Synthesis and characterization of the aqueous solution chemistry of the food-derived carcinogen model N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide and its N-pivaloyloxy analogue

Rajagopal, Sridharan; Brooks, Michael E.; Nguyen, Thach‐Mien; Novák, Michael

doi:10.1016/j.tet.2003.08.005

Cited by 11 publications

(23 citation statements)

References 26 publications

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“…The reaction of 3-acetyl-2-cyanomethylindole with ammonia leads to 3-amino-1-methyl-γ-carboline, which can also be obtained by the acylation of 2-cyanomethylindole with acetonitrile in the presence of AlCl 3 [38]. During the reaction with acetonitrile in a mixture of acetic acid and methanol the yield of the γ-carboline derivative can be increased to 40% [39]. The dienaminocarbonyl structural fragment is a convenient five-carbon component for the construction of the pyridine ring by reaction with ammonia or primary amines.…”

Section: Methods Of Synthesis Of γ-Carbolinesmentioning

confidence: 99%

γ-Carbolines and their hydrogenated derivatives. 1. Aromatic γ-carbolines: methods of synthesis, chemical and biological properties (review)

Alekseyev

Kurkin

Yurovskaya

2009

Chem Heterocycl Comp

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Section: Methods Of Synthesis Of γ-Carbolinesmentioning

confidence: 99%

γ-Carbolines and their hydrogenated derivatives. 1. Aromatic γ-carbolines: methods of synthesis, chemical and biological properties (review)

Alekseyev

Kurkin

Yurovskaya

2009

Chem Heterocycl Comp

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“…and mutagenic heterocyclic arylamines (Scheme 4.29). [147][148][149][150][151][152] McClelland and Licence used the azides 102m,n as photoprecursors of heteroaryl nitrenium ions. 153 The chemistry of these species has been recently reviewed.…”

Section: Heterocyclic Nitrenium Ionsmentioning

confidence: 99%

“…Product studies showed that the k H and k A terms involve ester hydrolysis to form the corresponding hydroxamic acids or hydroxylamines. [149][150][151][152] …”

Section: Heterocyclic Nitrenium Ionsmentioning

confidence: 99%

“…Products consistent with generation of a nitrenium ion are detected under these conditions, although ester hydrolysis to form the hydroxamic acid is also part of the k B rate term for less reactive substrates. 150,151,154 The rate law is more complicated than that for reactive esters of carbocyclic hydroxylamines or hydroxamic acids that show pH-independent decomposition over a wide pH range. 18,19,27 The carbocyclic esters do not have basic sites that can be protonated under mild pH conditions.…”

Section: Heterocyclic Nitrenium Ionsmentioning

confidence: 99%

“…154 The ions 103a-l were characterized by their reactions with N 3 À , 2 0 -deoxyguanosine (dG) and the aqueous solvent. [147][148][149][150][151][152] The log (k az /k s ) ratios derived from azide clock studies or by direct measurement are provided in Table 4.2 with some comparisons to carbocyclic ions. The more selective ions 103d-g exhibit reactivity with HPO 4 2À and H 2 PO 4 À .…”

Section: Heterocyclic Nitrenium Ionsmentioning

confidence: 99%

See 2 more Smart Citations

Aryl Nitrenium Ions in Aqueous Solution

Novák

Wang

2013

Nitrenes and Nitrenium Ions

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N‐Arylhydroxylamines and Chemical Carcinogenicity

Novák¹,

Chakraborty²

2010

Patai's Chemistry of Functional Groups

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Two related classes of carcinogens, arylamines (AAs) and heterocyclic arylamines (HAAs), have played an important role in the development of our understanding of chemical carcinogenesis. AAs are largely industrial products or by‐products, but significant exposure also occurs through inhalation of cigarette smoke. HAAs are produced during broiling or frying of meats and fish and are viewed as significant cancer risks in most human populations. AAs and HAAs are properly characterized as procarcinogens because they require metabolic activation into their ultimate carcinogenic forms. Both classes are activated predominately by cytochrome P450 (CYP450) mediated oxidation into N ‐arylhydroxylamines that are further metabolized into acetic or sulfuric acid esters of the hydroxylamines by the action of N ‐acetyltransferases (NATs) or sulfotransferases (SULTs). These esters appear to be the ultimate carcinogens in most cases. Research on the metabolism of AAs and HAAs, the structures of DNA adducts derived from their carcinogenic metabolites, and the relationship of DNA adduct conformations and persistence to observed mutations are reviewed. Evidence for the proposal that the reactive intermediate responsible for the formation of DNA adducts is a nitrenium ion derived from the hydroxylamine esters is the main topic of this review. Future prospects for research in this area are considered. Introduction Metabolic Activation of AAs and HAAs The Structures of DNA Adducts The Nitrenium Ion Hypothesis The Hypothesis Tested Concluding Remarks

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Synthesis and characterization of the aqueous solution chemistry of the food-derived carcinogen model N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide and its N-pivaloyloxy analogue

Cited by 11 publications

References 26 publications

γ-Carbolines and their hydrogenated derivatives. 1. Aromatic γ-carbolines: methods of synthesis, chemical and biological properties (review)

γ-Carbolines and their hydrogenated derivatives. 1. Aromatic γ-carbolines: methods of synthesis, chemical and biological properties (review)

Aryl Nitrenium Ions in Aqueous Solution

N‐Arylhydroxylamines and Chemical Carcinogenicity

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