Improved Synthesis of the C16–C20 Segment of Resolvin E1 Using Enantioselective Ketone Reduction and Lipase-Catalyzed Resolution

A practical synthesis targeting the C16–C20 segment of the endogenous metabolite Resolvin E1 (RvE1) is described. The original route was revised to avoid the use of source-constrained raw materials and chemistries that were problematic on larger scale. The revised route utilizes commercially available ( E )-1-chloropent-1-en-3-one as the key raw material to replace ( S )-glycidol. The ( E )-vinyl iodide functionality was installed by an addition/elimination sequence to prepare the segment required for a subsequent Sonogashira coupling. The chiral secondary hydroxyl group at C18 was established by Corey–Bakshi–Shibata (CBS) reduction followed by lipase-catalyzed acetylation to achieve chiral purity in excess of 98% ee. The revised route offered a viable multikilogram process to support early clinical production of this pro-resolution therapeutic agent.