Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

Lewis, Wilfred J. M.; Shaw, David M.; Robertson, Jeremy

doi:10.3762/bjoc.17.31

Cited by 5 publications

(1 citation statement)

References 41 publications

(31 reference statements)

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“…Detailed mechanisms and molecular targets of the new metabolites remain to be elucidated. Such experiments have so far been hampered by the fact that no total synthesis for the metabolites is established (organic synthesis reported only for azetidomonamide B and pyrrolizidines legonmycin A/ B), 10,36 and that, due to their relatively small size, options for functionalization for, for example, photoaffinity labeling is limited. Considering the effect on biofilm formation, it could be speculated that aze metabolites contribute to the transition from acute to chronic infection.…”

Section: ■ Conclusion and Outlookmentioning

confidence: 99%

Azetidomonamide and Diazetidomonapyridone Metabolites Control Biofilm Formation and Pigment Synthesis in Pseudomonas aeruginosa

et al. 2022

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Synthesis of azetidine-derived natural products by the opportunistic pathogen Pseudomonas aeruginosa is controlled by quorum sensing, a process involving the production and sensing of diffusible signal molecules that is decisive for virulence regulation. In this study, we engineered P. aeruginosa for the titratable expression of the biosynthetic aze gene cluster, which allowed the purification and identification of two new products, azetidomonamide C and diazetidomonapyridone. Diazetidomonapyridone was shown to have a highly unusual structure with two azetidine rings and an open-chain diimide moiety. Expression of aze genes strongly increased biofilm formation and production of phenazine and alkyl quinolone virulence factors. Further physiological studies revealed that all effects were mainly mediated by azetidomonamide A and diazetidomonapyridone, whereas azetidomonamides B and C had little or no phenotypic impact. The P450 monooxygenase AzeF which catalyzes a challenging, stereoselective hydroxylation of the azetidine ring converting azetidomonamide C into azetidomonamide A is therefore crucial for biological activity. Based on our findings, we propose this group of metabolites to constitute a new class of diffusible regulatory molecules with community-related effects in P. aeruginosa.

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Section: ■ Conclusion and Outlookmentioning

confidence: 99%

Azetidomonamide and Diazetidomonapyridone Metabolites Control Biofilm Formation and Pigment Synthesis in Pseudomonas aeruginosa

et al. 2022

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Metabolomics and in-vitro bioactivities studies of fermented Musa paradisiaca pulp: A potential alpha-amylase inhibitor

Atunnise,

Bodede,

Adewuyi

et al. 2024

Heliyon

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Synthesis of Pyrrolizinone and Pyrrolizino[1,2-a]pyrrolizin-5-one Skeletons Starting From Pyrrole through a Single-Step and Catalyst-Free Approach

Amudi

Kuzu

Kolak

et al. 2023

Synlett

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1H-Pyrrole and lactone-type 2,3-furandione derivatives were reacted in anhydrous diethyl ether (Et2O) at room temperature, and then one of the important alkaloid skeletons, pyrrolizinone derivatives, were synthesized via a single step and catalyst-free approach. Various pyrrolizinone derivatives having various substituents such as phenyl, substituted phenyl, thiophene, -CF3, naphthalene, bi-phenyl, ester, and oxalate were yielded. Employing an equimolar pyrrole molecule yielded pyrrolizinones, while using an excess molar of pyrrole yielded pyrrolizino[1,2-a]pyrrolizin-5-one which is not present in the literature. Yield of purified molecules was up to 91%. One of the cyclization processes was carried out on a gram-scale, yielding 0.952 g (71%).

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Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

Cited by 5 publications

References 41 publications

Azetidomonamide and Diazetidomonapyridone Metabolites Control Biofilm Formation and Pigment Synthesis in Pseudomonas aeruginosa

Azetidomonamide and Diazetidomonapyridone Metabolites Control Biofilm Formation and Pigment Synthesis in Pseudomonas aeruginosa

Metabolomics and in-vitro bioactivities studies of fermented Musa paradisiaca pulp: A potential alpha-amylase inhibitor

Synthesis of Pyrrolizinone and Pyrrolizino[1,2-a]pyrrolizin-5-one Skeletons Starting From Pyrrole through a Single-Step and Catalyst-Free Approach

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