A new approach to the synthesis of polyunsaturated deuterated isoprostanes: Total synthesis of d4-5-epi-8,12-iso-iPF3α-VI and d4-8,12-iso-iPF3α-VI

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Chang, Chih-Tsung^1,2  Patel, Pranav^1,2  Gore, Vivek^1,2  Song, Wen-Liang^3,4  Lawson, John A.^3,4  Powell, William S.⁵  FitzGerald, Garret A.^3,4  Rokach, Joshua^1,2 

[1] Florida Inst Technol, Claude Pepper Inst, Melbourne, FL 32901 USA

[2] Florida Inst Technol, Dept Chem, Melbourne, FL 32901 USA

[3] Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA

[5] McGill Univ, Meakins Christie Labs, Dept Med, Montreal, PQ H2X 2P2, Canada

关键词: Eicosapentaenoic acid;    EPA;    Docosahexaenoic acid;    DHA;    Arachidonic acid;    AA;    Isoprostane;    iP;    Deuterated isoprostanes;   

DOI  :  10.1016/j.bmcl.2009.09.099

来源: Elsevier

【 摘 要 】

The total and stereospecific synthesis of d(4)-5-epi-8,12-iso-iPF(3 alpha)-VI 55 and d(4)-8,12-iso-iPF(3 alpha)-VI 64, EPA-derived all-syn-isoprostanes (iPs), has been accomplished. Because of issues related to volatility and yield with some of the primary deuterated synthons an improved synthesis is presented. These two deuterated analogs were used to discover and quantify the presence of the corresponding endogenous isoprostanes in human urine. These assays may serve as a valuable index of oxidative stress in population with omega-3 fatty acid enriched diets containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and may also be useful as an index of the severity of inflammatory diseases such as atherosclerosis and Alzheimer's disease. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

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