Alkyl nitrosamines

Ross and Chiarello (1979) have described a method for denitrosation of nitrosamines, such as dlalkylnitrosamines e.g. N-nitrosodimetl laminer etc., and complex aryl-alkyl nitrosamines, e.g. N-nitroso-N-(l-ethylpropyl)-3,4-dimethyl-2,6-dinitroaniline. The products of nitration and amination containing nitrosamlne as a substantial impurity are treated with an aldehyde or ketone in the presence of strong acids such as hydrochloric or hydrobromic acid. Under pressurized conditions at 105-110% for cme to two hours, the nitrosamlne is destroyed. The desired product can be recovered after neutralization of the excess acid. The equation shows the denitrosation of pendimethalin ... 

It had been suggested a number of years ago that methyl alkyl nitrosamines are hydroxylated enzymatically on the methyl group to give a-hydroxymethylnitrosamines (2, 3). 

Similar types of mutation are caused by mutagens which alkylate bases, such as the alkyl nitrosamines, which alkylate the N7 and O6 of guanine (figure 6,31). This may lead to a G C—>A T transition. 

Symmetrical dialkyl-nitrosamines Methyl alkyl nitrosamines Cyclic nitrosamines Aryl-alkyl and diaryl nitrosamines... 

Whatever the true details of the metabolic pathway shown in Scheme 1 might be, there are certain facts which are very secure. Among these are that the nitrosamines are oxidatively dealkylated, that electrophilic intermediates which alkylate proteins and nucleic acids are formed, and that one of the... 

Although the o-hydroxylation hypothesis has been given considerable support, it is clear that nitrosamines with alkyl side chains longer than methyl present additional possibilities for biological activation. It was stated earlier that even the o-hydroxylation hypothesis is based on considerable circumstantial evidence. This means that the other possible pathways are even more speculative, and hence, much more research needs to be carried out before some of the ideas advanced below will gain acceptance, or be put to rest. 

Nitrosamines require metabolic activation in order to produce a chemical species that will alkylate nucleophilic sites on a biomolecule such as DNA (1, . The crucial initial step in the... 

Metabolism of nitrosamines from tobacco generates a series of electrophiles that alkylate DNA, and some of the resulting adducts can also regenerate electrophilic intermediates illustrated in Scheme 9.4. This oxonium ion can be terminally quenched... 

R, R1 = alkyl, aryl, COR, CONHR Fig. 3.2 N-N restricted rotation in N-nitrosamines. 

The a-carbons of nitrosamines undergo enzymatic hydroxylation followed by oxidative cleavage leading to the formation of alkyldiazo hydroxides, alkyldiazonium ions and alkyl cations [34]. These cations are postulated to initiate the process of carcinogenesis in some cases by alkylating the base units of DNA [35, 36]. 

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