2-(2-Heptenyl)-3-methyl-4-quinolinol from a Pseudomonas

Hashimoto, Masashi; Hattori, Kiyoshi

doi:10.1248/cpb.15.718

Cited by 18 publications

(16 citation statements)

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“…Pleasingly, we found that decreasing the reaction time and temperature to one minute and 70 °C, respectively, avoided isomerization while still allowing full conversion of the starting material (entries 4 to 6). Analytical (HRMS) and spectral ( 1 H and 13 C NMR, Tables 2 and 3) data of HMAQ 1, [18][19][20][21][22]24,25,27 HMAQ 2 (burkholone), 28 and HMAQ 3 19,20,26,27 were in excellent agreement with those published for the isolated natural products.…”

Section: Scheme 2 Synthesis Of 2-(chloromethyl)-quinolone 17 Via Consupporting

confidence: 77%

“…biosynthesize a specific class of AQs, namely 4-hydroxy-3-methyl-2alkenylquinolones (HMAQ, 1-3), which feature a methyl group at C3 and a trans- 2 insaturation at the C2-alkyl chain (Figure 1). [17][18][19][20][21][22][23][24][25][26][27] HMAQs 1 and 3, respectively the heptenyl and nonenyl congeners, exhibit potent antifungal 19,20,22,24,25 and antibacterial 19,27 activities against diverse microorganisms as well as plant growth promoting activities. 22 Furthermore, HMAQs 1 and 3 act confirmation of structural identities and biological activities as well as for sustaining drug discovery and pharmaceutical development.…”

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confidence: 99%

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

Piochon¹,

Coulon²,

Caulet³

et al. 2020

Preprint

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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., 4hydroxy-3-methyl-2-alkenylquinolones (HMAQs) and their N-oxide derivatives (HMAQNOs).Herein, we report the synthesis of a series of six HMAQs and HMAQNOs featuring a trans- 2 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 in vitro evaluated for their antimicrobial activity against different Gram-negative and Gram-positive bacteria as well as against fungi 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. The Burkholderia genus includes a vast group of Gram-negative bacteria found in diverse ecological niches. 1,2 Some Burkholderia spp. are of serious pathogenic concerns, such as the Centers for Disease Control and Prevention (CDC) Tier 1 select agents 3 Burkholderia pseudomallei and B. malleithe infectious agents of melioidosis 4,5 and glanders, 6 respectively,and the devastating plant crop pathogens B. glumae and B. gladioli, which cause major yield losses in rice productions. 7,8 Others, like those forming the B. cepacia complex, include species that can both live in beneficial associations with their eukaryotic hots (mammals, plants, and fungi) 2 and cause several hard-to-treat opportunistic infections, such as the cepacian syndrome in individuals suffering from cystic fibrosis. 9Burkholderia spp. offer a tantalizing potential in medicine because of their capacity to produce highly potent and structurally diverse metabolites. 10,11 A plethora of natural products exhibiting various biological functions have been identified or isolated so far from Burkholderia spp. 10 To name few examples, only for B. pseudomallei, cytotoxic siderophores (e.g., malleilactone), 12 proteasome inhibitors (e.g., deoxyglidobactin C), 13 tensioactive lipopeptides (e.g., malleipeptin A), 13 and rhamnolipids, 14 as well as quorum sensing modulators such as N-acyl homoserine lactones (AHLs) 15 and 2-alkyl-4(1H)-quinolones (AQs) 16,17 have been reported.Burkholderia spp. biosynthesize a specific class of AQs, namely 4-hydroxy-3-methyl-2alkenylquinolones (HMAQ, 1-3), which feature a methyl group at C3 and a trans- 2 insaturation at the C2-alkyl chain (Figure 1). [17][18][19][20][21][22][23][24][25][26][27] HMAQs 1 and 3, respectively the heptenyl and nonenyl congeners, exhi...

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Section: Scheme 2 Synthesis Of 2-(chloromethyl)-quinolone 17 Via Consupporting

confidence: 77%

mentioning

confidence: 99%

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

Piochon¹,

Coulon²,

Caulet³

et al. 2020

Preprint

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“…Because these structural elements accounted for six out of eight degrees of unsaturation, the remaining two degrees correspond to two rings, which constitutes a fused bicyclic structure as suggested by the number of available aromatic carbons (eleven). A 4-quinolone substructure was indicated by a peak-splitting at the 340–320 nm region in the UV spectrum (328 and 322 nm) [ 13 ]. Indeed, 1 H NMR resonances at the down field region was superimposable on those of known 2-heptyl-4(1 H )-quinolone ( 2 , Supporting Information File 1 , Figure S11).…”

