Total synthesis of Resolvin E1

• Published in: Tetrahedron letters Vol. 52; no. 21; pp. 2623 - 2626
• Main Authors: Allard, Melissa, Barnes, Keith, Chen, Xuemei, Cheung, Yiu-Yin, Duffy, Bryan, Heap, Charles, Inthavongsay, John, Johnson, Matthew, Krishnamoorthy, Ravi, Manley, Chris, Steffke, Stephan, Varughese, Deepu, Wang, Ruifang, Wang, Yi, Schwartz, C.E.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 25.05.2011; Elsevier
• Subjects: Aliphatic compounds; Chemistry; Chemistry, Organic; Disengaging; Enantioselective synthesis; Exact sciences and technology; Inflammation resolution; Ketones; Modular; Organic chemistry; Physical Sciences; Precursors; Preparations and properties; Reduction; Resolvin E1; Science & Technology; Synthesis (chemistry); Takai and Sonogashira couplings; Tetrahedrons; Total synthesis; Takai and Sonogashira couplings; Resolvin E1; Inflammation resolution; Enantioselective synthesis; Total synthesis; ASYMMETRIC TRANSFER HYDROGENATION; INFLAMMATION; SYSTEMS-APPROACH; RESOLUTION; LIPID MEDIATORS; ASPIRIN; Acetylenic compound; Enantioselectivity; Inflammation; Oxygen heterocycle; Ketone; Chemical reduction; Sonogashira coupling; Alkene; Polyenic compound; Analog; Takai olefination; Chemical synthesis; Ethylenic compound; Alkyne
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2011.03.035

The enantioselective total synthesis of Resolvin E1 (RvE1), a naturally occurring small molecule mediator of inflammation resolution, is reported. Two routes are presented, both modular and convergent in nature, with an excellent control of all stereocenters. The C12- and C18-hydroxy groups are derived from (S)-glycidol while the C5-hydroxy group is installed via enantioselective reduction of a ketone precursor. Both the cis-alkenes are introduced with excellent control by the reduction of a late-stage bis-alkyne intermediate. The synthetic disconnections are very amenable to analog preparation, and further modifications to the chemistry have allowed for scale-up and First in Man testing of this novel pro-resolution molecule.