Development of a Unified Synthetic Approach to the Oxidation Products of
Bilirubin
Taufiqueahmed Mujawar a
; Petr Sevelda a
; Jakub Švenda* a, b
a
Masaryk University, Faculty of Science, Department of Chemistry, Kamenice 5/A8, 623 00
Brno, Czech Republic
b
International Clinical Research Center, St. Anne’s University Hospital Brno, Pekařská 53, 656 91
Brno, Czech Republic
mtaufiqueahmed@sci.muni.cz; svenda@chemi.muni.cz
Yellow pigment bilirubin is the well-known primary product of heme catabolism.1
It is
a powerful antioxidant2
and a potent signaling molecule3
with multiple speculated biological
functions. When exceeding safe levels in the blood, particularly during the neonatal period,
severe hyperbilirubinemia can result and lead to neurotoxicity accounting for some instances
of neonatal morbidity and mortality.4
Despite the worldwide use of phototherapy and numerous
scientific studies thereof, there remain important unanswered questions. Bilirubin is a potent
antioxidant and gives rise to various products of (photo)oxidation.5–7
Standards of such
bilirubin-derived products are needed for studies of their inherent bioactivities and mechanisms
of formation. Unfortunately, accessing these in sufficient quantities and purity is often
problematic. The main objective of our work is to develop a unified synthetic platform that will
deliver all major classes of bilirubin-derived oxidation products. Recently, the approach
featuring pre-functionalized building blocks and metal-catalyzed transformations has allowed
us to prepare simple and complex products of oxidative degradation of bilirubin.
Keywords: bilirubin, (photo)oxidation products, chemical synthesis
References:
(1) Lightner, D. A. Bilirubin: Jekyll and Hyde Pigment of Life; Springer, 2013.
(2) Stocker, R.; Yamamoto, Y.; McDonagh, A. F.; Glazer, A. N.; Ames, B. N. Science 1987, 235, 1043–1046.
(3) Vítek, L. Med. Res. Rev. 2020, 40, 1335–1351.
(4) Wagner, K. H.; Wallner, M.; Mölzer, C.; Gazzin, S.; Bulmer, A. C.; Tiribelli, C.; Vitek, L. Clin. Sci. 2015,
129, 1–25.
(5) Clark, J. F.; Sharp, F. R. J. Cereb. Blood Flow Metab. 2006, 26, 1223–1233.
(6) Bonnett, R.; Dimsdale, M. J.; Stephenson, G. F. J. Chem. Soc. Perkin Trans. 1 1987, 439–443.
(7) Yamaguchi, T.; Shioji, I.; Sugimoto, A.; Komoda, Y.; Nakajima, H. J. Biochem. 1994, 116, 298–303.
NH HN
HNNH
H3C
HO2C CO2H
CH3
H3C
CH3
O O
Bilirubin