Total synthesis and characterization of the bilirubin oxidation product (Z)-2-(4-ethenyl-3-methyl-5-oxo-1,5-dihydro-2H-pyrrol-2-ylidene)ethanamide (Z-BOX B)

Impact of higher-order heme degradation products on hepatic function and hemodynamics

“…Preparation of BOXes Z-BOX A and Z-BOX B were prepared via in vitro bilirubin oxidation and chemical synthesis as described. 19,20 Isomer purity was confirmed by liquid chromatography, coupled to tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance spectroscopy. Water solubility and partition constants (1-octanol/ water) were determined spectrophotometrically.…”

“…15,16 However, systematic assessment of the role of these higher-order degradation products was hampered so far by a lack of analytical tools and BOXes of appropriate purity. [16][17][18] To enable the systematic assessment of biological fate and function, we recently established syntheses, 19,20 purification, and sensitive analytics of Z-BOX A and B. 21 Given the central role of the liver in heme degradation, we studied pharmacokinetics and -dynamics of Z-BOX A and B and explored their impact on hepatic function.…”

Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores

“…To avoid this, sodium hydroxide in methanol was used with 10 % hydrogen peroxide, which resulted in higher amounts of degradation products. With this optimized method, we could prove by UHPLC/HR‐MS and the addition of standards the occurrence of PDP B1/B2 as well as of BOX A, B, C and hematinic acid (HA) as degradation products of Chl a in vitro (Scheme , see Supporting Information, Figures S7–S12). The finding of BOX A seems surprising, considering that the corresponding part of Chl holds an ethyl instead of a vinyl group.…”

“…Following the published synthesis of BOX A, dihydro BOX A was synthesized and fully characterized . Starting from methyl‐( Z )‐2‐(3‐bromo‐4‐methyl‐5‐oxo‐1,5‐di‐hydro‐2 H ‐pyrrol‐2‐ylidene)ethanoate ( 1 ) the synthesis of dihydro BOX A succeeds through four synthetic steps with a total yield of 64 % (Scheme ).…”

“…Purification of standards: PDPs, BOX C and hematinic acid were purified from bilirubin oxidation according to published protocols . BOX A and B were synthesized as published …”