Homononactic Acid Research Articles

Discovery of a Novel Chromone Enantiomer and the Precursors of Nonactic Acid from the Coral-Reef-Derived Streptomyces sp. SCSIO 66814.

Three pairs of enantiomers (1-3)-the new 12R-aloesol (1a) and two new fatty acids (2 and 3)-and one new natural product (4) together three known compounds (5-7) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 2-5, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals.

Secondary Metabolites with Cytotoxic Activities from Streptomyces sp. BM-8 Isolated from the Feces of Equusquagga

A new aliphatic acid, compound 1, together with six known metabolites, including nonactic acid (2), homononactic acid (3), ethyl homononactate (4), homononactylhomononactate (5), valinomycin (6), and cyclo-(Pro-Leu) (7), was isolated from the culture broth of Streptomyces sp. BM-8, an actinobacterial strain isolated from the feces of Equus quagga. The structures of these compounds were established by analyses of spectroscopic data, including 1D and 2D nuclear magnetic resonance spectra (NMR), as well as by HR-ESI-MS spectrometry and chemical derivative analyses. Additionally, a serial analogue of nonactic acid and homononacticacid (8–21) was synthesized. The cytotoxicity of 1–21 wastested against a panel of cancer cell lines, such as HT-29, MCF-7, A375 and K562, with MTT assay. In addition, the cytotoxicity tests revealed that 1 was less cytotoxic toward a panel of cancerous cells, as compared with valinomycin (6).

Nonactic Acid Derivatives Isolated From Streptomyces werraensis IFM12104 in a Screening Program for BMI1 Promoter Inhibitory Activity

Upon screening for compounds with B cell-specific Moloney murine leukemia virus region 1 (BMI1) promoter inhibitory activity, 3 nonactic acid derivatives (1-3) were isolated from Streptomyces werraensis IFM12104. Although spectral data of compound 1 were identical with those reported in literature for 4α-(3, 5-dihydroxy-heptyl)-3α-methyl-2-oxetanone (4), compound 1 was revealed to be homononactic acid by X-ray analysis. Compounds 2 and 3 were identified as bishomononactic acid and nonactic acid using spectral data. The 3 compounds 1 to 3 inhibited BMI1 promoter activities with IC50 values of 240, 160, and 180 μM, respectively.

New bioactive derivatives of nonactic acid from the marine Streptomyces griseus derived from the plant Salicornia sp.

Three new compounds, butyl homononactate (5), butyl nonactate (6), 8-actyl homononactic acid (7), along with four known compounds homononactic acids (1), nonactic acid (2), homononactyl nonactate (3), homononactyl homononactate (4) were isolated from the marine Streptomyces griseus RSH0407, derived from the plant Salicornia sp., Chenopodiaceae. Their structures were elucidated by extensive spectroscopic techniques and by comparison with data reported in the literature. The absolute configuration of 3 was first reported by using X-ray copper radiation. Compound 5 exhibited cytotoxic activities against the HCT-8, A2780, BGC-823, BEL-7402, and A549 cell lines in vitro, with IC50 values of 2.87±0.20, 4.90±0.30, 2.19±0.32, 5.07±0.23 and 1.78±0.18μM, respectively, and compounds 4–7 showed weak antibacterial activities against four bacterials respectively.

Bioactive Secondary Metabolites from Terrestrial Streptomyces baarnensis MH4

Aims: Isolation, screening and identification of potent bioactive compounds producing Streptomyces sp. from the terrestrial soil of Egypt. Fermentation study, product recovery, purification and its characterization was also taken into consideration. Study Design: Cultivation in lab fermenter, solvent extraction and purification of the compounds by column chromatography, identification of the compounds by mass spectrometry and NMR spectroscopy, determination of the antimicrobial activity. Place and Duration of Study: Institute of Organic and Biomolecular Chemistry, University of Gottingen, Germany; Department of Microbial Chemistry, National Research Centre, Egypt and Chemistry of Natural Compounds Department, National Research Centre, Egypt, between January, 2009 and December, 2010. Methodology: The strain was cultivated at 25-liter shaker culture and the fermented broth was filtered and the filtrate was extracted by XAD-16 resin and then by methanol-water, and the concentrated water residue was extracted by ethyl acetate followed by evaporation till dryness. The resultant crude extract was fractionated on silica gel and the components were purified by column chromatography (silica gel, Sephadex column and preparative TLC). The pure component was identified by mass spectrometry (ESI and HRESI-MS), NMR analysis (1H,13C NMR, and 2D NMR) and by comparison with reference data. The antimicrobial activity was determined by disc diffusion assay. Results: The morphological, biochemical and physiological characterization suggested that isolate MH4 belongs to the genus Streptomyces. Comparison the obtained data with literature data and showed 99% identity coverage towards Streptomyces baarnensis. The scale up fermentation of the isolate MH4 yielded eight known metabolites, nonactic acid (2), homononactic acid (3), 3-(3,3-Di-indolyl)propane-1,2-diol (4), turbomycin A (5), indolyl-3-acetic acid, indolyl-3-carbaldehyde, indolyl-3-carboxylic acid and 2'–deoxyadenosine. Structures of the isolated compounds were assigned by intensive studies of nuclear magnetic resonance (NMR) and mass spectrometry and comparison with corresponding literatures. The taxonomical characterization, fermentation, and biological activity of the Streptomyces baarnensis MH4 were investigated. Conclusion: The isolate Streptomyces baarnensis MH4 is a potent producer of several antibiotic compounds which can be exploited for their commercial production.

