Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Divergent Synthesis of Quinolone Natural Products from Pseudonocardia sp. CL38489.

ABSTRACT: Two divergent synthetic routes are reported offering access to four quinolone natural products from Pseudonocardia sp. CL38489. Key steps to the natural products involved a regioselective epoxidation, an intramolecular Buchwald-Hartwig amination and a final acid-catalysed 1,3-allylic-alcohol rearrangement to give two of the natural products in one step. This study completes the synthesis of all eight antibacterial quinolone natural products reported in the family. In addition, this modular strategy enables an improved synthesis towards two natural products previously reported.

SUBMITTER: Geddis SM

PROVIDER: S-EPMC5215369 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Divergent Synthesis of Quinolone Natural Products from Pseudonocardia sp. CL38489.

Geddis Stephen M SM Carro Laura L Hodgkinson James T JT Spring David R DR

European journal of organic chemistry 20161115 35

Two divergent synthetic routes are reported offering access to four quinolone natural products from Pseudonocardia sp. CL38489. Key steps to the natural products involved a regioselective epoxidation, an intramolecular Buchwald-Hartwig amination and a final acid-catalysed 1,3-allylic-alcohol rearrangement to give two of the natural products in one step. This study completes the synthesis of all eight antibacterial quinolone natural products reported in the family. In addition, this modula ...[more]

PMID: 28111524

Similar Datasets

The Synthesis of Quinolone Natural Products from Pseudonocardia sp.

Project description:Abstract The synthesis of four quinolone natural products from the actinomycete Pseudonocardia sp. is reported. The key step involved a sp2–sp3 Suzuki–Miyaura reaction between a common boronic ester lateral chain and various functionalised quinolone cores. The quinolones slowed growth of E. coli and S. aureus by inducing extended lag phases.

| S-EPMC4744947 | biostudies-literature

Synthesis and biological evaluation of 1,2-disubsubstituted 4-quinolone analogues of Pseudonocardia sp. natural products.

Project description:A series of analogues of Pseudonocardia sp. natural products were synthesized, which have been reported to possess potent antibacterial activity against Helicobacter pylori and induce growth defects in Escherichia coli and Staphylococcus aureus. Taking inspiration from a methodology used in our total synthesis of natural products, we applied this methodology to access analogues possessing bulky N-substituents, traditionally considered to be challenging scaffolds. Screening of the library provided valuable insights into the structure-activity relationship of the bacterial growth defects, and suggested that selectivity between bacterial species should be attainable. Furthermore, a structurally related series of analogues was observed to inhibit production of the virulence factor pyocyanin in the human pathogen Pseudomonas aeruginosa, which may be a result of their similarity to the Pseudomonas quinolone signal (PQS) quorum sensing autoinducer. This provided new insights regarding the effect of N-substitution in PQS analogues, which has been hitherto underexplored.

| S-EPMC6204808 | biostudies-literature

Bioactive natural products from Pseudonocardia endophytica VUK-10.

Project description:Two proline containing cyclic dipeptides (CDPs), cyclo (L-Pro-L-Tyr) (1) and cyclo (L-Pro-L-Phe) (2) were isolated from the fermentation broth of Pseudonocardia endophytica VUK-10 originating from the Nizampatnam mangrove ecosystem on the south coast of Andhra Pradesh, India. The structures of the compounds were established by 1H NMR and 13C NMR spectroscopy, FTIR and EIMS. The antimicrobial and cytotoxic activities of the compounds were tested against a variety of medicinally and agriculturally important bacteria and fungi as well as on the MDA-MB-231, OAW-42, HeLa and MCF-7 human cell lines. Xanthomonas malvacearum was most sensitive toward 1 (MIC 4 ?g/ml), whereas compound 2 had good antibacterial activity against Xanthomonas campestris (MIC 8 ?g/ml). Fusarium solani was highly sensitive toward 1 (MIC 16 ?g/ml). The compounds were cytotoxic against the human cell lines at micro molar concentrations; the highest activity (IC50 < 10 ?M) of 1 was recorded against the MDA-MB-231 cancer cell line.

| S-EPMC6299850 | biostudies-other

A divergent strategy for the synthesis of secologanin derived natural products.

Project description:The syntheses of D,L-geissoschizol, D,L-corynantheidol, D,L-dihydrocorynantheol, D,L-protoemetinol, and D,L-3-epi-protoemetinol have been accomplished from a single synthetic intermediate.

| S-EPMC3037978 | biostudies-literature

Engineered Biosynthesis of Fungal 4-Quinolone Natural Products.

Project description:Quinolone-containing natural products are widely found in bacteria, fungi, and plants. The fungal quinolactacins, which are N-methyl-4-quinolones, display a wide spectrum of biological activities. Here we uncovered a concise nonribosomal peptide synthetase pathway involved in quinolactacin A biosynthesis from Penicillium by using heterologous reconstitution and in vitro enzymatic synthesis. The N-desmethyl analog of quinolactacin A was accessed through the construction of a hybrid bacterial and fungi pathway in the heterologous host.

| S-EPMC8110742 | biostudies-literature

Synthesis of several cleistrioside and cleistetroside natural products via a divergent de novo asymmetric approach.

