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Organic & Biomolecular Chemistry Mar 2021Aldehyde deformylation is an important reaction in biology, organic chemistry and inorganic chemistry and the process has been widely applied and utilized. For instance,... (Review)
Review
Aldehyde deformylation is an important reaction in biology, organic chemistry and inorganic chemistry and the process has been widely applied and utilized. For instance, in biology, the aldehyde deformylation reaction has wide differences in biological function, whereby cyanobacteria convert aldehydes into alkanes or alkenes, which are used as natural products for, e.g., defense mechanisms. By contrast, the cytochromes P450 catalyse the biosynthesis of hormones, such as estrogen, through an aldehyde deformylation reaction step. In organic chemistry, the aldehyde deformylation reaction is a common process for replacing functional groups on a molecule, and as such, many different synthetic methods and procedures have been reported that involve an aldehyde deformylation step. In bioinorganic chemistry, a variety of metal(iii)-peroxo complexes have been synthesized as biomimetic models and shown to react efficiently with aldehydes through deformylation reactions. This review paper provides an overview of the various aldehyde deformylation reactions in organic chemistry, biology and biomimetic model systems, and shows a broad range of different chemical reaction mechanisms for this process. Although a nucleophilic attack at the carbonyl centre is the consensus reaction mechanism, several examples of an alternative electrophilic reaction mechanism starting with hydrogen atom abstraction have been reported as well. There is still much to learn and to discover on aldehyde deformylation reactions, as deciphered in this review paper.
Topics: Aldehydes; Biomimetic Materials; Coordination Complexes; Cytochrome P-450 Enzyme System; Models, Chemical; Oxidation-Reduction
PubMed: 33406196
DOI: 10.1039/d0ob02204g -
Applied and Environmental Microbiology Mar 2015Aldehydes are a class of chemicals with many industrial uses. Several aldehydes are responsible for flavors and fragrances present in plants, but aldehydes are not known... (Review)
Review
Aldehydes are a class of chemicals with many industrial uses. Several aldehydes are responsible for flavors and fragrances present in plants, but aldehydes are not known to accumulate in most natural microorganisms. In many cases, microbial production of aldehydes presents an attractive alternative to extraction from plants or chemical synthesis. During the past 2 decades, a variety of aldehyde biosynthetic enzymes have undergone detailed characterization. Although metabolic pathways that result in alcohol synthesis via aldehyde intermediates were long known, only recent investigations in model microbes such as Escherichia coli have succeeded in minimizing the rapid endogenous conversion of aldehydes into their corresponding alcohols. Such efforts have provided a foundation for microbial aldehyde synthesis and broader utilization of aldehydes as intermediates for other synthetically challenging biochemical classes. However, aldehyde toxicity imposes a practical limit on achievable aldehyde titers and remains an issue of academic and commercial interest. In this minireview, we summarize published efforts of microbial engineering for aldehyde synthesis, with an emphasis on de novo synthesis, engineered aldehyde accumulation in E. coli, and the challenge of aldehyde toxicity.
Topics: Aldehydes; Escherichia coli; Metabolic Engineering; Microbial Viability
PubMed: 25576610
DOI: 10.1128/AEM.03319-14 -
Molecules (Basel, Switzerland) Mar 2019The recent developments in asymmetric A³ (aldehyde⁻alkyne⁻amine) coupling has been summarized in this review. Several interesting modifications of the ligands... (Review)
Review
The recent developments in asymmetric A³ (aldehyde⁻alkyne⁻amine) coupling has been summarized in this review. Several interesting modifications of the ligands enabled the highly enantioselective synthesis of chiral propargylamines, which are further used in the construction of nitrogen-containing chiral building blocks.