ChemInform Abstract: New Derivatives of Nonactic and Homononactic Acids from Bacillus pumilus Derived from Breynia fruticosa.

Abstractisolation, structure and cytotoxicity

New Derivatives of Nonactic and Homononactic Acids from Bacillus pumilus Derived from Breynia fruticosa

Six new nonactic and homononactic acid derivatives, ethyl homononactate (1), ethyl nonactate (2), homononactyl homononactate (6), ethyl homononactyl nonactate (7), ethyl homononactyl homononactate (8), and ethyl nonactyl nonactate (9), as well as four known compounds, homononactic acid (3), nonactic acid (4), homononactyl nonactate (5), and bishomononactic acid (10), were isolated from culture broth of Bacillus pumilus derived from Breynia fruticosa. The structures of new compounds were elucidated by spectroscopic analysis and chemical methods. The optical purities of 1-6 were determined by HPLC/MS after treatment with L-phenylalanine methyl ester. The dimeric compounds 5-9 showed weak cytotoxic activities against five human cancer cell lines (IC50 19-100 μg/ml).

Determination of ionophore antibiotics nactins produced by fecal Streptomyces from sheep

To investigate the correlation between fecal actinobacteria and host animals, Streptomyces was isolated from fresh faeces of healthy sheep and secondary metabolites were analyzed. The most frequently isolated strain S161 with antibiotic activity against bacteria and fungi were analyzed. The S161 showed the highest 99 % similarity to Streptomyces canus DSB17 based on the 16S rRNA gene sequence analysis. Metabolite analysis based on MS and NMR spectra showed that S161 produces nactins, cyclotetralactones derived from nonactic acid and homononactic acid as building units of ionophoretic character. Due to ionophores are antimicrobial compounds that are commonly fed to ruminant animals to improve feed efficiency, stable beneficial interactions between Streptomyces bacteria and vertebrates have been demonstrated.

Chemical constitutes from endophytic Streptomyces sp. W5 isolated from Trewia nudiflora L.

Strain W5 was isolated from stem of Trewia nudiflora L. and identified as a member of Streptomyces according to its 16S rDNA partial sequence. From extracts of fermentation medium of W5, a new γ-butyrolactone (1), together with nine known compounds [2-methyl-2,5-bornandiol (2), dimeric dinactin (3), (R)-2-((2R,5S)-tetrahydro-5-(2-oxopropyl)furan-2-yl)propanoic acid (4), 2-(5-(2-acetoxypropyl)-tetrahydrofuran-2-yl)propanoic acid (5/6), (±)-homononactic acid (7/8), (±)-nonactic acid (9/10)] was isolated. Their structures were elucidated on the basis of extensive spectroscopic data.

Stereoselective Synthesis of the Published Structure of Feigrisolide A. Structural Revision of Feigrisolides A and B

The total synthesis of the proposed structure of feigrisolide A is reported. Ethyl (S)-3-hydroxybutyrate was the chiral starting material. A Brown asymmetric allylation and an Evans aldol reaction were key steps of the synthesis. The NMR data of the synthetic product are different from those of the natural product. The published structure of feigrisolide A is therefore erroneous. A subsequent comparison of spectral data strongly suggests that feigrisolides A and B are identical with (-)-nonactic acid and (+)-homononactic acid, respectively.

Five new derivatives of nonactic and homo-nonactic acids from Streptomyces globisporus

In addition to the known compounds of the type of nonactic and homononactic acids and their lactones, dilactones and tetralactones, five new compounds, namely homononactyl-nonactoate, a dilactone consisting of nonactic and homononactic acids and three cyclic trimers with nonactic and homononactic acids, were isolated from a strain of Streptomyces globisporus. Their structures, including the absolute configurations of the hydroxyl and methyl groups, were determined by extensive spectroscopic techniques such as UV, IR, MS, 1D and 2D NMR.

Nonactin biosynthesis: the initial committed step is the condensation of acetate (malonate) and succinate.

