On the Products of Cholesterol Autoxidation in Phospholipid Bilayers and the Formation of Secosterols Derived Therefrom.

In homogenous solution, cholesterol autoxidation leads to a mixture of epimers of 5 primary products, whose concentrations vary in the presence/absence of antioxidants, such as vitamin E. Two of the products (5α-OOH and 6β-OOH) undergo Hock fragmentation to yield electrophilic secosterols implicated in disease. Herein, we show that the product distribution is similar in phospholipid bilayers, in that the 7-OOHs are the major products, but the presence/absence of vitamin E has no effect on the distribution. Cholesterol 7α-OOH, but not 7β-OOH, undergoes Hock fragmentation to yield a mixture of unprecedented A-ring cleavage products and 6,7-epoxides. When subjected to typical derivatization conditions, 7α-OOH yields products with essentially indistinguishable chromatographic and spectroscopic features from the previously identified secosterols, casting further doubt on their controversial origin from endogenous O3 .