Topics: Aldehydes; Alkynes; Amines; Catalysis; Pargyline; Propylamines; Stereoisomerism
PubMed: 30925732
DOI: 10.3390/molecules24071216 -
Drug Metabolism Reviews Feb 2019Aldehydes are carbonyl compounds found ubiquitously in the environment, derived from both natural and anthropogenic sources. As the aldehydes are reactive species,... (Review)
Review
Aldehydes are carbonyl compounds found ubiquitously in the environment, derived from both natural and anthropogenic sources. As the aldehydes are reactive species, therefore, they are generally toxic to the body. To reduce the toxicity and pathogenesis related to aldehydes, the human body contains several aldehyde metabolizing enzyme systems including aldehyde oxidases, cytochrome P450 enzymes, aldo-ketoreductases, alcohol dehydrogenases, short-chain dehydrogenases/reductases and aldehyde dehydrogenases (ALDHs). These enzyme systems maintain a low level of aldehydes in the body by catalytically converting them into less-harmful and easily excreted products. The human ALDH (hALDH) superfamily consists of 20 functional ALDH genes identified so far at distinct chromosomal locations, expressing 20 ALDH proteins, which belong to 11 different ALDH families. They are involved in the NAD(P)-dependent oxidation of a wide range of exogenous and endogenous aldehydes to their corresponding carboxylic acids. The hALDHs are present in all sub-cellular locations and have a wide tissue distribution. This review gives an account of aldehydes; their source, toxicity and metabolism, different aldehyde metabolizing enzymes with special emphasis on ALDHs including their biochemical, physiological and pathophysiological roles in the body.
Topics: Aldehyde Dehydrogenase; Aldehydes; Animals; Carcinogenesis; Drug Resistance; Humans; Inactivation, Metabolic
PubMed: 30514131
DOI: 10.1080/03602532.2018.1555587 -
Nutrition Reviews Nov 1963
Review
Topics: Aldehydes; Humans; Retinaldehyde
PubMed: 14084318
DOI: 10.1111/j.1753-4887.1963.tb04701.x -
Cardiovascular Research Oct 2010Numerous conditions promote oxidative stress, leading to the build-up of reactive aldehydes that cause cell damage and contribute to cardiac diseases. Aldehyde... (Review)
Review
Numerous conditions promote oxidative stress, leading to the build-up of reactive aldehydes that cause cell damage and contribute to cardiac diseases. Aldehyde dehydrogenases (ALDHs) are important enzymes that eliminate toxic aldehydes by catalysing their oxidation to non-reactive acids. The review will discuss evidence indicating a role for a specific ALDH enzyme, the mitochondrial ALDH2, in combating oxidative stress by reducing the cellular 'aldehydic load'. Epidemiological studies in humans carrying an inactive ALDH2, genetic models in mice with altered ALDH2 levels, and small molecule activators of ALDH2 all highlight the role of ALDH2 in cardioprotection and suggest a promising new direction in cardiovascular research and the development of new treatments for cardiovascular diseases.
Topics: Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Aldehydes; Animals; Enzyme Activation; Heart Diseases; Humans; Isoenzymes; Mitochondria, Heart; Myocardium; Oxidation-Reduction; Oxidative Stress
PubMed: 20558439
DOI: 10.1093/cvr/cvq192 -
Current Medicinal Chemistry 2019In recent years, aldehyde-appended fluorescence probes have attracted increasing attention. Fluorescent biological imaging includes many modern applications for cell and... (Review)
Review
In recent years, aldehyde-appended fluorescence probes have attracted increasing attention. Fluorescent biological imaging includes many modern applications for cell and tissue imaging in biomedical research. Meanwhile, the nucleophilic mechanism is a very simple and convenient procedure for the preparation of aldehyde-sensing probes. This tutorial review focuses on aldehyde-bearing chemosensors based on nucleophilic addition mechanism with biological applications.
Topics: Aldehydes; Biomedical Research; Fluorescent Dyes; Humans; Molecular Imaging; Optical Imaging; Spectrometry, Fluorescence
PubMed: 29345575
DOI: 10.2174/0929867325666180117095528 -
Expert Opinion on Therapeutic Patents Oct 2023Physiological and pathophysiological effects arising from detoxification of aldehydes in humans implicate the enzyme aldehyde dehydrogenase (ALDH) gene family comprising... (Review)
Review
INTRODUCTION
Physiological and pathophysiological effects arising from detoxification of aldehydes in humans implicate the enzyme aldehyde dehydrogenase (ALDH) gene family comprising of 19 isoforms. The main function of this enzyme family is to metabolize reactive aldehydes to carboxylic acids. Dysregulation of ALDH activity has been associated with various diseases. Extensive research has since gone into studying ALHD isozymes, their structural biology and developing small-molecule inhibitors. Novel chemical strategies to enhance the selectivity of ALDH inhibitors have now appeared.
