A Platform for the Synthesis of Oxidation Products of Bilirubin

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Authors

MUJAWAR Taufiqueahmed Pirsaheb SEVELDA Petr MADEA Dominik KLÁN Petr ŠVENDA Jakub

Year of publication 2024
Type Article in Periodical
Magazine / Source Journal of the American Chemical Society
MU Faculty or unit

Faculty of Science

Citation
Web https://pubs.acs.org/doi/10.1021/jacs.3c11778
Doi http://dx.doi.org/10.1021/jacs.3c11778
Keywords Alkyls; Cross coupling reaction; Organic compounds; Pyrroles; Reaction products
Attached files
Description 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 gamma-lactone, gamma-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.
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