Fluorine labeled isomer

For compounds that contain a limited number of fluorine atoms, heteronuclear correlation spectroscopy experiments such as F H HETCOR and 2H-19F heteronuclear Overhauser enhancement spectroscopy (HOESY) can provide considerable assistance distinguishing structural isomers and diastereomers as well as for conformational analysis. HOESY experiments have been frequently used for conformational analysis of biomolecules containing fluorine labels.18... 

H. Luo, A.L. Beets, M.J. McAllister, M. Greenbaum, D.W. McPherson, F.F. Knapp Jr, Resolution, in vitro and in vivo evaluation of fluorine-18-labeled isomers of 1-azabi-cyclo[2.2.2]oct-3-yl a -(1-fluoropent-5-yl)- a -hydroxy- a -phenylacetate (FQNPe) as new PET candidates for the imaging of muscarinic-cholinergic receptor, J. Label. Compd. Radiopharm. 41 (1998) 681-704. 

For nonquantitative -C-NMR techniques, this could be the extent of the analysis possible. However, the combination of F-NMR with C-NMR allowed us to quantitatively calculate the isomer composition and to investigate solvent effects on isomer formation. Figure 17.5 illustrates these concepts. Two possible isomers (structures in Figure 17.5) can be formed from the reaction of 3-fluorophthalic anhydride with 4-fluoroaniline. Upon formation of the amic acid based on 3-fluorophthalic anhydride with 4-fluoroaniline, two isomers were found in both NMP and chloroform reactions as shown by the F-NMR spectra in Figure 17.5a and b, respectively. Two signals were observed for each type of fluorine atom, labeled as Fi and F2 for the anhydride and amine fluorine atoms respectively. Ortho and meta isomers were formed in a ratio of 4.75 1 in solution in NMP, while the same ratio was 1.04 1 in chloroform, where the product precipitated. The major isomer was the ortho in each case as determined by C-NMR of the chloroform prepared amic acid (Table 17.1). 

Time-consuming work-up procedures must be avoided in the synthesis of labeled diagnostics, but essentially the usual fluorination methods are used. [1 F]FDG can be prepared by electrophilic fluorination of a glycal with [ F acctyl hypofluorite [87] (Scheme 4.40). This reagent again is produced by reaction of F labeled fluorine gas with KOAc -2HOAc [88]. The synthesis of other [ F]fluor-odopa isomers is illustrated in Scheme 4.41. 

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