Synthesis of Resolvin E1

Resolvins, protectins and maresins are exquisitely potent cell signaling molecules derived from the omega-3-fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA). These oxidative metabolites like Resolvin E1 (Figure 1) are synthesized on-demand via lipoxygenase and cyclooxygenase in tissues as a protective response to acute inflammatory insults. They play a key role in restoring homeostasis by limiting neutrophil tissue infiltration, counter regulating production of chemokines and cytokines, and stimulating M2 macrophage polarization¹. As critical regulators on inflammatory response, SPMs have tremendous potential in numerous diseases including asthma², rheumatoid arthritis³, lupus⁴, atherosclerosis⁵, psoriasis⁶, heart ischemia⁷ and bacterial infections⁸.

Despite the importance of these bioactive molecules, research has been limited by compound availability. Current synthetic methods typically require more than twenty steps and are plagued with reactions that give mixtures of isomers and require tedious purifications. Chemists at NEDP have already completed the total synthesis of several SPMs on gram scale and are now optimizing them for large scale production. The material generated from these proprietary processes will be used to support clinical development of several drug products where SPMs are the API (Active pharmaceutical Ingredient).