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In this paper two hypotheses are tested:  (i) the active oxygen species is similar in energetics for all cytochrome P450 (CYP) enzymes and (ii) linear free-energy relationships can be used to evaluate the mechanism of the reaction of these enzymes. A series of intramolecular isotope effects were determined and compared for CYPs 1A2, 2B1, 2C9, 2E1, and P450cam. The results indicate that the isotope effects are very similar for each of these isoforms of P450 and that the first hypothesis is likely to be true. Attempts to establish a linear free-energy relationship were only moderately successful:  log V max = 0.11σ+ p + 1.73; r 2 = 0.588. It was determined, through the use of intermolecular isotope effects, that the rates of hydrogen atom abstraction are masked. Thus, the second hypothesis is found to be false. This is likely to be a general result for CYP reactions, and linear free-energy relationships can only be used to determine the mechanism under very special circumstances. In all cases, the rate-limiting step should be evaluated with isotope effect experiments before any mechanistic conclusions can be drawn. If the intermolecular isotope effects are found to be masked, no mechanistic conclusion can be drawn from the linear free-energy relationship study.

Utilizing the spiro[adamantane‐Δ4‐isoxazoline] precursor 10, a key 2‐acylaziridine intermediate (11) has been isolated, thus providing conclusive evidence that an initial ring contraction may be considered to be the first step of the Δ4‐isoxazoline‐pyrrole rearrangement.

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The synthesis of a number of new 2-adamantanone oxime carbamate derivatives (7a-h) is described. When tested in the carrageenin-induced rat paw edema assay, some of the compounds exerted moderate anti-inflammatory activity. In addition, the title 2-adamantanone oxime carbamates showed in vitro antifungal activity against yeast and systemic mycoses and dermatophytes. Synthese uad biologisehe AktivitZt von 2-Adamantanonoxim-CarbamatenEs wird die Synthese von einigen neuer Carbamaten des Adamantanon-2 Oxims beschrieben. Bei der Prufung des durch Carrageenin ausgelosten Pfotenodem-Modell der Ratte zeigten einige Derivate mafiige entzundungshemmende Wirkungen. AuJ3erdem wirkten die im Titel genannten Adamantanon-2-oxim-Carbamate pilzhemmend in vitro gegen Hefen, systematische Mykosen und Dermatophyten.Over the years, a number of oxime ether derivatives of acetophenone'-E), (iso)phthalaldehydic I), benzophenonei2, and benzyl methyl ketone'4) have been prepared and studied for biological activity. Most notably, anti-inflammatory1 9,12-14), as well as immunosuppresdve9~ lo), a n a l g e s i~~-~.~-~, !*-I4), antipyreticg), anticonvulsant6, l4) and thymolytici4) activities were found to be associated with the presence of an oxime ether group. Furthermore, a series of phenylcyanomethylene q~inone oxime ether derivatives 1 were synthesized by Seidl and Nesemannl5) and reported to possess antiallergic, analgesic, fungicidal and parasiticidal activities.As reported by van Dijk and Zwagemakerss) a number of new 2-hydroxyethyl and carboxyalkyl ethers of aromatic oximes displayed a potent anti-inflammatory activity in the carrageenin-induced rat paw edema assay. One of their compounds, cloximate 12) was selected to undergo clinical evaluation as anti-inflammatory agent. However, relatively very little has been reported on the synthesis and biological activity of 2-adamantanone oxime analogs. Thus, the O-(2-dimethylaminoethyl)-2-adamantanone oxime (CM 54903) (3) has shown psychotropic activityi6). 1 2 NOCR tI NOCH*CHzN( CH3) 2 3 4 0 0365-6233/87/0505-465 $02.50/0 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1987Georgiev and coworkers Arch. Pharm.