Novel bioactive phospholipids: practical total syntheses of products from the oxidation of arachidonic and linoleic esters of 2-lysophosphatidylcholine(1).
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 gamma-keto-alpha,beta-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.
Sun
Mingjiang
M
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106-7078, USA.
Deng
Yijun
Y
Batyreva
Eugenia
E
Sha
Wei
W
Salomon
Robert G
RG
D016718:Arachidonic Acid / Q000737:chemistry*; D008041:Linoleic Acids / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000138:chemical synthesis / Q000737:chemistry*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000138:chemical synthesis*
D008041:Linoleic Acids; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D016718:Arachidonic Acid