Section: Resultsmentioning

confidence: 99%

“…The remaining metabolites were identified as known compounds based on NMR and MS data (data not shown). Compound 2 was identified as Pyo Ib or 2-heptylquinolin-4(1 H )-one [ 16 ], 4 was identified as ( E )-2-(hept-2-en-1-yl)-3-methylquinolin-4(1 H )-one [ 13 ], 5 was identified as PSC-C or 2-heptyl-3-methylquinolin-4(1 H )-one [ 17 ], 6 was identified as PSC-D or ( E )-3-methyl-2-(non-2-en-1-yl)quinolin-4(1 H )-one) [ 17 ], 7 was identified as pyrrolnitrin [ 18 ], and 8 was identified as BN-227 [ 19 ] ( Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

Li¹,

Oku²,

Hasada³

et al. 2018

Beilstein J. Org. Chem.

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Exploration of rhizobacteria of the genus Burkholderia as an under-tapped resource of bioactive molecules resulted in the isolation of two new antimicrobial 2-alkyl-4-quinolones. (E)-2-(Hept-2-en-1-yl)quinolin-4(1H)-one (1) and (E)-2-(non-2-en-1-yl)quinolin-4(1H)-one (3) were isolated from the culture broth of strain MBAF1239 together with four known alkylquinolones (2 and 4–6), pyrrolnitrin (7), and BN-227 (8). The structures of 1 and 3 were unambiguously characterized using NMR spectroscopy and mass spectrometry. Compounds 1–8 inhibited the growth of the marine bacterium Tenacibaculum maritimum, an etiological agent of skin ulcers in marine fish, offering new opportunities to develop antibacterial drugs for fish farming.

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“…After a detailed analysis of the literature, we were able to find that bacterially produced methylated HAQs with an unsaturated aliphatic side chain had been detected previously. 4-Hydroxy-3-methyl-2-heptenylquinoline from an uncharacterized Pseudomonas strain was identified (24) and was later found in various B. cepacia (unidentified genomovar) strains (48) along with HMNQ (27) and a series of congeners from family B (41). As with P. aeruginosa HAQs, HMAQs are produced as mixtures of various congeners with an alkyl chain of variable length with or without an unsaturation and/or an Noxide function on their quinoline amino group.…”

Section: Discussionmentioning

confidence: 99%

Burkholderia pseudomallei,B. thailandensis, andB. ambifariaProduce 4-Hydroxy-2-Alkylquinoline Analogues with a Methyl Group at the 3 Position That Is Required for Quorum-Sensing Regulation

et al. 2008

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4-Hydroxy-2-alkylquinolines (HAQs), especially 3,4-dihydroxy-2-heptylquinoline (Pseudomonas quinolone signal) and its precursor, 4-hydroxy-2-heptylquinoline, are attracting much attention, mainly because of their role as signaling molecules in Pseudomonas aeruginosa. The pqsABCDE operon is centrally involved in their biosynthesis. The presence of a homologous operon in Burkholderia pseudomallei and B. thailandensis was recently reported. Thus, we have investigated the abilities of 11 Burkholderia species to produce HAQ-like molecules by liquid chromatography/mass spectrometry. We have identified 29 different HAQ derivatives produced by the only three Burkholderia species where a pqsABCDE homologue was found among available sequenced Burkholderia species genomes, including B. ambifaria, a member of the Burkholderia cepacia complex. In contrast with those of P. aeruginosa, Burkholderia HAQs typically bear a methyl group, hence their designation as 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs). We identified three families of HMAQs with a saturated or unsaturated alkyl chain at the 2 position, in contrast with the 1 position of P. aeruginosa, including one with an N-oxide group. Furthermore, the operon in these species contains two more genes downstream of the pqsE homologue, resulting in the hmqABCDEFG operon. While the inactivation of hmqA inhibits the production of HMAQs, the methylation of the quinoline ring requires a putative methyltransferase encoded by hmqG. Interestingly, hmqA or hmqG mutations increase the production of acyl homoserine lactones and, consequently, phenotypes under the control of quorum sensing in B. ambifaria: antifungal activity, siderophore production, and proteolytic activity. These results indicate that only HAQs bearing a methyl group (HMAQs) are involved in quorum-sensing regulation.

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2-(2-Heptenyl)-3-methyl-4-quinolinol from a Pseudomonas

Cited by 18 publications

References 0 publications

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

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

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

Burkholderia pseudomallei,B. thailandensis, andB. ambifariaProduce 4-Hydroxy-2-Alkylquinoline Analogues with a Methyl Group at the 3 Position That Is Required for Quorum-Sensing Regulation

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