Alkylation

About: Alkylation is a research topic. Over the lifetime, 29915 publications have been published within this topic receiving 464944 citations. The topic is also known as: alkylation reaction.

Possible Relevance of O–6 Alkylation of Deoxyguanosine to the Mutagenicity and Carcinogenicity of Nitrosamines and Nitrosamides

Abstract: BIOLOGICAL alkylating agents—“mustards”, ethylenimines, epoxides and alkyl alkanesulphonates—have been believed to induce mutations by causing atypical base pairing during DNA replication at sites bearing a guanine residue which has suffered alkylation at the 7(N) position1,2. The most abundant reaction product found in acid hydrolysates of treated DNA is 7-alkyl guanine3,4, although alkylated adenines and cytosine, notably 3-alkyl adenine, are recovered as minor products. Furthermore, genetic studies of alkylation mutants in bacteria and bacteriophages have shown that many point mutational events involve guanine to adenine transitions5,6.

Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents.

Abstract: Alkylating agents, because of their ability to react directly with DNA either in vitro or in vivo, or following metabolic activation as in the case of the dialkylnitrosamines, have been used extensively in studying the mechanisms of mutagenicity and carcinogenicity. Their occurrence is widespread in the environment and human exposure from natural and pollutant sources is universal. Since most of these chemicals show varying degrees of both carcinogenicity and mutagenicity, and exhibit compound-specific binding patterns, they provide an excellent model for studying molecular dosimetry. Molecular dosimetry defines dose as the number of adducts bound per macromolecule and relates the binding of these adducts to the human mutagenic or carcinogenic response. This review complies DNA alkylation data for both methylating and ethylating agents in a variety of systems and discusses the role these alkylation products plays in molecular mutagenesis.

Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation

Abstract: Nitrogen heterocycles are present in many compounds of enormous practical importance, ranging from pharmaceutical agents and biological probes to electroactive materials. Direct functionalization of nitrogen heterocycles through C−H bond activation constitutes a powerful means of regioselectively introducing a variety of substituents with diverse functional groups onto the heterocycle scaffold. Working together, our two groups have developed a family of Rh-catalyzed heterocycle alkylation and arylation reactions that are notable for their high level of functional-group compatibility. This Account describes our work in this area, emphasizing the relevant mechanistic insights that enabled synthetic advances and distinguished the resulting transformations from other methods. We initially discovered an intramolecular Rh-catalyzed C-2 alkylation of azoles by alkenyl groups. That reaction provided access to a number of di-, tri-, and tetracyclic azole derivatives. We then developed conditions that exploited mic...