Formation of Isoprostane Bicyclic Endoperoxides from the Autoxidation of Cholesteryl Arachidonate

• Published in: Journal of the American Chemical Society Vol. 124; no. 26; pp. 7745 - 7754
• Main Authors: Yin, Huiyong, Havrilla, Christine M, Morrow, Jason D, Porter, Ned A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 03-07-2002
• Subjects: Arachidonic Acids; Chemistry; Cholesterol Esters - chemistry; Cholesterol Esters - metabolism; Exact sciences and technology; Gas Chromatography-Mass Spectrometry; Isoprostanes - chemical synthesis; Isoprostanes - chemistry; Leukotrienes - chemistry; Lipid Peroxides - chemistry; Mass spectrometry; Organic chemistry; Oxidation-Reduction; Peroxides - chemical synthesis; Peroxides - chemistry; Reactivity and mechanisms; Spectrometry, Mass, Electrospray Ionization; Autoxidation; Endoperoxide; Collisional activation; Organic hydroperoxide; Arachidonic acid derivatives; Polyunsaturated fatty acid; Fragmentation pattern; Experimental study; Degradation product; Mass spectrometry; Organic peroxide; Prostaglandin derivatives
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0201092

Autoxidation of polyunsaturated fatty acids and esters leads to a complex mixture containing hydroperoxides and cyclic peroxides. Prostaglandin bicyclic endoperoxides have been detected from the autoxidation of cholesteryl arachidonate by LC-MS and GC-MS techniques. All four possible types (I−IV) of bicyclic endoperoxides have been found starting from different regioisomeric hydroperoxides of cholesteryl arachidonate. Furthermore, the stereochemistry of Type IV bicyclic endoperoxides has been determined by conversion to pentafluorobenzyl (PFB) ester, trimethylsilyl (TMS) derivatives, and comparison with synthetic standards by the use of GC-MS. All eight possible diastereomers of the derivatized isoprostanes were observed and were separated by gas chromatography. The bicyclic endoperoxides with the two alkyl chains syn on the cyclopentane ring were formed preferentially to those with anti configuration, a result anticipated from earlier work. Substantial amounts of the anti-substituted isoprostanes, including PGF2 α, were, however, observed in the product mixture.