Synthesis of Enantiopure ω-(4-Fluorophenyl)-6,11-Methylene Lipoxin B₄ Methyl Ester

Abstract

The synthesis of Lipoxin B₄ analogues (LXB₄) to gain access to stabilized inflammation-resolving compounds is an active field of research. Focusing on variation and stabilization of the conjugated E,Z,E,E C6–C13 tetraene moiety of natural LXB₄, a methylene bridge introduced between C6 and C11 suppresses any Z/E isomerization of the C8–C9 olefin. Furthermore, rapid ω-oxidation (C20) should be avoided by replacing the C18–C20 segment by an aromatic moiety. Optically active C1–C12 building blocks were accessed from methyl cycloheptatriene-1-carboxylate (C6–C11, C21) and glutaryl chloride (C1–C5) as described earlier. The ω-segment was generated via a five-step sequence starting from 4-arylbutanoic acid. Horner key olefination enabled assembly of the carbon backbone. A final five-step sequence including a chelate Cram reduction of the unsaturated ketone moiety afforded the target ω-aryl 6,11-methylene-LXB₄ methyl ester.

Key words

lipoxin B₄ analogue - convergent total synthesis - Horner olefination - optically active β-ketophosphonate - diastereoselective reduction

Publikationsverlauf

Eingereicht: 21. April 2021

Angenommen: 19. Mai 2021

Accepted Manuscript online:
19. Mai 2021

Artikel online veröffentlicht:
15. Juni 2021

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