Total Synthesis and Detection of the Bilirubin Oxidation Product (Z)-2-(3-Ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide (Z-BOX A)

Klopfleisch, Maurice; Seidel, Raphael A.; Görls, Helmar; Richter, Hannes; Beckert, Rainer; Imhof, Wolfgang; Reiher, Markus; Pohnert, Georg; Westerhausen, Matthias

doi:10.1021/ol402221b

Cited by 21 publications

(57 citation statements)

References 18 publications

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“…As expected from the structure of heme the Z-configuration of the exocyclic double bond could be confirmed by UPLC-co-injection experiments with a synthetic reference [14]. Rough estimations of BOXes concentrations in CSF were obtained with high performance liquid chromatography coupled to ultra violet spectroscopy (HPLC-UV).…”

Section: Introductionmentioning

confidence: 60%

“…In accordance with earlier studies this reaction can be explained as the photochemical Z/E-isomerization of the exocyclic double bond between the heterocycle and the acetamide moiety (see structures in Scheme 1). [14] These compounds generated during light exposure could be detected at the same SRM transition (m/z 179 → 162) as used for the analytes Z-BOX A and Z-BOX B and show similar fragmentation patterns. Hence the peaks at 4.52 and 4.80 min were tentatively assigned to E-BOX A and E-BOX B (Fig.…”

Section: Stabilitymentioning

confidence: 84%

“…The two regio-isomers Z-BOX A and Z-BOX B were purified from the crude bilirubin oxidation mixture according to Klopfleisch et al [14]: The dried chloroform extract of the crude bilirubin oxidation mixture was suspended in acetonitrile/water (20/80 v/v) and centrifuged at 16,100 × g. The supernatant was purified on a Shimadzu LC-8A HPLC system (Kyoto, Japan) equipped with a SPD-10AV UV-VIS detector measuring at 310 nm. Isocratic separation was achieved on a HTEC C18 column (250 mm × 16 mm, 5 m; Macherey-Nagel, Düren, Germany) equilibrated with acetonitrile/water (20/80 v/v) at a flow rate of 6 mL/min.…”

Section: Purification Of Analytesmentioning

confidence: 99%

“…Due to formation of strong hydrogen bonds the analytes Z-BOX A and Z-BOX B are hardly soluble in water [14]. We utilized this feature to achieve a strong interaction of the analytes with the stationary phase by using a C-18 reversed phase column [9].…”

Section: Liquid Chromatography and Matrix Effectmentioning

confidence: 99%

“…The loss of ammonia (m/z 179 → 162) was the dominant fragmentation in both analyte isomers and already took place under mild conditions. Collision energies above 19 eV led to a strong decrease of the m/z 162 fragment in favor of the fragment with m/z 134 that is formed due to further neutral loss of carbon monoxide [14]. For the detection of 5-bromonicotinamide the formation of Br + (m/z 201 → 79) was monitored.…”

Section: Optimization Of Mass Spectrometrymentioning

confidence: 99%

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Simultaneous determination of the bilirubin oxidation end products Z-BOX A and Z-BOX B in human serum using liquid chromatography coupled to tandem mass spectrometry

Seidel

Kahnes

Bauer

et al. 2015

Journal of Chromatography B

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Section: Introductionmentioning

confidence: 60%

Section: Stabilitymentioning

confidence: 84%

Section: Purification Of Analytesmentioning

confidence: 99%

Section: Liquid Chromatography and Matrix Effectmentioning

confidence: 99%

Section: Optimization Of Mass Spectrometrymentioning

confidence: 99%

See 3 more Smart Citations

Simultaneous determination of the bilirubin oxidation end products Z-BOX A and Z-BOX B in human serum using liquid chromatography coupled to tandem mass spectrometry

Seidel

Kahnes

Bauer

et al. 2015

Journal of Chromatography B

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Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores

Ritter

Oetama

Schulze

et al. 2020

Chemistry A European J

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The degradation of chlorophyll,t he omnipresent green pigment, has been investigatedi ntensively over the last 30 years resulting in manye lucidated tetrapyrrolic degradationp roducts. With ac omparison to the degradation of the structurally similarh eme, we hereby propose an ovel additionalc hlorophyll degradation mechanism to mono-and dipyrrolic products.T his is the first proof of the occurrence of af amilyo fm ono-and dipyrrols in leaves that are previously only known as heme degradationp roducts.T his prod-uct familyi sa lso found in spit and feces of herbivores with specific metabolomic patterns reflecting the origin of the samples. Based on chromatographica nd mass spectrometric evidencea swell as on mechanistic considerations we also suggest severalt entative new degradation products.O ne of them,d ihydro BOX A, was fully confirmed as an ovel natural product by synthesis andc omparison of its spectroscopic data.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.org/10. Scheme1.Enzymatic chlorophyll degradation in plants.Scheme2.Enzymatic (top) andoxidativeheme degradation by reactive oxygen species (ROS) to PDPs and BOXes.

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All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

Dreier,

Joerk,

Uchikawa

et al. 2024

Transl. Stroke Res.

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The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical infarcts are caused by acute severe vasospastic events, so-called spreading ischemia, triggered by spontaneously occurring spreading depolarization. In locations where a spreading depolarization passes through, cerebral blood flow can drastically drop within a few seconds and remain suppressed for minutes or even hours, often followed by high-amplitude, sustained hyperemia. In spreading depolarization, neurons lead the event, and the other cells of the neurovascular unit (endothelium, vascular smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation in cells of all three supersystems—nervous, vascular, and immune—is very likely involved in the dysfunction of the neurovascular unit underlying spreading ischemia. It is assumed that subarachnoid blood, which lies directly on the cortex and enters the parenchyma via glymphatic channels, triggers these dysregulations. This review discusses the neuroglial, neurovascular, and neuroimmunological dysregulations in the context of spreading depolarization and spreading ischemia as critical elements in the pathogenesis of cortical infarcts after subarachnoid hemorrhage.

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Total Synthesis and Detection of the Bilirubin Oxidation Product (Z)-2-(3-Ethenyl-4-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide (Z-BOX A)

Cited by 21 publications

References 18 publications

Simultaneous determination of the bilirubin oxidation end products Z-BOX A and Z-BOX B in human serum using liquid chromatography coupled to tandem mass spectrometry

Simultaneous determination of the bilirubin oxidation end products Z-BOX A and Z-BOX B in human serum using liquid chromatography coupled to tandem mass spectrometry

Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores

All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

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