Nitrosamide alkyl

There is much evidence to suggest that carcinogenic N-nitros-amines are metabolised by an oxidative process to produce an alkylating agent (J f2) One potential metabolite is therefore the corresponding N-nitrosamide resulting from 2-electron oxidation at the oc-carbon atom, and, indeed, such compounds appear to induce tumours at the site of application without metabolic activation (3) It follows that the chemical properties of N-nitrosamides are relevant to the etiology of cancer ... 

One goal of our current investigation is to show that genetically important cellular constituents can initiate the release of an alkylating agent from the N-nitrosamide. This might explain how highly reactive diazohydroxide metabolites effect the alkylation of nucleic acids within the cell nucleus. Preliminary evidence ( ) summarised in Table II shows that the decomposition of... 

A reagent composed of tetra-n-butylammonium nitrate and TFAA in methylene chloride has been used to nitrate a series of A-alkyl and A-aryl amides (40-90 %). The formation of significant amounts of A-nitrosamides was noted. Tetra-n-butylammonium nitrate and triflic anhydride in methylene chloride has been used to successfully nitrate a variety of heterocyclic amides, imides and ureas (66). ... 

Zimmermann, F.K., Schwaier, R. von Laer, U. (1966) Mitotic recombination induced in Saccharomyces cerevisiae with nitrous acid, diethyl sulfate and carcinogenic, alkylating nitrosamides. Z. Vererbungsl., 98, 230-246... 

Broadly, NOC are divided into two groups (a) /V-nitrosamines and (b) N-nitrosamides. In jV-nitrosamines, the two remaining substituent groups on the >N—N=0 atom can be either alkyl or aryl, or they can form the part of a heterocyclic ring (as in N-nitrosopyrrolidine). On the other hand, in N-nitrosamides, more correctly called N-acyl-N-nitroso compounds, one of these... 

Saturated /V-haloamides and /V-nitrosamides, upon UV photolysis, undergo remote functionalizations 8 to nitrogen on the alkyl or, less effec-... 

Rearrangement of N-nitrosoamides. N-Nitrosamides (1), prepared by acetylation of primary amines followed by nitrosation, are known to decompose in nonpolar solvents at 80-100° to form alkyl acetates with elimination of nitrogen.9 The presumed diazoalkane intermediate (a) can be trapped as a rhodium carbene (b), which undergoes rearrangement to an alkene (equation I). The overall result is a mild, nonbasic version of the classical Hofmann degradation of amines. 

Unlike polycyclic aromatic hydrocarbons, nitrosamines require only the first activation step which forms a hydroxylated intermediate that is sufficiently unstable to spontaneously decompose and generate a reactive carbonium which can rapidly alkylate target macromolecules in the cell. In contrast, nitrosamides do not require metabolic activation because of inherent chemical instability in aqueous solution. Nitrosamides decompose at physiological pH nonenzymatically to produce the same class of reactive electrophiles as the nitrosamines. Although the actual target site for nitroso carcinogens is not yet elucidated, a number of alkylation sites in DNA are known such as 0 -CH3-G, 7-CH3-G, and 3-CH3-A (2). 

The most salient commonality among the 210 carcinogens that are positive in Salmonella is the electrophilicity that is intrinsic to the molecule or introduced by enzymatic modification. The former can be thought of as ultimate mutagens and include known or presumable alkylating and acylating agents diazo compounds, nitrosamides, nitrosoureas, dimethylcarbamyl chloride, diaryl alkynyl carbamates, aziridines, oxiranes, thiirane,... 

The nitrosamines and nitrosamides, for example, are highly carcinogenic derivatives, and in vivo they are metabolized to diazoalkane or alkyl carbonium ions, both of which will react with DNA (Fig. 13). The highly carcinogenic aromatic... 

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