Total Synthesis and Biological Activity of (±)-Guignardin A, (±)-Palmarumycin B₉, and Their Derivatives

A strategy for constructing an α-hydroxyl-α-acetonyl moiety was described for the total synthesis of guignardin A (1), 8-deoxypalmarumycin B9 (2), and palmarumycin B9 (3) via 7-, 8-, and 11-step reactions in 14.9, 1.5, and 0.4% overall yields from 5-methoxy-1-tetralone (1a), chroman-4-one (2a), and 2,5-dimethoxybenzaldehyde (3a) as the starting materials, respectively. The key steps included AlCl3- or NaSEt-mediated demethylation, Davis oxidation, and Wacker oxidation. Their structures were characterized by 1H and 13C NMR, HR-ESI-MS, and X-ray diffraction data. A series of spiromamakone A monobenzo derivatives were designed and synthesized by three diallyl-substituted byproducts via olefin metathesis as the key step. The antifungal investigation indicated that compounds 1l and 2n exhibited excellent inhibitory activities against phytopathogen Rhizoctonia solani with EC50 values of 8.68 and 5.25 μg/mL, respectively. Compound 2n had the destructive and inhibitory effects on the morphology and growth of the hyphae of R. solani

Rosellosides A and B, two phenyloxazole glycosides from <i>Glycyrrhiza inflata</i>-derived fungus <i>Rosellinia</i> sp. Glinf021

Two new chlorinated phenyloxazole glycosides, named rosellosides A (1) and B (2), were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata (Leguminosae). Both compounds were rare chlorinated polyketide glycosides bearing an oxazole moiety. Their structures were elucidated by analysis of the NMR and HRESIMS data, and their absolute configurations were determined by quantum chemical ECD calculations and X-ray crystallography.</p

A new proline-containing flavonol glycoside from <i>Caragana leucophloea</i> Pojark

<div><p>One new proline-containing flavonol glycoside, namely kaempferol-3-<i>O</i>-methyl-7-<i>O</i>-β-d-glucopyranosyl-8-(1-methyleneproline)-4′-<i>O</i>-β-d-glucopyranoside (<b>1</b>), together with 15 known flavonoids, 3-<i>O</i>-methylkaempferol (<b>2</b>), 3-<i>O</i>-methylquercetin (<b>3</b>), quercetin (<b>4</b>), kaempferol (<b>5</b>), apigenin (<b>6</b>), rhamnazin (<b>7</b>), astragalin (<b>8</b>), alquds (<b>9</b>), quercitrin (<b>10</b>), rutin (<b>11</b>), isoquercitrin (<b>12</b>), apigetrin (<b>13</b>), myricitrin (<b>14</b>), hesperidin (<b>15</b>) and calycosin-7-<i>O</i>-β-d-glucopyranoside (<b>16</b>) were isolated from the aerial parts of <i>Caragana leucophloea</i> Pojark. (Leguminosae). Their structures were determined on the basis of spectroscopic analyses and by comparison with literature data. Compounds <b>2</b>–<b>4</b> revealed a strong antimicrobial activity with minimum inhibitory concentration values of 12.5–150 μg/mL and median inhibitory concentration (IC₅₀) values of 7.42–76.61 μg/mL. Compounds <b>3</b>, <b>4</b>, <b>6</b>–<b>8</b>, <b>10</b>–<b>12</b> and <b>14</b> showed strong antioxidant activity. Compounds <b>2</b>–<b>7</b> exhibited moderate antinematodal activity on <i>Caenorhabditis elegans</i> with IC₅₀ values of 40.51–68.05 μg/mL.</p></div

Dibenzo-α-pyrones from the endophytic fungus <i>Alternaria</i> sp. Samif01: isolation, structure elucidation, and their antibacterial and antioxidant activities

