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Journal of Food Protection Nov 2021This review provides an assessment of heterocyclic amine (HCA) formation and mitigation in processed meat and meat products. HCAs are formed when amino acids react with... (Review)
Review
ABSTRACT
This review provides an assessment of heterocyclic amine (HCA) formation and mitigation in processed meat and meat products. HCAs are formed when amino acids react with creatine during thermal processing of meat and meat products. The formation of HCAs depends on various factors, including the temperature, cooking time, fat contents, and presence of HCA precursors such as water, lipids, and marinades. Additional factors that could affect HCA formation are pH, meat type, and ingredients added during cooking such as antioxidants, amino acids, ions, fat, and sugars, which promote production of HCAs. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline, 2-amino-3-methylimidazo-[4,5-f]quinoline, and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline are HCAs of importance because of their link to cancer in humans. More than 25 HCAs have been identified in processed foods. Of these, nine HCAs are possible human carcinogens (group 2B) and one is a probable human carcinogen (group 2A). To mitigate HCA generation during heat processing, various techniques have been used, including recipe variations, adjustments of thermal processing conditions, addition of flavorings, pretreatments such as microwave heating, and addition of naturally occurring and artificial antioxidants.
Topics: Amines; Cooking; Heterocyclic Compounds; Humans; Meat; Meat Products
PubMed: 33956955
DOI: 10.4315/JFP-20-471 -
Molecules (Basel, Switzerland) Jun 2022In this review, we focus on some interesting and recent examples of various applications of organic azides such as their intermolecular or intramolecular, under thermal,... (Review)
Review
In this review, we focus on some interesting and recent examples of various applications of organic azides such as their intermolecular or intramolecular, under thermal, catalyzed, or noncatalyzed reaction conditions. The aforementioned reactions in the aim to prepare basic five-, six-, organometallic heterocyclic-membered systems and/or their fused analogs. This review article also provides a report on the developed methods describing the synthesis of various heterocycles from organic azides, especially those reported in recent papers (till 2020). At the outset, this review groups the synthetic methods of organic azides into different categories. Secondly, the review deals with the functionality of the azido group in chemical reactions. This is followed by a major section on the following: (1) the synthetic tools of various heterocycles from the corresponding organic azides by one-pot domino reaction; (2) the utility of the chosen catalysts in the chemoselectivity favoring C-H and C-N bonds; (3) one-pot procedures (i.e., Ugi four-component reaction); (4) nucleophilic addition, such as Aza-Michael addition; (5) cycloaddition reactions, such as [3+2] cycloaddition; (6) mixed addition/cyclization/oxygen; and (7) insertion reaction of C-H amination. The review also includes the synthetic procedures of fused heterocycles, such as quinazoline derivatives and organometal heterocycles (i.e., phosphorus-, boron- and aluminum-containing heterocycles). Due to many references that have dealt with the reactions of azides in heterocyclic synthesis (currently more than 32,000), we selected according to generality and timeliness. This is considered a recent review that focuses on selected interesting examples of various heterocycles from the mechanistic aspects of organic azides.
Topics: Amination; Azides; Catalysis; Cyclization; Cycloaddition Reaction
PubMed: 35744839
DOI: 10.3390/molecules27123716 -
Molecules (Basel, Switzerland) Feb 2023The Ugi four-component reaction (Ugi-4CR) undoubtedly is the most prominent multicomponent reaction (MCRs) that has sparked organic chemists' interest in the field. It... (Review)
Review
The Ugi four-component reaction (Ugi-4CR) undoubtedly is the most prominent multicomponent reaction (MCRs) that has sparked organic chemists' interest in the field. It has been widely used in the synthesis of diverse heterocycle molecules such as potential drugs, natural product analogs, pseudo peptides, macrocycles, and functional materials. The Ugi-4CRs involve the use of an amine, an aldehyde or ketone, an isocyanide, and a carboxylic acid to produce an α-acetamido carboxamide derivative, which has significantly advanced the field of isocyanide-based MCRs. The so-called intermediate nitrilium ion could be trapped by a nucleophile such as azide, -hydroxyphthalimide, thiol, saccharin, phenol, water, and hydrogen sulfide instead of the original carboxylic acid to allow for a wide variety of Ugi-type reactions to occur.β In addition to isocyanide, there are alternative reagents for the other three components: amine, isocyanide, and aldehyde or ketone. All these alternative components render the Ugi reaction an aptly diversity-oriented synthesis of a myriad of biologically active molecules and complex scaffolds. Consequently, this review will delve deeper into alternative components used in the Ugi MCRs, particularly over the past ten years.
