Complete Stereochemical Assignment of Campechic Acids A and B

Campechic acids A and B are anti-invasive polyketide antibiotics isolated from Streptomyces sp. CHI93 strain. Herein we describe stereoselective synthesis of the C-16–C-30 fragment of campechic acids A and B via a biosynthesis-inspired epoxide-opening cascade and its NMR spectroscopic comparison with the authentic degradation product, resulting in configurational assignment of the C-21, C-24, C-25, and C-28 stereogenic centers and reassignment of the C-18 stereogenic center

Species-level assessment of secondary metabolite diversity among <i>Hamigera</i> species and a taxonomic note on the genus

<div><p>Secondary metabolite phenotypes in nine species of the <i>Hamigera</i> clade were analysed to assess their correlations to a multi-gene species-level phylogeny. High-pressure-liquid-chromatography-based chemical analysis revealed three distinctive patterns of secondary metabolite production: (1) the nine species could be divided into two groups on the basis of production of the sesquiterpene tricinonoic acid; (2) the tricinonoic acid-producing group produced two cyclic peptides avellanins A and B; (3) the tricinonoic acid-non-producing group could be further divided into two groups according to the production of avellanins A and B. The chemical phenotype was consistent with the phylogeny of the species, although metabolite patterns were not diagnostic at the species level. In addition, the taxonomy of the <i>Hamigera</i> clade was updated with the new combination <i>Hamigera ingelheimensis</i> proposed for <i>Merimbla ingelheimensis</i>, so that all species in the clade are now in the same genus.</p></div

Biosynthetic Origin of Alchivemycin A, a New Polyketide from <i>Streptomyces</i> and Absolute Configuration of Alchivemycin B

Biosynthetic origin of 2<i>H</i>-tetrahydro-4,6-dioxo-1,2-oxazine, an unprecedented structural unit first discovered in alchivemycin A (<b>1</b>), was investigated by feeding ¹³C-labeled precursors. Incorporations of both [1-¹³C]glycine and [1-¹³C]-<i>N</i>-hydroxyglycine into the carbon at the 4-position of this six-membered ring indicate that the hydrooxazine ring is assembled through a PKS-NRPS hybrid pathway. Additionally, alchivemycin B (<b>2</b>), a deoxygenated analog of <b>1</b>, was isolated and its relative and absolute configurations were determined by spectroscopic analysis including NMR and CD and X-ray crystallography

Campechic Acids A and B: Anti-invasive Polyether Polyketides from a Soil-Derived <i>Streptomyces</i>

Campechic acids A (<b>1</b>) and B (<b>2</b>), two new polyketides, were isolated from the culture extract of <i>Streptomyces</i> sp., and their structures were determined by NMR and MS spectroscopic analysis. Campechic acids are polyether-polyketides functionalized by two tetrahydrofuran rings, an enolized 1,3-diketone, and multiple methyl substitutions. Absolute configuration of nine stereogenic centers in <b>1</b>, except for four chiral centers in the cyclic ether moieties, was determined by the ¹H NMR anisotropy method in combination with chemical degradation. Campechic acids exhibited potent inhibitory effects on tumor cell invasion with IC₅₀ values in the nanomolar to submicromolar range

Akaeolide, a Carbocyclic Polyketide from Marine-Derived <i>Streptomyces</i>

Akaeolide, a novel polycyclic polyketide, was isolated from the culture extract of a marine-derived actinomycete belonging to the genus <i>Streptomyces</i>. The planar structure of the new compound was elucidated by spectroscopic analysis including NMR and MS, and the absolute configuration was determined by X-ray crystallographic analysis of its chlorinated derivative. Akaeolide possesses a 15-membered carbocyclic framework, apparently derived from the malonate pathway, with a tetrahydrofuran ring and a β-keto-δ-lactone unit

Ulbactins F and G, Polycyclic Thiazoline Derivatives with Tumor Cell Migration Inhibitory Activity from Brevibacillus sp.

Two new structurally unique compounds bearing a nitrogen- and sulfur-containing tricyclic ring system, ulbactin F (<b>1</b>) and its diastereomeric isomer ulbactin G (<b>2</b>), were isolated from the culture extract of a sponge-derived Brevibacillus sp. The structures and absolute configurations of <b>1</b> and <b>2</b> were determined by NMR analysis and X-ray crystallographic analysis. These compounds inhibit the migration of tumor cells in the submicromolar to micromolar range

Complete Stereochemistry and Preliminary Structure–Activity Relationship of Rakicidin A, a Hypoxia-Selective Cytotoxin from <i>Micromonospora</i> sp.

