Full Library of (Bis–allyl)-deuterated Arachidonic Acids: Synthesis and Analytical Verification

摘要

Deuteration at bis-allylic positions slows down hydrogen ab- straction, thereby reducing the rate of polyunsaturated fatty acids (PUFA) oxidation. Arachidonic acid undergoes oxidation through both enzymatic and non-enzymatic mechanisms, giv- ing rise to a range of important products with variable bio- logical activity, including pro- and anti-inflammatory properties. We report on the synthesis and verification of a full library of arachidonic acids variably deuterated at the bis-allylic (C7, C10, C13) positions: 7,7-D2-arachidonic acid, 10,10-D2-arachidonic acid, 13,13-D2-arachidonic acid, 7,7,10,10-D4-arachidonic acid, 7,7,13,13-D4-arachidonic acid, 10,10,13,13-D4-arachidonic acid, and 7,7,10,10,13,13-D6-arachidonic acid isotopologues. The li- brary is intended to be useful for determining the relative im- portance of enzymatic versus non-enzymatic oxidation at par- ticular sites in vivo.