Topics: Peptides; Amines; Cyanides; Carboxylic Acids; Aldehydes
PubMed: 36838630
DOI: 10.3390/molecules28041642 -
Molecules (Basel, Switzerland) Apr 2023The development of heterocyclic derivatives has progressed considerably over the past decades, and many new carbonic anhydrase inhibitors (CAIs) fall into this field. In... (Review)
Review
The development of heterocyclic derivatives has progressed considerably over the past decades, and many new carbonic anhydrase inhibitors (CAIs) fall into this field. In particular, five-membered heterocyclic sulfonamides have been generally shown to be more effective inhibitors compared to six-membered rings ones. Despite the importance of oxygen and nitrogen five-membered heterocyclic aromatic rings in medicinal chemistry, the installation of sulfonamide moiety on such heterocycles has not received much attention. On the other hand, 1,3,4-thiadiazole/thiadiazoline ring-bearing sulfonamides are the scaffolds which have been widely used in a variety of pharmaceutically important CAIs such as acetazolamide, metazolamide and their many derivatives obtained by using the tail approach. Here, we reviewed the field focusing on the diverse biological activities of these CAIs, such as antiglaucoma, antiepileptic, antitumor and antiinfective properties. This review highlights developments involving five-membered heterocyclic sulfonamides over the last years, with a focus on their pharmacological/clinical applications.
Topics: Carbonic Anhydrase Inhibitors; Sulfonamides; Structure-Activity Relationship; Acetazolamide; Anticonvulsants; Sulfanilamide; Dermatologic Agents
PubMed: 37049983
DOI: 10.3390/molecules28073220 -
Molecules (Basel, Switzerland) Dec 2022Sulfonamides are the basic motifs for a whole generation of drugs from a large group of antibiotics. Currently, research in the field of the new sulfonamide synthesis... (Review)
Review
Sulfonamides are the basic motifs for a whole generation of drugs from a large group of antibiotics. Currently, research in the field of the new sulfonamide synthesis has received a "second wind", due to the increase in the synthetic capabilities of organic chemistry and the study of their medical and biological properties of a wide spectrum of biological activity. New reagents and new reactions make it possible to significantly increase the number of compounds with a sulfonamide fragment in combination with other important pharmacophore groups, such as, for example, a wide class of -containing heterocycles. The result of these synthetic possibilities is the extension of the activity spectrum-along with antibacterial activity, many of them exhibit other types of biological activity. Antiviral activity is also observed in a wide range of sulfonamide derivatives. This review provides examples of the synthesis of sulfonamide compounds with antiviral properties that can be used to develop drugs against coxsackievirus B, enteroviruses, encephalomyocarditis viruses, adenoviruses, human parainfluenza viruses, Ebola virus, Marburg virus, SARS-CoV-2, HIV and others. Since over the past three years, viral infections have become a special problem for public health throughout the world, the development of new broad-spectrum antiviral drugs is an extremely important task for synthetic organic and medicinal chemistry. Sulfonamides can be both sources of nitrogen for building a nitrogen-containing heterocyclic core and the side chain substituents of a biologically active substance. The formation of the sulfonamide group is often achieved by the reaction of the -nucleophilic center in the substrate molecule with the corresponding sulfonylchloride. Another approach involves the use of sulfonamides as the reagents for building a nitrogen-containing framework.
Topics: Humans; Antiviral Agents; Sulfonamides; COVID-19; SARS-CoV-2; Sulfanilamide; Anti-Bacterial Agents; Indicators and Reagents; Nitrogen
PubMed: 36615245
DOI: 10.3390/molecules28010051 -
Angewandte Chemie (International Ed. in... May 2020The development of efficient and selective C-N bond-forming reactions from abundant feedstock chemicals remains a central theme in organic chemistry owing to the key...
The development of efficient and selective C-N bond-forming reactions from abundant feedstock chemicals remains a central theme in organic chemistry owing to the key roles of amines in synthesis, drug discovery, and materials science. Herein, we present a dual catalytic system for the N-alkylation of diverse aromatic carbocyclic and heterocyclic amines directly with carboxylic acids, by-passing their preactivation as redox-active esters. The reaction, which is enabled by visible-light-driven, acridine-catalyzed decarboxylation, provides access to N-alkylated secondary and tertiary anilines and N-heterocycles. Additional examples, including double alkylation, the installation of metabolically robust deuterated methyl groups, and tandem ring formation, further demonstrate the potential of the direct decarboxylative alkylation (DDA) reaction.
Topics: Acridines; Alkylation; Amines; Aniline Compounds; Catalysis; Heterocyclic Compounds; Oxidation-Reduction
PubMed: 32050048
DOI: 10.1002/anie.201916710 -
Nutrition and Cancer 2009High intake of meat, particularly red and processed meat, has been associated with an increased risk of a number of common cancers such as breast, colorectum, and... (Review)
Review
High intake of meat, particularly red and processed meat, has been associated with an increased risk of a number of common cancers such as breast, colorectum, and prostate in many epidemiological studies. Heterocyclic amines (HCAs) are a group of mutagenic compounds found in cooked meats, particularly well-done meats. HCAs are some of most potent mutagens detected using the Ames/salmonella tests and have been clearly shown to induce tumors in experimental animal models. Over the past 10 years, an increasing number of epidemiological studies have evaluated the association of well-done meat intake and meat carcinogen exposure with cancer risk. The results from these epidemiologic studies were evaluated and summarized in this review. The majority of these studies have shown that high intake of well-done meat and high exposure to meat carcinogens, particularly HCAs, may increase the risk of human cancer.
