A Platform for the Synthesis of Oxidation Products of Bilirubin

Abstract

Bilirubin is the principal product of heme catabolism. High concentrations of the pigment are neurotoxic, yet slightly elevated levels are beneficial. Being a potent antioxidant, oxidative transformations of bilirubin occur in vivo and lead to various oxidized fragments. The mechanisms of their formation, intrinsic biological activities, and potential roles in human pathophysiology are poorly understood. Degradation methods have been used to obtain samples of bilirubin oxidation products for research. Here, we report a complementary, fully synthetic method of preparation. Our strategy leverages repeating substitution patterns in the parent tetracyclic pigment. Functionalized ready-to-couple γ-lactone, γ-lactam, and pyrrole monocyclic building blocks were designed and efficiently synthesized. Subsequent modular combinations, supported by metal-catalyzed borylation and cross-coupling chemistries, translated into the concise assembly of the structurally diverse bilirubin oxidation products (BOXes, propentdyopents, and biopyrrins). The discovery of a new photoisomer of biopyrrin A named lumipyrrin is reported. Synthetic bilirubin oxidation products made available in sufficient purity and quantity will support future in vitro and in vivo investigations.

meso-Aryl substituents modify the electrochemical profile and palladium(ii) coordination of redox-active tripyrrin ligands

“…Synthetic methods to prepare the naturally occurring biopyrrins have only become available very recently, 29 and all tripyrrindione complexes reported to date have featured ethyl or methyl β-substituents on the pyrrole rings (Fig. 1).…”

Molecule Engineering Metal–Organic Framework-Based Organic Photoelectrochemical Transistor Sensor for Ultrasensitive Bilirubin Detection

“…Bilirubin (Bil) is a kind of hydrophobic byproduct of the metabolism of hemoglobin, serving as an important clinical diagnostic marker for various conditions such as hemolytic diseases, liver dysfunction, biliary tract diseases, and colorectal cancer. , It is typically classified into three major categories: direct bilirubin, indirect bilirubin (I-Bil, also known as free bilirubin), and total bilirubin. , Elevated I-Bil levels, particularly in the serum, serve as a warning indicator for hepatic injury, cirrhosis, neonatal jaundice, cholestasis, aplastic anemia, or primary malignancies. Therefore, monitoring the I-Bil concentration is crucial for the early diagnosis and treatment of diseases.…”