Synthesis of a Biochemically Important Aldehyde, 3,4-Dihydroxyphenylacetaldehyde

Li, Shu Wen; Spaziano, Vincent T.; Burke, William J.

doi:10.1006/bioo.1998.1087

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…Tissue levels of CA and metabolites reported here are consistent with earlier reports (19,23,29,30). We describe for the first time a detailed method for quantitation of DOPAL and DOPEGAL, two recently synthesized CA metabolites (8,9), from 12 related CA and metabolites. In our assay protein was removed from tissues by PCA precipitation.…”

Section: Discussionsupporting

confidence: 91%

“…DOPAL and DOPEGAL were prepared as we have described (8,9). All other chemicals were purchased from either Aldrich (Milwaukee, WI) or Sigma (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

“…A major problem in measuring levels of DOPAL and DOPEGAL has been lack of a standard. We have recently described procedures for chemical synthesis and purification of DOPAL (8) and DOPEGAL (9). This synthesis allows for the first time accurate quantitation of DOPAL and DOPEGAL.…”

Section: 4-dihydroxyphenylacetaldehyde (Dopal)mentioning

confidence: 99%

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Quantitation of 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde, the Monoamine Oxidase Metabolites of Dopamine and Noradrenaline, in Human Tissues by Microcolumn High-Performance Liquid Chromatography

Burke

Chung

1999

Analytical Biochemistry

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Section: Discussionsupporting

confidence: 91%

“…DOPAL and DOPEGAL were prepared as we have described (8,9). All other chemicals were purchased from either Aldrich (Milwaukee, WI) or Sigma (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

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Quantitation of 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde, the Monoamine Oxidase Metabolites of Dopamine and Noradrenaline, in Human Tissues by Microcolumn High-Performance Liquid Chromatography

Burke

Chung

1999

Analytical Biochemistry

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“…1 H NMR spectra were collected in both CDCl 3 and DMSO-d 6 for direct comparison with conflicting reports from the literature (25,26). Our results are in good agreement with Tsukamoto et al (26).…”

Section: Methodsmentioning

confidence: 99%

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Anderson

Mariappan

Buettner

et al. 2011

Journal of Biological Chemistry

122

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The oxidation and toxicity of dopamine is believed to contribute to the selective neurodegeneration associated with Parkinson disease. The formation of reactive radicals and quinones greatly contributes to dopaminergic toxicity through a variety of mechanisms. The physiological metabolism of dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL) via monoamine oxidase significantly increases its toxicity. To more adequately explain this enhanced toxicity, we hypothesized that DOPAL is capable of forming radical and quinone species upon oxidation. Here, two unique oxidation products of DOPAL are identified. Several different oxidation methods gave rise to a transient DOPAL semiquinone radical, which was characterized by electron paramagnetic resonance spectroscopy. NMR identified the second oxidation product of DOPAL as the ortho-quinone. Also, carbonyl hydration of DOPAL in aqueous media was evident via NMR. Interestingly, the DOPAL quinone exists exclusively in the hydrated form. Furthermore, the enzymatic and chemical oxidation of DOPAL greatly enhance protein cross-linking, whereas auto-oxidation results in the production of superoxide. Also, DOPAL was shown to be susceptible to oxidation by cyclooxygenase-2 (COX-2). The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition. Parkinson disease (PD)2 involves specific loss of dopaminergic nuclei in the substantia nigra of the brain (1). Although the exact causes of this selective degeneration are unknown (2), the role of affected cells as centers of dopamine (DA) synthesis, storage, and metabolism suggests that DA may be an endogenous neurotoxin (3, 4) that contributes to the pathogenesis of PD. DA may act as a source of cellular oxidative stress and is known to undergo oxidation (Scheme 1) to cytotoxic radicals and quinones (5-8). Such oxidations can occur spontaneously or via metal-or enzyme-catalyzed mechanisms (9). One-electron oxidation of DA produces a radical capable of interfering with DA storage and causing oxidative protein and DNA modifications (5, 6, 10). Similarly, two-electron oxidation of DA to an ortho-quinone results in reactivity with cellular nucleophiles such as thiols and proteins (8, 11). Both species are capable of redox cycling, which could deplete cellular oxidative defenses. Also, in the presence of transition metals and/or O 2 , such oxidations could result in the production of ROS capable of inducing lipid peroxidation and damage to other cellular macromolecules (12). Another potential mechanism of toxicity for DA is its physiological metabolism to 3,4-dihydroxyphenylacetaldehyde (DOPAL) (13).DOPAL is a very reactive aldehyde that is 100 -1000-fold more toxic than DA both in vivo and in vitro (14,15). Physiological levels of DOPAL in the substantia nigra are ϳ2 M; levels as low as 6 M can exert significant toxicity (16). Reactivity with proteins, presumably via Schiff base formation, is an important mechanism o...

