On the Origin of Secosterols Upon Oxidation of Cholesterol

Title: On the Origin of Secosterols Upon Oxidation of Cholesterol
Authors: Zopyrus, Nadia
Date: 2017
Abstract: Cholesterol is one of the most abundant lipids in the body, and like all unsaturated lipids, it can be oxidized by a variety of reactive oxygen species (ROS). Lipid peroxidation is one of the main pathways by which ROS induce oxidative damage, and has been linked to neurodegenerative and cardiovascular diseases. In 2003, Wentworth et al. detected both 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A) and its intramolecular aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxaldehyde (secosterol-B) in human atherosclerotic plaques – compounds which, at the time, were only known to be formed by cholesterol ozonolysis. However, our group has shown that cholesterol 5α-hydroperoxide, which is the product of the reaction of cholesterol with singlet oxygen, can undergo acid-catalyzed Hock fragmentation to generate secosterol-A and -B as well. Nevertheless, cholesterol 5α-hydroperoxide readily rearranges to a more thermodynamically stable cholesterol 7-hydroperoxide. Herein we show that cholesterol 7-hydroperoxide, the main product of cholesterol autoxidation, can also undergo acid-catalyzed Hock fragmentation that gives rise to electrophilic species with similar chromatographic characteristics to those that were allegedly identified as secosterol-A and -B. We also proposed to prepare authentic products of the Hock fragmentation of cholesterol 7-hydroperoxide by subjecting Δ⁶’⁷-cholesterol to ozonolysis. Herein, we explore the limitations and complications of Δ⁶’⁷-cholesterol ozonolysis as well as cholesterol 7-OOH Hock fragmentation which both resulted in unexpected (unprecedented) products.
URL: http://hdl.handle.net/10393/35885
CollectionThèses, 2011 - // Theses, 2011 -