Iromycins: a new family of pyridone metabolites from Streptomyces sp. II. Convergent total synthesis

The total synthesis of iromycin A (1a), a microbial metabolite combining a novel structure with an interesting biological activity as a NO synthase inhibitor, was accomplished using a flexible and highly convergent approach. Thus, the ring fragment was prepared as 6-bromomethylpyrone 27 by acylation of the respective beta-ketoester 13 and subsequent lactonization of the thus-obtained beta,delta-diketoester 11, followed by bromination of the 6-methyl group. In addition, the unsaturated side chain was efficiently prepared as terminal alkyne 34 which was then carboaluminated to furnish the alkenyldimethylalane 35. The assembly of these two fragments was thoroughly studied using nickel, palladium, and copper catalysts yet only succeeded in the absence of any transition metal after formation of the respective lithium alkenyltrialkylalanate. Treatment of the coupled product 41 with liquid ammonia then completed the total synthesis which furnished an 18% overall yield over the nine steps of the longest linear sequence.     

Antimicrobial activity of secondary metabolites from Streptomyces sp. K15, an endophyte in Houttuynia cordata Thunb

We isolated Streptomyces sp. K15 from the root tissue of Houttuynia cordata Thunb and found that some of its secondary metabolites exhibited significant antimicrobial activity against Botrytis cinerea. Moreover, we separated, purified and identified the major active ingredient to be 2-pyrrol formic acid by using silica gel column chromatography, high-performance liquid chromatography and NMR analysis of the spectral data. 2-Pyrrol formic acid critically inhibited the growth of some phytopathogenic bacteria. Therefore, it has potential value in agricultural applications.     

A new isobenzofuranone derivative from a marine Streptomyces sp.

One new isobenzofuranone derivative,1,4-dimethoxy-3-(3R*-hydroxy-3R*-methyl-1-tetralone)-1(3H)-isobenzofuran(1),was isolated from the broth of marine Streptomyces sp.M268.The structure was elucidated by spectroscopy characteristics as well as comparison with the literature.Compound 1 exhibited cytotoxicities against human cancer cell,HL-60,A549,and BEL-7402.     

Izumiphenazine D, a new phenazoquinoline N-oxide from Streptomyces sp. IFM 11204

A new phenazine derivative named izumiphenazine D (1), together with three known metabolites, 1-hydroxyphenazine (2), phenazine-1-carboxylic acid (3) and 6-hydroxyphenazine-1-carboxylic acid (4) has been isolated from the ethyl acetate extract of culture of Streptomyces sp. IFM 11204. The structure of 1 was established via spectroscopic methods, including 1D- and 2D-NMR measurements.     

Isostreptazolin and sannaphenol, two new metabolites from Streptomyces sannanensis

Two new compounds, isostreptazolin (1) and sannaphenol (2), were isolated from the culture broth of Streptomyces sannanensis and their structures elucidated on the basis of 1D and 2D NMR as well as MS, IR and UV spectroscopic data analysis. The cytotoxic activity of 1 and 2 were evaluated. Both compounds were inactive against H460 and HeLa cell lines at 100 mM.     

Neaumycin: a new macrolide from Streptomyces sp. NEAU-x211

Neaumycin, a new 30-membered macrolide featuring an internal diester bridge, a molecular architecture that is unprecedented among known macrolide natural products, was isolated from a soil actinomycete strain Streptomyces sp. NEAU-x211. The structure of neaumycin was elucidated on the basis of comprehensive mass and NMR spectroscopic interpretation, including the relative stereochemistry of four independent coupling systems.     

Cytotoxic gephyromycins from the Streptomyces sp. SS13I

Two new gephyromycins (1–2), belonging to angucyclinones, were identified from Streptomyces sp. SS13I. Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and the structure of 1 was further elucidated by X-ray diffraction data. The absolute configurations of compounds 1–2 were evidenced by ECD calculations. To our best knowledge, Compounds 1–2 were the second reported gephyromycin-type angucyclinones. Compound 2 exhibited significant cytotoxicity against PC3 cell lines with IC₅₀ values of 1.38 ± 0.47 μM.     

