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Total Syntheses of Two bis‐Allylic‐Deuterated DHA Analogues
Author(s) -
Rosell Mélissa,
Villa Maxime,
Durand Thierry,
Galano JeanMarie,
Vercauteren Joseph,
Crauste Céline
Publication year - 2017
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201600565
Subject(s) - chemistry , polyunsaturated fatty acid , allylic rearrangement , lipid peroxidation , deuterium , docosahexaenoic acid , aldehyde , adduct , organic chemistry , fatty acid , enzyme , catalysis , physics , quantum mechanics
The deuteration of polyunsaturated fatty acids (PUFAs) at their bis‐allylic positions is known to limit harmful lipid peroxidation, which leads to the damage of cell membranes. Therefore, to impede toxic lipid peroxidation in retina tissue, we have designed and synthesized two deuterated analogues of docosahexaenoic acid (DHA; C22:6, n ‐3), which is the main lipid constituent of retina membranes. To avoid its oxidative degradation into toxic carboxyethylpyrrole (CEP) adducts, whilst preserving enzymatic metabolization into a healthy neuroprotectine derivative (NPD1), deuterium was incorporated at specific 6‐ and 6,9‐bis‐allylic positions. A convergent synthetic strategy, based on a Wittig olefination, was developed to obtain both deuterated DHA species. Common aldehyde intermediates were synthesized from another PUFA, eicosapentaenoic acid (EPA; C20:5, n ‐3). Deuterium atoms were introduced through either the reduction of an ester with a deuterated reagent or a nucleophilic reaction with deuterated paraformaldehyde.