<p>The EtOAc extract of the liquid fermentation of <i>Alternaria</i> sp. Samif01, an endophytic fungus obtained from <i>Salvia miltiorrhiza</i> Bunge, showed antibacterial activity against several tested bacterial pathogens. Fractionation of this extract led to the isolation of seven dibenzo-α-pyrones (<b>1</b>–<b>7</b>), including one new compound, 2-acetoxy-2-<i>epi</i>-altenuene (<b>1</b>) and one new natural product, 3-<i>epi</i>-dihydroaltenuene A (<b>2</b>). The structures of the new metabolites were elucidated by comprehensive analysis of the spectroscopic data including (1D, 2D) NMR and HRESIMS, while the absolute configuration of <b>1</b> was determined by TDDFT–ECD computation. Altenuisol (<b>5</b>), 4-hydroxyalternariol-9-methyl ether (<b>6</b>), and alternariol (<b>7</b>) showed inhibitory activities against the tested bacteria with minimum inhibitory concentration values in the range of 86.7–364.7 μM. A preliminary structure–antibacterial activity relationship was discussed. In addition, compounds <b>2</b>, <b>5</b> and <b>6</b> displayed promising antioxidant effects using DPPH and hydroxyl radical assays. The cytotoxicity of the isolated compounds was evaluated as well.</p> <p>The endophytic fungus <i>Alternaria</i> sp. Samif01 isolated from <i>Salvia miltiorrhiza</i> Bunge produced seven bioactive dibenzo-α-pyrones, including one new compound (<b>1</b>), whose absolute configuration was determined by ECD calculation.</p

New Ustilaginoidins from Rice False Smut Balls Caused by Villosiclava virens and Their Phytotoxic and Cytotoxic Activities

Ustilaginoidins are a class of bis-naphtho-γ-pyrones, typically produced by Villosiclava virens, the pathogen of the rice false smut (RFS), which has been one of the most destructive rice fungal diseases. Previously, we found that ustilaginoidins identified from the culture of V. virens on rice medium were less polar than those reported from the RFS balls in general. In this study, we reinvestigated the high-performance liquid chromatography with diode array detection and high-resolution mass spectrometry (HPLC–DAD–HRMS) profile of the ethyl acetate (EtOAc) extract of the RFS balls and found several interesting peaks that correspond to new ustilaginoidins. As a result, eight new and polar congeners, named ustilaginoidins Q–T (<b>1</b>–<b>4</b>), 2,3-dihydroustilaginoidin T (<b>5</b>), and ustilaginoidins U–W (<b>6</b>–<b>8</b>), were isolated. In addition, 17 known ustilaginoidins, including ustilaginoidins K–N (<b>9</b>–<b>12</b>), ustilaginoidin P (<b>13</b>), ustilaginoidin E₁ (<b>14</b>), isochaetochromin B₂ (<b>15</b>), and ustilaginoidins A–J (<b>16</b>–<b>25</b>), were re-isolated. The structures of the new compounds were elucidated by comprehensive analysis of the spectroscopic data. Ustilaginoidins Q (<b>1</b>) and R (<b>2</b>) feature an uncommon 2-hydroxypropyl-substituted skeleton and biogenetically incorporate one more acetate unit than common ustilaginoidins. Ustilaginoidin W (<b>8</b>) is a rare formate-containing bis-naphtho-γ-pyrone. Ustilaginoidins R (<b>2</b>), U (<b>6</b>), B (<b>17</b>), and I (<b>24</b>) showed moderate inhibitory activities toward the radicle or germ elongation of rice seeds. Ustilaginoidins R (<b>2</b>), S (<b>3</b>), V (<b>7</b>), W (<b>8</b>), B (<b>17</b>), C (<b>18</b>), and H–J (<b>23</b>–<b>25</b>) were cytotoxic to the tested human cancer cell lines (HCT116, NCI-H1650, BGC823, Daoy, and HepG2), with IC₅₀ values in the range of 4.06–44.1 μM

Bioactive Spirobisnaphthalenes from the Endophytic Fungus <i>Berkleasmium</i> sp.

