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.
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