On the Total Synthesis of 7,8(S,S)-Epoxy-17(S)-hydroxy-4(Z),9(E),11(E),13(Z),15(E),19(Z)-docosahexaenoic Acid Derivative
Robert Nshimiyimana, Charles N. Serhan, Nicos A. Petasis
TL;DR
This paper describes the synthesis of a complex fatty acid derivative that is a precursor to important biological molecules involved in tissue regeneration.
Contribution
The paper presents a stereoselective total synthesis of a biologically relevant epoxy fatty acid derivative.
Findings
A Sharpless enantioselective epoxidation was used to install the oxirane unit.
Wittig coupling reactions were key in forming the correct alkenyl configuration.
The synthesized acid is a precursor to resolvins and other pro-resolving mediators.
Abstract
The stereoselective total synthesis of an allylic epoxide-containing polyunsaturated fatty acid, in its triethylsilyl (TES) ether and methyl ester form, is described. Key features include a Sharpless enantioselective epoxidation to install the oxirane unit and Wittig coupling reactions to forge critical alkenyl configuration and secure the core carbon skeleton. The deprotected epoxy acid was recently demonstrated to play a central role as the precursor to biologically active resolvins D1, D2, and the cysteinyl conjugate in tissue regeneration (RCTR1) by human leukocytes. These natural products belong to a family of cell signaling molecules termed specialized pro-resolving mediators (SPMs).
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Taxonomy
TopicsEicosanoids and Hypertension Pharmacology · Fatty Acid Research and Health · Advanced Glycation End Products research