Nine new spirobisnaphthalenes, palmarumycins B₁–B₉ (<b>1</b>–<b>9</b>), along with 13 known compounds (<b>10</b>–<b>22</b>), were isolated from cultures of the fungus <i>Berkleasmium</i> sp., an endophyte isolated from the medicinal plant <i>Dioscorea zingiberensis</i> C. H. Wright. The structures of the new compounds were elucidated by analysis of the 1D and 2D NMR and HRESIMS spectra and by comparison with known compounds. Compounds <b>7</b>–<b>9</b> contain an uncommon 2,3-dihydro-1<i>H</i>-inden-1-one unit. All isolated compounds were evaluated for their antibacterial activities against <i>Bacillus subtilis</i>, <i>Staphylococcus hemolyticus</i>, <i>Agrobacterium tumefaciens</i>, <i>Pseudomonas lachrymans</i>, <i>Ralstonia solanacearum,</i> and <i>Xanthomonas vesicatoria</i> and for their antifungal effects against the spore germination of <i>Magnaporthe oryzae</i>. Palmarumycin C₈ (<b>22</b>) exhibited the best antibacterial and antifungal effects. In addition, diepoxin δ (<b>11</b>) and palmarumycin C₈ (<b>22</b>) showed pronounced cytotoxic activities against five human cancer cell lines (HCT-8, Bel-7402, BGC-823, A 549, A 2780) with IC₅₀ values of 1.28–5.83 μM

Bioactive Dibenzo-α-pyrone Derivatives from the Endophytic Fungus <i>Rhizopycnis vagum</i> Nitaf22

Six new dibenzo-α-pyrones, rhizopycnolides A (<b>1</b>) and B (<b>2</b>) and rhizopycnins A–D (<b>3</b>–<b>6</b>), together with eight known congeners (<b>7</b>–<b>14</b>), were isolated from the endophytic fungus <i>Rhizopycnis vagum</i> Nitaf22 obtained from <i>Nicotiana tabacum</i>. The structures of the new compounds were unambiguously elucidated using NMR, HRESIMS, TDDFT ECD calculation, and X-ray crystallography data. Rhizopycnolides A (<b>1</b>) and B (<b>2</b>) feature an uncommon γ-butyrolactone-fused dibenzo-α-pyrone tetracyclic skeleton (6/6/6/5), while rhizopycnin B (<b>4</b>) was the first amino group containing dibenzo-α-pyrone. Rhizopycnolides A (<b>1</b>) and B (<b>2</b>) are proposed to be biosynthesized from polyketide and tricarboxylic acid cycle pathways. The isolated compounds were tested for their antibacterial, antifungal, and cytotoxic activities. Among them, rhizopycnolide A (<b>1</b>), rhizopycnins C (<b>5</b>) and D (<b>6</b>), TMC-264 (<b>8</b>), penicilliumolide D (<b>11</b>), and alternariol (<b>12</b>) were active against the tested pathogenic bacteria <i>Agrobacterium tumefaciens</i>, <i>Bacillus subtilis</i>, <i>Pseudomonas lachrymans</i>, <i>Ralstonia solanacearum</i>, <i>Staphylococcus hemolyticus</i>, and <i>Xanthomonas vesicatoria</i> with MIC values in the range 25–100 μg/mL. Rhizopycnin D (<b>6</b>) and TMC-264 (<b>8</b>) strongly inhibited the spore germination of <i>Magnaporthe oryzae</i> with IC₅₀ values of 9.9 and 12.0 μg/mL, respectively. TMC-264 (<b>8</b>) showed potent cytotoxicity against five human cancer cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780) with IC₅₀ values of 3.2–7.8 μM

Bioactive Dibenzo-α-pyrone Derivatives from the Endophytic Fungus <i>Rhizopycnis vagum</i> Nitaf22

