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

Lukas Trippe; Analuisa Nava; Andrea Frank; Dieter Schollmeyer; Udo Nubbemeyer

doi:10.1055/a-1512-1763

Synthesis, Inhaltsverzeichnis

Synthesis 2021; 53(20): 3760-3768
DOI: 10.1055/a-1512-1763

paper

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

Lukas Trippe

^aOrganische Chemie/Johannes Gutenberg-Universität Mainz, Duesbergweg 10–14, 55128 Mainz, Germany

,

Analuisa Nava

^bBASF Lampertheim GmbH, Chemiestr. 22, 68623 Lampertheim, Germany

,

Andrea Frank

^aOrganische Chemie/Johannes Gutenberg-Universität Mainz, Duesbergweg 10–14, 55128 Mainz, Germany

,

Dieter Schollmeyer

^aOrganische Chemie/Johannes Gutenberg-Universität Mainz, Duesbergweg 10–14, 55128 Mainz, Germany

,

Udo Nubbemeyer∗

^aOrganische Chemie/Johannes Gutenberg-Universität Mainz, Duesbergweg 10–14, 55128 Mainz, Germany

› Institutsangaben

Abstract

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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

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Zusatzmaterial

Supporting Information