Sesquiterpenes from the secondary metabolites of Streptomyces sp. (YIM 56130)

Three new sesquiterpenes were isolated from the fermentation broth of Streptomyces sp. and their structures were determined as caryolane-1,7α-diol (1), 1,6,11-eudesmanetriol; (1α,6β)-form (2), 11-eudesmene-1,6-diol; (1α,6β)-form (3), together with nine known compounds as caryolane-1,9α-diol (4), 2-methyl-5-nonanol (5), soyasaponin I (6), cyclo (Ala-Leu) (7), homononatinic acid (8), β-sitosteryl glucoside-3'-O-heptadecoicate (9), 2'-deoxythymidine (10), 2'-deoxyuridine (11), trehalose (12). The structures were elucidated by spectral analysis.     

One new anthraquinone from marine Streptomyces sp. FX-58

One new anthraquinone, 1,8-dihydroxy-2-ethyl-3-methylanthraquinone (1), together with two known compounds octadecanoic acid (2) and cholest-4-en-3-one (3) was isolated from marine actinomycete Streptomyces sp. FX-58. The structure of 1 was elucidated on the basis of spectroscopic methods, especially, the 2D-NMR spectral analysis. The cytotoxic activities of 1 were evaluated in vitro.     

Structure,biosynthetic origin,and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor

The calcium-dependent antibiotic (CDA), from Streptomyces coelicolor, is an acidic lipopeptide comprising an N-terminal 2,3-epoxyhexanoyl fatty acid side chain and several nonproteinogenic amino acid residues. S. coelicolor grown on solid media was shown to produce several previously uncharacterized peptides with C-terminal Z-dehydrotryptophan residues. The CDA biosynthetic gene cluster contains open reading frames encoding nonribosomal peptide synthetases, fatty acid synthases, and enzymes involved in precursor supply and tailoring of the nascent peptide. On the basis of protein sequence similarity and chemical reasoning, the biosynthesis of CDA is rationalized. Deletion of SCO3229 (hmaS), a putative 4-hydroxymandelic acid synthase-encoding gene, abolishes CDA production. The exogenous supply of 4-hydroxymandelate, 4-hydroxyphenylglyoxylate, or 4-hydroxyphenylglycine re-establishes CDA production by the DeltahmaS mutant. Feeding analogs of these precursors to the mutant resulted in the directed biosynthesis of novel lipopeptides with modified arylglycine residues.     

Antimicrobial and antioxidant activities of a new benzamide from endophytic Streptomyces sp. YIM 67086

A new benzamide (1) and four known compounds (2–5) were isolated from endophytic Streptomyces YIM67086, and their structures were determined as 2-amino-3,4-dihydroxy-5-methoxybenzamide (1), 4-hydroxy-3-methoxybenzoic acid (2), phenylacetic acid (3), N-acetyltyramine (4) and p-hydroxytruxinic acid (5). Compound 5 was first found in the microorganism. The antimicrobial activities of compounds 1–5 and antioxidant activity of compound 1 were investigated.     

Acetylcholinesterase inhibitory active metabolites from the endophytic fungus Colletotrichum sp. YMF432

An endophytic fungus, Chaetomium sp. YMF432, was isolated from Huperzia serrata (Thunb. ex Murray) Trev. and subjected to phytochemical investigation based on its special environment. From the extracts of fermentation solid of strain YMF 432, eight compounds including 1-O-methylemodin (1), 5-methoxy-2-methyl-3-tricosyl-1,4-benzoquinone (2), 4,8-dihydroxy-1-tetralone (3), (3β,5α,6α, 22E)-3-hydroxy-5,6-epoxy-7-one-8(14),22-dien-ergosta (4), ergosta-4,6,8(14),22-tetraen-3-one (5), β-sitostenone (6), β-sitosterol (7) and (22E,24R)-ergosta-5,7,22 -trien-3β-ol (8) were obtained. Their structures were elucidated on the basis of their spectroscopic data. These compounds were evaluated for acetylcholinesterase inhibitory activities in vitro. Compounds 1, 2, and 4 showed moderate acetylcholinesterase inhibitory activities (IC₅₀ from 37.7 ± 1.5 to 370.0 ± 2.9 μM).     

Four new anthraquinones from a soil actinomycete Streptomyces sp. WS-13394 and their bioactivities

Further chemical study of secondary metabolites from the soil actinomycete Streptomyces sp. WS-13394 resulted in the isolation of four new alkylated anthraquinone analogues (5–8). Their structures were elucidated on the basis of extensive spectroscopic analysis, including HR-ESI-MS, 1D and 2D NMR. The new compounds, together with analogues obtained before (1–4), were tested for their in vitro cytotoxicity against Huh-7 and SGC-7901.     