The complete stereochemistry of rakicidin A, a hypoxia-selective cytotoxin produced by <i>Micromonospora</i> sp., was unambiguously established by extensive chemical degradation and derivatization studies. During the PGME derivatization-based configurational analysis of 3-hydroxy-2,4,16-trimethylheptadecanoic acid, an irregular Δδ distribution was observed, which necessitated further acylation of the 3-hydroxy group to resolve the inconsistency. A hydrogenated derivative of rakicidin A, its ring-opened product, and two congeners with different alkyl chain lengths were tested for hypoxia-selective cytotoxicity. The results indicated that both the conjugated diene unit and appropriate chain length are essential for the unique activity of rakicidin A

Krasilnikolides A and B and Detalosylkrasilnikolide A, Cytotoxic 20-Membered Macrolides from the Genus <i>Krasilnikovia</i>: Assignment of Anomeric Configuration by <i>J</i>‑Based Configuration Analysis

A chemical investigation of strain RD003821, belonging to the underexplored actinomycetes genus Krasilnikovia, led to the discovery of three novel polyketides: two 20-membered glycomacrolides, krasilnikolides A (1) and B (2), and an aglycone of 1, detalosylkrasilnikolide A (3). A major challenge in the structure elucidation of 1 was to determine the anomeric configuration of the α-l-6-deoxytalose (6dTal) unit, which was achieved by J-based configuration analysis (JBCA) that incorporated anomeric carbon- and proton-specific two-bond 13C–1H spin–spin coupling constants as diagnostic parameters. The updated criteria for the conformation/configuration assignment facilitated discrimination of three out of four stereochemical variants at the anomeric and the adjacent C2 positions, which expanded the scope of the JBCA method to determination of the anomeric configuration of aldohexopyranoses. Compounds 1 and 2 are the first macrolides decorated by 6dTal. Compounds 1–3 exhibited cytotoxicity against P388 murine leukemia cells with IC50 values of 14, 8.4, and 3.9 μM, respectively. In addition, 1–3 were antibacterial against the Gram-positive bacterium Kocuria rhizophila with MIC values of 25, 50, and 100 μg/mL. 1 was inhibitory against Staphylococcus aureus with an MIC of 50 μg/mL

Characterization and Carbohydrate Specificity of Pradimicin S

The pradimicin family of antibiotics is attracting attention due to its anti-infective properties and as a model for understanding the requirements for carbohydrate recognition by small molecules. Members of the pradimicin family are unique among natural products in their ability to bind sugars in a Ca²⁺-dependent manner, but the oligomerization to insoluble aggregates that occurs upon Ca²⁺ binding has prevented detailed characterization of their carbohydrate specificity and biologically relevant form. Here we take advantage of the water solubility of pradimicin S (PRM-S), a sulfated glucose-containing analogue of pradimicin A (PRM-A), to show by NMR spectroscopy and analytical ultracentrifugation that at biologically relevant concentrations, PRM-S binds Ca²⁺ to form a tetrameric species that selectively binds and engulfs the trisaccharide Manα1–3­(Manα1–6)­Man over mannose or mannobiose. In functional HIV-1 entry assays, IC₅₀ values of 2–4 μM for PRM-S corrrelate with the concentrations at which oligomerization occurs as well as the affinities with which PRM-S binds the HIV surface envelope glycoprotein gp120. Together these data reveal the biologically active form of PRM-S, provide an explanation for previous speculations that PRM-A may contain a second mannose binding site, and expand our understanding of the characteristics that can engender a small molecule with the ability to function as a carbohydrate receptor

Arthroamide, a Cyclic Depsipeptide with Quorum Sensing Inhibitory Activity from <i>Arthrobacter</i> sp.

Nonfilamentous actinobacteria have been less studied as secondary metabolite producers than their filamentous counterparts such as <i>Streptomyces</i>. From our collection of nonfilamentous actinobacteria isolated from sandstone, an <i>Arthrobacter</i> strain was found to produce a new cyclic peptide arthroamide (<b>1</b>) together with the known compound turnagainolide A (<b>2</b>). These compounds inhibited the quorum sensing signaling of <i>Staphylococcus aureus</i> in the submicromolar to micromolar range