52] Synthesis of inflammatory signal transduction species formed during ozonation and/or peroxidation of tissue lipids

Abstract

Lipid peroxidation and ozonation produce oxidized lipids that are bioactive and can act as signal transducers. The synthesis and isolation of these oxidized lipid products in pure form will allow the testing of hypotheses regarding their role as potential relay molecules. Of special interest are oxidized lipids derived from 1,2-diacyl- sn -glycero-3-phosphocholine that feature a shortened acyl chain on the second position ending with an aldehyde function. These platelet-activating factor analogs are not only produced during ozonation but also during the peroxidation of 1,2-diacyl- sn -glycero-3-phosphocholines. Another class of biologically active lipids is the 1-hydroxy-l-hydroperoxyalkanes formed in vivo from the addition of water to the carbonyl oxides that are intermediates in the ozonation of unsaturated lipids in aqueous media. 1-Hydroxy-1-hydroperoxyalkanes are conveniently generated in situ from the hydrolysis of bis(1-hydroxyalkyl) peroxides. Bis(1-hydroxyalkyl)peroxides are not themselves direct lipid ozonation products, but are stable crystalline compounds that slowly hydrolyze to the corresponding 1-hydroxy-1-hydroperoxyalkanes and aldehydes. This chapter reports the syntheses of 1-palmitoyl-2-[3-(8-octanoyl)-5-(1-octyl)-l,2,4-trioxolane]- sn -glycero-3-phosphocholine (the Criegee ozonide of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), 1-palmitoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine, 1-palmitoyl-2-(1-hydroxy-1-hydroperoxynonanoyl)- sn -glycero-3-phosphocholine, bis(1-hydroxyheptyl) peroxide, and bis(1-hydroxynonyl)peroxide (the percursors of the corresponding 1-hydroxy-1-hydroperoxyalkanes).