Structure of ulososide A,a new triterpenoid glycoside from theUlosa sp. sponge

A new triterpenoid glycoside, (20S,22S,23R,24S)-3,22,23-trihydroxy-3-O-[O-(-D-glucuronopyranosyl)-(16)-(-D-glucopyranosyl)]-14-nor-24-methyllanost-8(9)-en-31-oic acid (ulososide A), has been isolated from the sponge Ulosa sp. and characterized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1326–1329, July, 1994.     

Comprehensive study of okaspirodiol: characterization, total synthesis, and biosynthesis of a new metabolite from Streptomyces

The new spiro[4.5]acetal okaspirodiol (4) was isolated from Streptomyces sp. G? TS 19 as a secondary metabolite in yields up to 380 mg/L. The structure of this cryptic ketotetrol was elucidated by different methods including X-ray analysis, and its equilibration under mildly acidic conditions furnishing three additional isomers was thoroughly studied. Although metabolite 4 is not the thermodynamically favored isomer, a high-yielding total synthesis was accomplished comprising a stereoselective spiroacetalization under equilibrium conditions. This approach benefits from the important influence of an intramolecular hydrogen bond on the stabilization of the spiro[4.5]acetal moiety. The biosynthesis of 4 was investigated by feeding experiments with 13C-labeled precursors proving its origin from a new type of the rare mixed acetate-glycerol biosynthetic pathway. All results are discussed on the basis of the structural diversity of spiroacetals in nature and their chemical properties.     

Structure and biosynthesis of amychelin, an unusual mixed-ligand siderophore from Amycolatopsis sp. AA4

Actinobacteria generate a large number of structurally diverse small molecules with potential therapeutic value. Genomic analyses of this productive group of bacteria show that their genetic potential to manufacture small molecules exceeds their observed ability by roughly an order of magnitude, and this revelation has prompted a number of studies to identify members of the unknown majority. As a potential window into this cryptic secondary metabolome, pairwise assays for developmental interactions within a set of 20 sequenced actinomycetes were carried out. These assays revealed that Amycolatopsis sp. AA4, a so-called "rare" actinomycete, produces a novel siderophore, amychelin, which alters the developmental processes of several neighboring streptomycetes. Using this phenotype as an assay, we isolated amychelin and solved its structure by NMR and MS methods coupled with an X-ray crystallographic analysis of its Fe-complex. The iron binding affinity of amychelin was determined using EDTA competition assays, and a biosynthetic cluster was identified and annotated to provide a tentative biosynthetic scheme for amychelin.     

Diazonamides C-E, new cytotoxic metabolites from the ascidian Diazona sp.

Three new macrocyclic peptides, diazonamides C-E (1-3), were isolated together with the previously reported diazonamides A (4) and B (5) from samples of the marine ascidian Diazona sp. collected in Indonesia. Their structures were assigned on the basis of detailed analysis of the 1D and 2D NMR and mass spectral data as well as Marfey’s analysis of the aminoacid residues. All the new compounds isolated displayed moderate cytotoxicity against a panel of three human tumor cell lines.     

Absolute structure, biosynthesis, and anti-microtubule activity of phomopsidin, isolated from a marine-derived fungus Phomopsis sp.

The absolute configuration of phomopsidin, a marine-derived fungal metabolite from Phomopsis sp. isolated at Pohnpei, was determined by the exciton chirality method as 6S, 7S, 8S, 11S, 12R, and 15R. The biosynthetic study using ¹³C-labeled precursors revealed the origin of all carbon atoms in phomopsidin, which was built by nine acetates and three methyl groups from l-methionine. Inhibitory activities of phomopsidin and its Me ester derivative against microtubule assembly were examined together with the structurally related compounds MK8383, solanapyrones, and tanzawaic acids. Phomopsidin and its (16Z)-isomer (MK8383) showed anti-microtubule activity at IC₅₀ of 5.7 and 8.0 μM, respectively, while the Me ester and other compounds were not active at 100 μM.     

Akanthomycin, a new antibiotic pyridone from the entomopathogenic fungus Akanthomyces gracilis

[structure: see text] Organic extracts of the entomopathogenic fungus Akanthomyces gracilis ARS 2910 contained antibiotics active against Staphylococcus aureus. Bioassay-guided fractionation of the CH2Cl2 extract yielded the antibacterial compound akanthomycin as a mixture of atropisomers along with the closely related compounds 8-methylpyridoxatin and cordypyridone C. Akanthomycin was characterized using X-ray crystallography and NMR.