Summary
Studies of the in vivo metabolism of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one (2) specifically deuteriated at C-7 implicate an arene oxide intermediate during the conversion to 7-hydroxy-2 (4) as evidenced by the observation of the NIH shift.
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Incubation of1 with the cytosol fraction prepared from rat liver homogenate gave good conversions (>70%) into the lactam2. In an attempt to distinguish between the alternative insertion and addition pathways, i.e. between enol lactam and oxaziridine intermediates for this transformation, a kinetic isotope approach was adopted. Using a 1∶1 mixture of1-11-d 91 and non-deuteriated1 (H/D=1), the H/D ratio was derermined in unchanged1 throughout the course of the incubation (0–45 min). The H/D ratio did not deviate significantly from unity with time. In the absence of a full kinetic analysis of the system and a certain knowledge of the rate-determining step, no conclusions can be drawn from this result. A similar view has been suggested recently13 and must cast doubt on the validity of a meaningful interpretation based on the absence of a primary kinetic isotope effect14.
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Harrison, J.M., Clarke, R.J., Inch, T.D. et al. The metabolism of dibenz[b,f]-1,4-oxazepine (CR): In vivo hydroxylation of 10,11-dihydrodibenz[b,f]-1,4-oxazepin-11-(1OH)-one and the NIH shift. Experientia 34, 698–699 (1978). https://doi.org/10.1007/BF01947265
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DOI: https://doi.org/10.1007/BF01947265