1. 14C-Paxilline incubated in bile from pasture-fed sheep was efficiently transformed to a more polar dioxygenated derivative in which the
indole 2,3 double-bond had opened to give an 8-membered ring. The structure is proposed on the basis of mass spectrometry and 1H- and 13C-n.m.r. spectroscopy. The new compound is 2,18-dioxo-2,18-seco-paxilline. 2. The
paxilline transformation also occurred in bile which had been boiled to inactive
enzymes. 3. The dissolved
oxygen concentration in freshly collected sheep bile was in the range 38-163 nmol/ml. 4. Whereas
paxilline causes pronounced
tremor in the mouse given 4 mg/kg i.p., the dioxygenated
paxilline was biologically inactive at ten times this dose. 5. The feasibility that analogous oxidative transformation of
indole-
diterpenoid tremorgenic
mycotoxins may occur, increasing polarity advantageously to
xenobiotic elimination, during biliary elimination from agricultural ruminants in the field, is recognized. Concomitant loss of tremorgenicity is an additional benefit. 6. The biotransformation of
paxilline in sheep bile was mimicked by ozonolysis but the
ozone equivalent 4-t-butyl-iodoxybenzene was not similarly effective.