Topics: Amines; Animals; Breast Neoplasms; Colorectal Neoplasms; Cooking; Diet; Female; Heterocyclic Compounds; Hot Temperature; Humans; Male; Meat; Meat Products; Mutagens; Neoplasms; Pancreatic Neoplasms; Prostatic Neoplasms
PubMed: 19838915
DOI: 10.1080/01635580802710741 -
International Journal of Molecular... Oct 20226-Hydroxyquinoline and 3-hydroxyisoquinoline as -containing naphthol analogues were tested in modified Mannich reactions (Mr's). In the case of 6-hydroxyquinoline, the...
6-Hydroxyquinoline and 3-hydroxyisoquinoline as -containing naphthol analogues were tested in modified Mannich reactions (Mr's). In the case of 6-hydroxyquinoline, the outcomes of the attempted Mannich reactions were strongly influenced by the amine components. Aminoalkylation of this substrate with reagents 1-naphthaldehyde and -benzylmethylamine led to the isolation of a diol regarded as a stabilised water adduct of an -quinone methide (-QM), of which formation can be ascribed to the presence of a hydroxide ion in a relatively higher concentration generated by the bulky and basic amine component with decreased nucleophilicity. The classical Mannich base was isolated as a single product when the amine component was replaced for morpholine, featuring nucleophilicity rather than basic character under the applied reaction conditions. Starting from the isomer substrate 3-hydroxyisoquinoline, independently on the nucleophile (methanol or morpholine) besides the formation of the classical Mannich base, the nucleophilic attack at position one of the heterocyclic substrate was also observed. The DFT analysis of the acceptor molecular orbitals of the potential electrophilic components and the thermodynamics of the assumed-possible transformations demonstrated that this regioselective addition is a feasible process on the investigated heterocyclic skeleton. DFT modelling studies also suggest that besides the steric bulk, the orbital-controlled electronic properties of the aryl group, originating from the aldehyde components, have a strong influence on the ratios and the NMR-monitored interconversions of the C-1-substituted 3-hydroxyisoquinolines and the classical Mannich bases formed in multistep reaction sequences. On the basis of the DFT analysis of the thermodynamics of alternative pathways, a reaction mechanism was proposed for the rationalization of these characteristic substrate-controlled interconversions.
Topics: Mannich Bases; Naphthols; Methanol; Water; Morpholines; Aldehydes
PubMed: 36293186
DOI: 10.3390/ijms232012329 -
Chemical Research in Toxicology Jan 2022Heterocyclic aromatic amines (HAAs) are mainly formed in the pyrolysis process during high-temperature cooking of meat. Meat consumption is very typical of the western... (Review)
Review
Heterocyclic aromatic amines (HAAs) are mainly formed in the pyrolysis process during high-temperature cooking of meat. Meat consumption is very typical of the western diet, and the amount of meat consumption in the eastern countries is growing rapidly; HAAs represents widespread exposure. HAAs are classified as possible human carcinogens; numerous epidemiological studies have demonstrated regular consumption of meat with HAAs as risk factor for cancers. Specific HAAs have received major attention. For example, 2-amino-1-methyl-6-phenylimidazo[4,5-] pyridine has been extensively studied as a genotoxicant and mutagen, with emergent literature on neurotoxicity. Harmane has been extensively studied for a role in essential tremors and potentially Parkinson's disease (PD). Harmane levels have been demonstrated to be elevated in blood and brain in essential tremor patients. Meat consumption has been implicated in the etiology of neurodegenerative diseases; however, the role of toxicants formed during meat preparation has not been studied. Epidemiological studies are currently examining the association between HAAs and risk of neurodegenerative diseases such as essential tremors and PD. Studies from our laboratory and others have provided strong evidence that HAA exposure produces PD and Alzheimer's disease-relevant neurotoxicity in cellular and animal models. In this review, we summarize and critically evaluate previous studies on HAA-induced neurotoxicity and the molecular basis of potential neurotoxic effects of HAAs. The available studies provide strong support for the premise that HAAs may impact neurological function and that addressing gaps in understanding of adverse neurological outcomes is critical to determine whether these compounds are modifiable risk factors.
Topics: Amines; Animals; Heterocyclic Compounds; Humans; Neurodegenerative Diseases
PubMed: 34990108
DOI: 10.1021/acs.chemrestox.1c00274 -
Chemical Reviews Oct 2016Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds... (Review)
Review
Pd-catalyzed cross-coupling reactions that form C-N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C-N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.
Topics: Amidines; Aniline Compounds; Biological Products; Carbamates; Catalysis; Cyclization; Heterocyclic Compounds; Hydrazines; Hydrazones; Ligands; Palladium; Sulfonamides; Urea
PubMed: 27689804
DOI: 10.1021/acs.chemrev.6b00512