Synthesis of the fluorine-18 labeled inhalation anesthetics.
Fourteen compounds (fluoroalkanes and fluoroethers), including the two most utilized inhalation anesthetics Isoflurane (CF3CHClOCF2H) and Halothane (CF3CHBrCl), have been labeled with fluorine-18 via a facile 18F-for-19F exchange reaction. The compounds include ten inhalation anesthetics which span a ten-fold range in potency and four structurally related non-anesthetics. All the compounds possess a trifluoromethyl group (CF3) adjoining a carbon atom with an acidic alpha-hydrogen and at least one halogen or a strong electron withdrawing group (X), [CF3CHXR]. We postulate the isotopic fluoride exchange reaction proceeds through a carbanion transition state resulting from alpha-proton transfer to base. The carbanion stability is attributed to the inductive effect of the CF3 group and the electron withdrawing capability of X. Compounds labeled in dimethyl sulfoxide (DMSO) at 125 degrees C in 15 min include Isoflurane-CF3CHClOCF2H (1) (97% [18F]fluorine incorporation, 99% radiochemical purity, respectively), Sevoflurane-CF3CHCF3OCFH2 (2) [98%, 99%], CF3CHBrOCF2H (3) [85%, 80%], Desflurane-CF3CHFOCF2H (4) [50%, 99%], Fluroxene-CF3CH2OCH = CH2 (5) [25%, 99%], Fluothyl-CF3CH2OCH2CF3 (6) [60%, 10% at a temperature of 175 degrees C], Halothane-CF3CHBrCl (7) [98%, 95%], CF3CH2I (8) [99%, 98%], CF3CH2Br (9) [18%, 98%], CF3CHCl2 (10) [95%, 98%], CF3CH2Cl (11) [90%, 20%], CF3CHClCF3 (12) [95%, 99%], (CF3)3CH (13) [99%, 99%] and HF-134a-CF3CFH2 (14) (15%, 93% at a temperature of 175 degrees C).
Satter
M R
MR
Department of Nuclear Medicine/PET, Kettering Memorial Hospital, Dayton, OH 45429.
Martin
C C
CC
Oakes
T R
TR
Christian
B F
BF
Nickles
R J
RJ
D018685:Anesthetics, Inhalation / Q000138:chemical synthesis*; D002849:Chromatography, Gas; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*
D018685:Anesthetics, Inhalation; D005462:Fluorine Radioisotopes