Epoxy phospholipids: Total synthesis, generation and in vivo detection of a new class of oxidatively truncated lipids.

摘要

Epoxy lipids are a relatively little studied class of oxidized phospholipids in comparison with their gamma-hydroxy(oxo)-alpha,beta-unsaturated analogs. Most of the known epoxy lipids were first studied in foods. Recent studies indicate that epoxy lipids are relevant to human diseases. Some of them readily form etheno adducts upon reaction with DNA's bases. These etheno adducts were detected in tissues from cancer patients. Thus it is important to know the chemistry of epoxylipid formation and their reactivity with other biomolecules. Epoxy phospholipids had not been reported. However the chemistry underlying the formation of known epoxy lipids seemed likely to produce such phospholipids. To assess the natural occurrence and biological properties of these putative epoxy phospholipids, one member of this class was prepared by total synthesis. The route developed can be easily modified to allow the production of other epoxy phospholipids. The production of the new phospholipid from oxidation of linoleic acid was demonstrated in vitro. The presence of this epoxy phospholipid was further detected in rat retina.; Extensive literature precedent suggests that 9-hydroperoxy-10,12-octadienoic acid and 13-hydroperoxy-9,11-octadienoic acid are the primary first generation oxidation products from linoleic acid. They can fragment to produce epoxy-truncated lipids, such as 4,5-epoxy-2(E)-decenal, the most studied representative of the class. Several mechanism and putative intermediates have been proposed for the formation of epoxy lipids from these lipid peroxide precursors. By examining the autoxidation of one putative intermediate, 13-hydroperoxy-9,10-cis-epoxyoctadeca-11-enoic acid, we concluded that the proposed epoxy hydroperoxide mechanism involving this intermediate is a feasible pathway for the formation of epoxy lipids.