Nonactin is a macrotetrolide antibiotic produced by Streptomyces griseus subsp. griseus ETH A7796 that has shown activity against the P170-glycoprotein efflux pump associated with multiple drug resistant cancer cells. Nonactin is a polyketide, albeit a highly atypical one. The structure is composed of two units of each of the enantiomers of nonactic acid, arranged in a macrocycle, so that the molecule has S4 symmetry and is achiral. The monomer units, (+)- and (-)-nonactic acid, are derived from acetate, succinate, and propionate, although the exact details of the assembly process are quite unclear. We have used feeding experiments with a series of multiple stable isotope labeled precursors to elucidate the details of the first committed step of nonactic acid biosynthesis. We have found that the (13)C label from 3-ketoadipate is incorporated specifically into both nonactic acid and its homologue, homononactic acid. The data conclusively show that the first committed step of nonactin biosynthesis is the coupling of a succinate derivative with either acetate or malonate. The differentiation into either nonactate or homononactate occurs after the initial condensation; the homologues are not derived from use of a different "starter unit" by the nonactate polyketide synthase. The first step of nonactin biosynthesis involves achiral intermediates; differentiation between the known enantiocomplementary biosynthesis pathways to form each enantiomer of the precursor monomer units likely occurs after the initial condensation reaction.

Antifungal Actinomycete Metabolites Discovered in a Differential Cell-Based Screening Using a Recombinant TOPO1 Deletion Mutant Strain

In the course of a natural product screening for inhibitors of fungal topoisomerase 1 (TOPO 1), extracts from the actinomycete strains WS 1410 and BS 1465 exhibited promising activities. Bioguided fractionation of the culture broth by preparative HPLC methods yielded the collismycins A (1) and B (2) as active principles of strain WS 1410. Out of the mycelial extracts of strain BS 1465 the bioactive new natural products, cyclo-homononactic acid (3) and cyclo-nonactic acid (5) and the structurally related but inactive homononactic acid (4), were isolated. Both collismycin isomers inhibited the recombinant yeast strains ScAL 141 and ScAL 143 (TOPO 1 deletion mutant) in a non-specific manner with an MIC in the range of 2 micrograms/ml. The novel cyclo-homononactic acid (3) and cyclo-nonactic acid (5) showed higher selectivity towards the wild type strain (MIC = 2 micrograms/ml as compared to 10 micrograms/ml for the deletion mutant). All compounds obviously address a target other than TOPO 1 since they do not exhibit activities in a concurrent TOPO 1 enzyme assay.

ChemInform Abstract: Synthesis of (.+‐.)‐Homononactic Acid by Using cis‐Selective Iodoetherification.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of (±)-Homononactic Acid by Using cis-Selective Iodoetherification

Synthesis of (±)-Homononactic Acid by Using cis-Selective Iodoetherification

Synthetic studies on development of a novel macrolide ionophore: Configurational requirement of 16-membered macrodiolide for binding ability

Twelve synthetic 16-membered macrodiolides were prepared from racemic homononactic acid. The compounds which have an anti-relationship between the ether linkage of THF and the adjacent methyl showed the cation-binding ability. Macrodiolide 12 exhibited the ion selectivity for Li +.

Isolation of nonactic acids fromStreptomyces griseus fermentation broth by thin-layer and high-performance liquid chromatography

Nonactic acid, homononactic acid and their 2-diastereoisomers were isolated by thin-layer chromatography on silica gel and by high-performance liquid chromatography on a reversed phase from the fermentation broth ofStreptomyces griseus, and identified by1H and13C NMR spectroscopy.

Insecticidal properties of nonactic acid and homononactic acid, the precursors of macrotetrolide antibiotics

(±)-Nonactic acid (1) and (±)-homononactic acid (2), the non-antibiotic precursors of macrotetrolide antibiotics, showed significant insecticidal effects (comparable with those of the commercial synthetic pesticide Metathion) onLeptinotarsa decemlineata, Epilachna varivestis andEuproctis chrysorrhoea. Anisoplia austriaca, Aphis fabae andCalandra granaria were less sensitive in this respect. A low acaricidal activity againstTetranychus urticae (not reaching that of the commercial miticide Acarition) was also found. Both1 and2 exhibited growth-stimulating properties for plants.

ChemInform Abstract: Stereoselective Syntheses of the Nonactate Esters via Intramolecular Oxymercurations of Allenes.

AbstractNonactic acids are subunits of nactin antibiotics.

Stereoselective syntheses of the nonactate esters via intramolecular oxymercurations of allenes

The nactin antibiotic subunits (±)-nonactic acid, (±)-homononactic acid, and (±)-bishomononactic acid were synthesized as their methyl esters (14,15,16) by a route which forms the cis-2,5-disubstituted tetrahydrofuran ring moiety by a one-pot oxymercuration-transmetalation (with palladium)-methoxycarbonylation, which converts the γ-silyloxy allenes to the 2(10)- or 2(11)-dehydrononactate methyl esters with excellent cis:trans stereoselectivity