Facile N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the flavin-containing monooxygenase. A convenient synthesis of tritiated [methyl-3H]-4-phenyl-2,3-dihydropyridinium species.
A rapid, efficient procedure useful for the radiosynthesis of [Me-3H]-MPDP+ ([methyl-3H]-4-phenyl-2,3-dihydropyridinium species) is described. Hog liver microsomes or the highly purified flavin-containing monooxygenase from hog liver quantitatively biotransforms [Me-3H]-MPTP to its corresponding radiolabeled N-oxide. For the small-scale synthesis required for radiolabeling procedures, this enzymatic process is superior to H2O2-mediated N-oxygenation of MPTP. In the presence of 0.5 mM NADPH, 4.5 mM n-octylamine, and 2 microCi [Me-3H]-MPTP, the only product detected in extracts from incubations performed with hog liver microsomes or purified hog liver flavin-containing monooxygenase is [Me-3H]-MPTP N-oxide. [Me-3H]-MPTP N-oxide is almost completely converted to [Me-3H]-MPDP+ by the action of trifluoroacetic anhydride. This procedure has the advantage of using a commercially available tritiated starting material, efficient transformations, and easily accomplished purification to afford a rapid synthesis of [Me-3H]-MPDP+.
Cashman
J R
JR
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D008862:Microsomes, Liver / Q000201:enzymology; D010105:Oxygenases / Q000494:pharmacology*; D011725:Pyridines / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism*; D013552:Swine; D014316:Tritium
D011725:Pyridines; D011726:Pyridinium Compounds; D014316:Tritium; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)