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“…Li et al. first described the synthesis and characterization of 3,4‐dihydroxyphenylacetaldehyde (DOPAL; a metabolic intermediate deriving from dopamine), which required the use of restricted starting materials (e.g., piperonal, which is on the list of controlled substances under drug legislation) and environmentally unfriendly conditions (strong acids or bases; toxic solvents; and reagents, such as benzene, POCl 3 , and mercury salts), to yield the desired products in low‐to‐moderate amounts (14–60 %) –. More recently, the groups of Reimann and Carosi reported on the preparation of (3,4‐dimethoxyphenyl)‐ and (3‐methoxyphenyl)acetaldehyde, respectively.…”

Section: Methodsmentioning

confidence: 99%

Transaminase‐Catalyzed Continuous Synthesis of Biogenic Aldehydes

Contente

Paradisi

2019

ChemBioChem

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The physiological role of biogenic aldehydes, such as 3,4-dihydroxyphenylacetaldehyde (DOPAL), has been associated with cardiovascular and neurodegeneratived isorders. The availability of these substrates is limited and robust synthetic methodologies would greatly facilitate further biological studies. Herein, at ransaminase-mediated single-step process in continuous mode, which leads to excellent product yields (90-95 %), is reported. Coimmobilization of the pyridoxal phosphate (PLP) cofactor eliminated the need for exogenous addition of this reagent without affecting the longevity of the system,d elivering at ruly self-sufficient process.Aldehydes species are continuouslyg enerated in biological systemsf rom aw ide range of endo-and exogenous precursors. [1a] Biogenic aldehydes are defined as those formed endogenously through enzyme-dependento rs pontaneouso xidation of lipids, sugars,a nd primary amines. [1b-e] Thankst ot he strong electrophilicity of the terminal carbonyl group, they are considered to be the most reactive compounds between biomolecules. [2] If not metabolized, biogenic aldehydesc an become cytotoxic due to covalent modificationso ra dduct formation with proteins( typically Cys, Lys, His, and Arg residues), [3] nucleic acids( involving amino groups of both purines and pyrimidines), [4] and coenzymes, [5] with subsequent inactivation through Michael addition, Knoevenagel condensation, Schiff base, and free radical formation.M oreover,a ldehydes are relatively long-lived, so they not only reactw ith targets in their proximity,b ut can also diffuse or be transported to remote sites. [6] Although, originally,b iogenic aldehydes were believed to be innocuous intermediates predominantly formed by oxidative amination with monoamine oxidase (MAO), recent studies demonstrated that not only weret hey neurotransmitters themselves, [7] but they were also involved in the development of cardiovascular [8] and neurodegenerative diseases (such as Alzheimer's and Parkinson's diseases) [7] and played ak ey role in alcohol-related disorders. [2] Synthetically,n umerous attempts have been reportedf or the preparation of biogenic aldehydes. [9a-d] However,t hese methodologies requires everal steps, drastic reaction condi- [a] Dr.

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Synthesis of a Biochemically Important Aldehyde, 3,4-Dihydroxyphenylacetaldehyde

Cited by 16 publications

References 26 publications

Quantitation of 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde, the Monoamine Oxidase Metabolites of Dopamine and Noradrenaline, in Human Tissues by Microcolumn High-Performance Liquid Chromatography

Quantitation of 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde, the Monoamine Oxidase Metabolites of Dopamine and Noradrenaline, in Human Tissues by Microcolumn High-Performance Liquid Chromatography

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Transaminase‐Catalyzed Continuous Synthesis of Biogenic Aldehydes

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