Six new dibenzo-α-pyrones, rhizopycnolides A (<b>1</b>) and B (<b>2</b>) and rhizopycnins A–D (<b>3</b>–<b>6</b>), together with eight known congeners (<b>7</b>–<b>14</b>), were isolated from the endophytic fungus <i>Rhizopycnis vagum</i> Nitaf22 obtained from <i>Nicotiana tabacum</i>. The structures of the new compounds were unambiguously elucidated using NMR, HRESIMS, TDDFT ECD calculation, and X-ray crystallography data. Rhizopycnolides A (<b>1</b>) and B (<b>2</b>) feature an uncommon γ-butyrolactone-fused dibenzo-α-pyrone tetracyclic skeleton (6/6/6/5), while rhizopycnin B (<b>4</b>) was the first amino group containing dibenzo-α-pyrone. Rhizopycnolides A (<b>1</b>) and B (<b>2</b>) are proposed to be biosynthesized from polyketide and tricarboxylic acid cycle pathways. The isolated compounds were tested for their antibacterial, antifungal, and cytotoxic activities. Among them, rhizopycnolide A (<b>1</b>), rhizopycnins C (<b>5</b>) and D (<b>6</b>), TMC-264 (<b>8</b>), penicilliumolide D (<b>11</b>), and alternariol (<b>12</b>) were active against the tested pathogenic bacteria <i>Agrobacterium tumefaciens</i>, <i>Bacillus subtilis</i>, <i>Pseudomonas lachrymans</i>, <i>Ralstonia solanacearum</i>, <i>Staphylococcus hemolyticus</i>, and <i>Xanthomonas vesicatoria</i> with MIC values in the range 25–100 μg/mL. Rhizopycnin D (<b>6</b>) and TMC-264 (<b>8</b>) strongly inhibited the spore germination of <i>Magnaporthe oryzae</i> with IC₅₀ values of 9.9 and 12.0 μg/mL, respectively. TMC-264 (<b>8</b>) showed potent cytotoxicity against five human cancer cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780) with IC₅₀ values of 3.2–7.8 μM

Bioactive Bis-naphtho-γ-pyrones from Rice False Smut Pathogen Ustilaginoidea virens

Ustilaginoidins were bis-naphtho-γ-pyrones mycotoxins possessing an a<i>R</i> configuration of the chiral axis previously reported from the false smut balls of rice infected by the fungal pathogen Ustilaginoidea virens. To investigate the chemical diversity of these metabolites and their bioactivities, we fermented this fungus on solid rice media, which afforded the isolation of 13 ustilaginoidins, including seven new compounds, namely ustilaginoidins K–P, <b>1</b>–<b>6</b>, and E₁, <b>7</b>, together with the known ustilaginoidins A, <b>8</b>, D, <b>9</b>, E, <b>10</b>, F, <b>11</b>, and G, <b>12</b>, and isochaetochromin B₂, <b>13</b>. The structures of the new compounds were elucidated by using (1D, 2D) NMR, high-resolution mass spectrometry, UV, and circular dichroism, as well as by comparison with the literature data. A plausible biosynthesis pathway was proposed for these dimeric polyketides. The isolated compounds were evaluated for their antibacterial, cytotoxic, and radicle elongation inhibitory activities. Ustilaginoidins K, <b>1</b> and L, <b>2</b> showed cytotoxic activities on the A2780 human ovarian cancer cell line with IC₅₀ values of 4.18 and 7.26 μM, respectively. Ustilaginoidins N, <b>4</b>, D, <b>9</b>, E, <b>10</b>, and G, <b>12</b> were active against the tested pathogenic bacteria with MIC values in the range of 16–64 μg/mL. Ustilaginoidins O, <b>5</b>, E, <b>10</b>, and F, <b>11</b>, and isochaetochromin B_2, <b>13</b> displayed moderate inhibitory activity on the radicle elongation of rice seeds