Enzymology of Oxime Formation

Oxime formation can occur by various mechanisms. One possibility is the direct oxygenation of imino groups. The stoichiometry of this process is given in equation 4, where R2 = H (or alkyl) to yield either aldoximes or ketoximes. 

Closer inspection of oxime formation from the stable 2,4,6-trimethylacetophenone imine revealed the N-oxygenating activity to be sensitive to the presence of proto-typic inhibitors of the P-450 system, such as carbon monoxide, SKF 525A and DPEA1. 

Introduction of R2 = NH2 into the structure of the parent imine presented in equation 4 yields an amidine, which can be subject to N-oxygenation. Thus, a series of benza-midines have been detected to undergo conversion to benzamidoximes (24a), and this process appears to be catalyzed by P-450, as evidenced by susceptibility of the microsomal turnover to CO or SKF 525A and the inability of highly purified hog liver FMO 

FIGURE 1. Correlation between log Umax and the Hammett ap constant for NADPH-sustained N-oxygenation of a series of fia/a substituted benzamidines by rabbit liver supernatant fraction. (Data taken from Ref. 47, with permission) 

It has to be pointed out that imines do not only serve as substrates for the N-oxygenase(s) when added exogenously to assay mixtures, but are also acted upon by these enzymes when metabolically formed from primary amines. Thus, it is interesting to note that benzylmethyl ketimine has been proposed as an intermediate in microsomal 

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