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

Deuteration at bis ‐allylic positions slows down hydrogen abstraction, thereby reducing the rate of polyunsaturated fatty acids (PUFA) oxidation. Arachidonic acid undergoes oxidation through both enzymatic and non‐enzymatic mechanisms, giving rise to a range of important products with variable biological 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‐D 2 ‐arachidonic acid, 10,10‐D 2 ‐arachidonic acid, 13,13‐D 2 ‐arachidonic acid, 7,7,10,10‐D 4 ‐arachidonic acid, 7,7,13,13‐D 4 ‐arachidonic acid, 10,10,13,13‐D 4 ‐arachidonic acid, and 7,7,10,10,13,13‐D 6 ‐arachidonic acid isotopologues. The library is intended to be useful for determining the relative importance of enzymatic versus non‐enzymatic oxidation at particular sites in vivo.