Synthesis and Antimicrobial Activity of Burkholderia -Related 4-Hydroxy-3-methyl-2-alkenylquinolines (HMAQs) and Their N -Oxide Counterparts - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Natural Products Année : 2020

Synthesis and Antimicrobial Activity of Burkholderia -Related 4-Hydroxy-3-methyl-2-alkenylquinolines (HMAQs) and Their N -Oxide Counterparts

Résumé

The Burkholderia genus offers a promising potential in medicine because of the diversity of biologically active natural products encoded in its genome. Some pathogenic Burkholderia spp. biosynthesize a specific class of antimicrobial 2-alkyl-4(1H)-quinolones, i.e., 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs) and their N-oxide derivatives (HMAQNOs). Herein, we report the synthesis of a series of six HMAQs and HMAQNOs featuring a trans-Δ2 double bond at the C2-alkyl chain. The quinolone scaffold was obtained via the Conrad-Limpach approach, while the (E)-2-alkenyl chain was inserted through Suzuki-Miyaura cross-coupling under microwave radiation without noticeable isomerization according to the optimized conditions. Subsequent oxidation of enolate-protected HMAQs cleanly led to the formation of HMAQNOs following cleavage of the ethyl carbonate group. Synthetic HMAQs and HMAQNOs were evaluated in vitro for their antimicrobial activity against different Gram-negative and Gram-positive bacteria as well as against molds and yeasts. The biological results support and extend the potential of HMAQs and HMAQNOs as antimicrobials, especially against Gram-positive bacteria. We also confirm the involvement of HMAQs in the autoregulation of the Hmq system in Burkholderia ambifaria.
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Dates et versions

hal-03590620 , version 1 (28-02-2022)

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Marianne Piochon, Pauline Coulon, Armand Caulet, Marie-Christine Groleau, Eric Déziel, et al.. Synthesis and Antimicrobial Activity of Burkholderia -Related 4-Hydroxy-3-methyl-2-alkenylquinolines (HMAQs) and Their N -Oxide Counterparts. Journal of Natural Products, 2020, 83 (7), pp.2145-2154. ⟨10.1021/acs.jnatprod.0c00171⟩. ⟨hal-03590620⟩

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