SYNTHESIS OF THE F-18 LABELED INHALATION ANESTHETICS

Fourteen compounds (fluoroalkanes and fluoroethers), including the two most utilized inhalation anesthetics Isoflurane (CF3CHClOCF2H) and Ha lothane (CF3CHBrCl), have been labeled with fluorine-18 via a facile F -18-for-F-19 exchange reaction. The compounds include ten inhalation a nesthetics which span a ten-fold range in potency and four structurall y 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), {CF( 3)CHXR}. We postulate the isotopic fluoride exchange reaction proceeds through a carbanion transition state resulting from alpha-proton tran sfer to base. The carbanion stability is attributed to the inductive e ffect of the CF3 group and the electron withdrawing capability of X. C ompounds labeled in dimethyl sulfoxide (DMSO) at 125 degrees C in 15 m in include Isoflurane-CF3CHClOCF2H (1) (97% [F-18]fluorine incorporati on, 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-CF3CH2 OCH2CF3 (6) [60%, 10% at a temperature of 175 degrees C], Halothane-CF 3CHBrCl (7) [98%, 95%], CF3CH2I (8) [99%, 98%], CF3CH2Br (9) [18%, 98% ], CF3CH2Cl (10) [95%, 98%], CF3CHCl2 (11) [90%, 20%], CF3CHClCF3 (12) [95%, 99%], (CF3)(3)CH (13) [99%, 99%] and HF-134a-CF3CFH2 (14) (15%, 93% at a temperature of 175 degrees C).