). 10,14 Previous work from our group has shown that [ 18 F]Ftrapped on a quaternary methylammonium (QMA) cartridge can be eluted using a solution of an organic base (e.g. DMAP, DBU) to provide a reactive and soluble source of [ 18 F]Fwithout the need for an inorganic base (K 2 CO 3 ) or K 2.2.2 .…”