AREAS COVERED
A comprehensive review of patent literature related to aldehyde dehydrogenase inhibitors in the last decade and half (2007-2022) is provided.
EXPERT OPINION
Aldehyde dehydrogenase (ALDH) is an important enzyme that metabolizes reactive exogenous and endogenous aldehydes in the body through NAD(P)±dependent oxidation. Hence this family of enzymes possess important physiological as well as toxicological roles in human body. Significant efforts in the field have led to potent inhibitors with approved clinical agents for alcohol use disorder therapy. Further clinical translation of novel compounds targeting ALDH inhibition will validate the promised therapeutic potential in treating many human diseases.The scientific/patent literature has been searched on SciFinder-n, Reaxys, PubMed, Espacenet and Google Patents. The search terms used were 'ALDH inhibitors', 'Aldehyde Dehydrogenase Inhibitors'.
Topics: Humans; Patents as Topic; Aldehyde Dehydrogenase; Aldehydes; Enzyme Inhibitors; Isoenzymes
PubMed: 38037334
DOI: 10.1080/13543776.2023.2287515 -
Chemical Research in Toxicology Jul 2014Aldehydes are electrophilic compounds to which humans are pervasively exposed. Despite a significant health risk due to exposure, the mechanisms of aldehyde toxicity are... (Review)
Review
Aldehydes are electrophilic compounds to which humans are pervasively exposed. Despite a significant health risk due to exposure, the mechanisms of aldehyde toxicity are poorly understood. This ambiguity is likely due to the structural diversity of aldehyde derivatives and corresponding differences in chemical reactions and biological targets. To gain mechanistic insight, we have used parameters based on the hard and soft, acids and bases (HSAB) theory to profile the different aldehyde subclasses with respect to electronic character (softness, hardness), electrophilic reactivity (electrophilic index), and biological nucleophilic targets. Our analyses indicate that short chain aldehydes and longer chain saturated alkanals are hard electrophiles that cause toxicity by forming adducts with hard biological nucleophiles, e.g., primary nitrogen groups on lysine residues. In contrast, α,β-unsaturated carbonyl derivatives, alkenals, and the α-oxoaldehydes are soft electrophiles that preferentially react with soft nucleophilic thiolate groups on cysteine residues. The aldehydes can therefore be grouped into subclasses according to common electronic characteristics (softness/hardness) and molecular mechanisms of toxicity. As we will discuss, the toxic potencies of these subgroups are generally related to corresponding electrophilicities. For some aldehydes, however, predictions of toxicity based on electrophilicity are less accurate due to inherent physicochemical variables that limit target accessibility, e.g., steric hindrance and solubility. The unsaturated aldehydes are also members of the conjugated type-2 alkene chemical class that includes α,β-unsaturated amide, ketone, and ester derivatives. Type-2 alkenes are electrophiles of varying softness and electrophilicity that share a common mechanism of toxicity. Therefore, exposure to an environmental mixture of unsaturated carbonyl derivatives could cause "type-2 alkene toxicity" through additive interactions. Finally, we propose that environmentally derived aldehydes can accelerate diseases by interacting with endogenous aldehydes generated during oxidative stress. This review provides a basis for understanding aldehyde mechanisms and environmental toxicity through the context of electronic structure, electrophilicity, and nucleophile target selectivity.
Topics: Aldehydes; Animals; Humans
PubMed: 24911545
DOI: 10.1021/tx5001046 -
Bioconjugate Chemistry May 2013Since the 1990s, α-oxo aldehyde or glyoxylic acid chemistry has inspired a vast array of synthetic tools for tailoring peptide or protein structures, for developing... (Review)
Review
Since the 1990s, α-oxo aldehyde or glyoxylic acid chemistry has inspired a vast array of synthetic tools for tailoring peptide or protein structures, for developing peptides endowed with novel physicochemical properties or biological functions, for assembling a large diversity of bioconjugates or hybrid materials, or for designing peptide-based micro or nanosystems. This past decade, important developments have enriched the α-oxo aldehyde synthetic tool box in peptide bioconjugation chemistry and explored novel applications. The aim of this review is to give a large overview of this creative field.
Topics: Aldehydes; Amino Acid Sequence; Chemistry Techniques, Synthetic; Glyoxylates; Models, Molecular; Molecular Sequence Data; Peptides
PubMed: 23578008
DOI: 10.1021/bc300516f