Stereochemistry nitrosamine

Gold and Linder (17) studied the esterase catalyzed hydrolysis of A-(-)-acetoxymethyl-(l-phenylethyl)nitrosamine. They found that the stereochemistry of 1-phenylethanol produced in the reaction was the same as that observed in the base catalyzed hydrolysis of the nitrosamine and also of N-(l-phenylethyl)nitrosocarbamate. These results indicated that the same diazotate was produced in all three reactions. The fact that no irreversible inhibition of the enzymatic hydrolysis of the nitrosamine was observed, while extensive irreversible inhibition was obtained with the nitrosocarba-mate, led these workers to conclude that the a-hydroxynitro-samine produced by the hydrolysis had sufficient stability to diffuse away from the active site of the enzyme. 

The importance of the stereochemistry of the nitrosamine function in the mutagenicity and carcinogenicity of these compounds has not been demonstrated and yet there is considerable indirect evidence that such a stereochemical dependence may be important. It is evident that the metabolism can be related to a stereochemical factor for unsyrametrical nitrosamines. These, of course, give either of two oxygenated metabolites, and there is evidence that only one of these is mutagenic in some cases (23, 24). Thus, the metabolism may be at least regiospecific, if not stereospecific, relative to the nitrosamine function. 

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