Novel Bioactive Phospholipids: Practical Total Syntheses of Products from the Oxidation of Arachidonic and Linoleic Esters of 2-Lysophosphatidylcholine1
journal contributionposted on 07.05.2002, 00:00 by Mingjiang Sun, Yijun Deng, Eugenia Batyreva, Wei Sha, Robert G. Salomon
Total syntheses of nine novel phospholipids were accomplished to facilitate the identification and biological testing of compounds that are generated upon oxidative cleavage of arachidonate and linoleate esters of 2-lysophosphatidylcholine, the two most abundant polyunsaturated phospholipids in low-density lipoprotein. An efficient general synthesis exploiting 2-lithiofuran as a 4-oxo-2-butenoyl carbanion equivalent provided phospholipids containing γ-keto-α,β-unsaturated carbonyl functional arrays. By exploiting facile cis−trans isomerizations, two commercially available cis alkenes, (2Z)-2-butene-1,4-diol and 2,5-dihydrofuran, could be employed as starting materials for preparing the Horner−Wadsworth−Emmons reagent 4-(diethoxyphosphoryl)-2E-butenal, a valuable building block for the synthesis of 2,4-dienals. The reagent was exploited in a total synthesis of 13-oxotridec-9E,11E-dienoic acid, confirming the identity of this product that is generated upon autoxidation of linoleic acid and by decomposition of 13-hydroperoxy-9,11-octadecadienoate (13-HPODE), especially in the presence of redox active transition metal ions, cytochrome p-450, or hydroperoxide lyase.