Project description:The de novo asymmetric syntheses of several partially acylated dodecanyl tri- and tetra-rhamnoside natural products (cleistriosides-5 and 6 and cleistetrosides-2 to 7) have been achieved (19-24 steps). The divergent route requires the use of three or less protecting groups. The asymmetry was derived via Noyori reduction of an acylfuran. The rhamno-stereochemistry was installed by a diastereoselective palladium-catalyzed glycosylation, ketone reduction and dihydroxylation.

| S-EPMC3059258 | biostudies-literature

Divergent pathways in the biosynthesis of bisindole natural products.

Project description:Two molecules of the amino acid L-tryptophan are the biosynthetic precursors to a class of natural products named the "bisindoles." Hundreds of these bisindole molecules have been isolated from natural sources, and many of these molecules have potent medicinal properties. Recent studies have clarified the biosynthetic construction of six bisindole molecules, revealing novel enzymatic mechanisms and leading to combinatorial synthesis of new bisindole compounds. Collectively, these results provide a vantage point for understanding how much of the diversity of the bisindole class is generated from a small number of diverging pathways from L-tryptophan, as well as enabling identification of bisindoles that are likely derived via completely distinct biosynthetic pathways.

| S-EPMC2711870 | biostudies-literature

Divergent approach to the bisanthraquinone natural products: total synthesis of (S)-bisoranjidiol and derivatives from binaphtho-para-quinones.

Project description:The development of the first asymmetric synthesis of a chiral anthraquinone dimer is outlined, resulting in the first total synthesis of (S)-bisoranjidiol. Rather than a biomimetic dimerization retrosynthetic disconnection, the anthracenyl ring systems are generated after formation of the axially chiral binaphthalene framework. This synthetic strategy has enabled the synthesis of several analogues. Key features of the synthesis include the enantioselective coupling of a hindered 2-naphthol containing substitution peri to the site of C-C bond formation, the regioselective oxidation of 8,8'-hydroxylated binaphthols to binaphtho-para-quinones, and a tandem regioselective Diels-Alder/aromatization reaction.

| S-EPMC3560291 | biostudies-literature

Stereodivergent, Chemoenzymatic Synthesis of Azaphilone Natural Products.

Project description:Selective access to a targeted isomer is often critical in the synthesis of biologically active molecules. Whereas small-molecule reagents and catalysts often act with anticipated site- and stereoselectivity, this predictability does not extend to enzymes. Further, the lack of access to catalysts that provide complementary selectivity creates a challenge in the application of biocatalysis in synthesis. Here, we report an approach for accessing biocatalysts with complementary selectivity that is orthogonal to protein engineering. Through the use of a sequence similarity network (SSN), a number of sequences were selected, and the corresponding biocatalysts were evaluated for reactivity and selectivity. With a number of biocatalysts identified that operate with complementary site- and stereoselectivity, these catalysts were employed in the stereodivergent, chemoenzymatic synthesis of azaphilone natural products. Specifically, the first syntheses of trichoflectin, deflectin-1a, and lunatoic acid A were achieved. In addition, chemoenzymatic syntheses of these azaphilones supplied enantioenriched material for reassignment of the absolute configuration of trichoflectin and deflectin-1a based on optical rotation, CD spectra, and X-ray crystallography.

| S-EPMC7029798 | biostudies-literature

Biodegradation of ether pollutants by Pseudonocardia sp. strain ENV478.

Project description:A bacterium designated Pseudonocardia sp. strain ENV478 was isolated by enrichment culturing on tetrahydrofuran (THF) and was screened to determine its ability to degrade a range of ether pollutants. After growth on THF, strain ENV478 degraded THF (63 mg/h/g total suspended solids [TSS]), 1,4-dioxane (21 mg/h/g TSS), 1,3-dioxolane (19 mg/h/g TSS), bis-2-chloroethylether (BCEE) (12 mg/h/g TSS), and methyl tert-butyl ether (MTBE) (9.1 mg/h/g TSS). Although the highest rates of 1,4-dioxane degradation occurred after growth on THF, strain ENV478 also degraded 1,4-dioxane after growth on sucrose, lactate, yeast extract, 2-propanol, and propane, indicating that there was some level of constitutive degradative activity. The BCEE degradation rates were about threefold higher after growth on propane (32 mg/h/g TSS) than after growth on THF, and MTBE degradation resulted in accumulation of tert-butyl alcohol. Degradation of 1,4-dioxane resulted in accumulation of 2-hydroxyethoxyacetic acid (2HEAA). Despite its inability to grow on 1,4-dioxane, strain ENV478 degraded this compound for > 80 days in aquifer microcosms. Our results suggest that the inability of strain ENV478 and possibly other THF-degrading bacteria to grow on 1,4-dioxane is related to their inability to efficiently metabolize the 1,4-dioxane degradation product 2HEAA but that strain ENV478 may nonetheless be useful as a biocatalyst for remediating 1,4-dioxane-contaminated aquifers.

| S-EPMC1538739 | biostudies-literature