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Synthesis and Biological Evaluation of Bicyclo[1.1.1]pentane-Containing Aromatic Lipoxin A₄ Analogues.

ABSTRACT: Lipoxins are important drivers of inflammation resolution, suggesting a potential therapeutic benefit. Bicyclo[1.1.1]pentanes (BCPs) are potential isosteric replacements for arenes and/or alkyl groups within drug candidates. We carried out an asymmetric synthesis of four BCP-containing synthetic lipoxin A₄ mimetics (BCP-sLXms) in which the key steps were a Suzuki coupling, an asymmetric ketone reduction, and a triethylborane-initiated radical bicyclopentylation. These mimetics were screened for their impact on inflammatory responses, and one imidazolo-BCP-sLXm (6a) was found to possess high anti-inflammatory activity.

SUBMITTER: Owen B

PROVIDER: S-EPMC9400386 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Synthesis and Biological Evaluation of Bicyclo[1.1.1]pentane-Containing Aromatic Lipoxin A4 Analogues.

Owen Benjamin B de Gaetano Monica M Gaffney Andrew A Godson Catherine C Guiry Patrick J PJ

Organic letters 20220808 32

Lipoxins are important drivers of inflammation resolution, suggesting a potential therapeutic benefit. Bicyclo[1.1.1]pentanes (BCPs) are potential isosteric replacements for arenes and/or alkyl groups within drug candidates. We carried out an asymmetric synthesis of four BCP-containing synthetic lipoxin A4 mimetics (BCP-sLXms) in which the key steps were a Suzuki coupling, an asymmetric ketone reduction, and a triethylborane-initiated radical bicyclopentylation. These mimetics were sc ...[more]

PMID: 35938947

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