Protecting Group-Free Total Synthesis of (−)-Lannotinidine B

The first total synthesis of (−)-lannotinidine B, a unique tetracyclic constitutent of <i>Lycopodium annotinum</i>, has been accomplished in 10 steps with 23% overall yield. The completed short and efficient synthesis is characterized with three highly chemo- and/or stereoselective reductive-amination steps to furnish the desired <i>trans</i>-fused 6/6 bicycle and the aza seven-membered ring system, and a direct intramolecular acyloin condensation to deliver the cyclopentanone moiety, as well as successful application of a protecting group-free strategy and an optimal redox order

Protecting Group-Free Total Synthesis of (−)-Lannotinidine B

The first total synthesis of (−)-lannotinidine B, a unique tetracyclic constitutent of <i>Lycopodium annotinum</i>, has been accomplished in 10 steps with 23% overall yield. The completed short and efficient synthesis is characterized with three highly chemo- and/or stereoselective reductive-amination steps to furnish the desired <i>trans</i>-fused 6/6 bicycle and the aza seven-membered ring system, and a direct intramolecular acyloin condensation to deliver the cyclopentanone moiety, as well as successful application of a protecting group-free strategy and an optimal redox order

Acaulide, an Osteogenic Macrodiolide from <i>Acaulium</i> sp. H‑JQSF, an Isopod-Associated Fungus

Acaulide (<b>1</b>), a macrodiolide with an unprecedented framework, was characterized along with its shunt productsacaulones A (<b>2</b>) and B (<b>3</b>)from the culture of <i>Acaulium</i> sp. H-JQSF associated with the isopod <i>Armadillidium vulgare</i>. The spiro-linked 14-, 14-, and 6-membered cycles of <b>1</b> arise likely from iterative intermolecular Michael addition reactions. Biological evaluation in the prednisolone-induced osteoporotic zebrafish demonstrated that <b>1</b> is antiosteoporotic at 0.4 and 2.0 μM

Acaulins A and B, Trimeric Macrodiolides from <i>Acaulium</i> sp. H‑JQSF

Acaulin A (<b>1</b>) and its macrolactone ring-opened congener acaulin B (<b>2</b>) were characterized from the culture of <i>Acaulium</i> sp. H-JQSF (an isopod-associated fungus) as architecturally undescribed trimeric macrodiolides, with the former being antiosteoporotic at 0.4 μM in the prednisolone-induced osteoporotic zebrafish. Identification of acaudiolic acid (<b>3</b>) as the monomeric macrodiolide precursor facilitated the proposal of the acaulin biosynthetic pathway

Citrofulvicin, an Antiosteoporotic Polyketide from <i>Penicillium velutinum</i>

Citrofulvicin (<b>1</b>), along with its early shunt product fulvionol (<b>2</b>), was characterized as a skeletally unprecedented antiosteoporotic agent from a human sputum-derived fungus <i>Penicillium velutinum.</i> The unique citrofulvicin framework is likely formed by a nonenzymatic intermolecular Diels–Alder cycloaddition between heptaketide-based intermediates. Citrofulvicin and fulvionol were demonstrated to be osteogenic at 0.1 μM in the prednisolone-induced osteoporotic zebrafish

<i>p</i>-Terphenyl and Diterpenoid Metabolites from Endophytic <i>Aspergillus</i> sp. YXf3

Six new <i>p</i>-terphenyl derivatives, named 4″-deoxy-3-hydroxyterphenyllin (<b>1</b>), 4″-deoxy-5′-desmethyl-terphenyllin (<b>2</b>), 5′-desmethylterphenyllin (<b>3</b>), 4″-deoxycandidusin A (<b>4</b>), 4,5-dimethoxycandidusin A (<b>5</b>), and terphenolide (<b>6</b>), four new diterpenoids with norcleistanthane (aspergiloid A (<b>12</b>) and aspergiloid B (<b>13</b>)), cleistanthane (aspergiloid C (<b>14</b>)), and isopimarane (aspergiloid D (<b>15</b>)) type skeletons, and five known <i>p</i>-terphenyl compounds (<b>7</b>–<b>11</b>) were isolated from the fermentation broth of the plant endophytic fungus <i>Aspergillus</i> sp. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison of their NMR data with those reported in the literature. Compounds <b>4</b>, <b>6</b>,<b> 7</b>, and <b>9</b> displayed moderate neuraminidase inhibitory activity with IC₅₀ values ranging from 4.34 to 9.17 μM

Genome Mining of Cinnamoyl-Containing Nonribosomal Peptide Gene Clusters Directs the Production of Malacinnamycin

Cinnamoyl-containing nonribosomal peptides (CCNPs) constitute a unique family of actinobacterial secondary metabolites that display a broad spectrum of biological activities. Here, we present a genome mining approach targeting cyclase and is isomerase to discover new CCNPs, which led to the identification of 207 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named malacinnamycin was identified. A plausible biosynthetic pathway for malacinnamycin was deduced by bioinformatics analysis

P450-Modified Ribosomally Synthesized Peptides with Aromatic Cross-Links

Cyclization of linear peptides is an effective strategy to convert flexible molecules into rigid compounds, which is of great significance for enhancing the peptide stability and bioactivity. Despite significant advances in the past few decades, Nature and chemists’ ability to macrocyclize linear peptides is still quite limited. P450 enzymes have been reported to catalyze macrocyclization of peptides through cross-linkers between aromatic amino acids with only three examples. Herein, we developed an efficient workflow for the identification of P450-modified RiPPs in bacterial genomes, resulting in the discovery of a large number of P450-modified RiPP gene clusters. Combined with subsequent expression and structural characterization of the products, we have identified 11 novel P450-modified RiPPs with different cross-linking patterns from four distinct classes. Our results greatly expand the structural diversity of P450-modified RiPPs and provide new insights and enzymatic tools for the production of cyclic peptides

Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus <i>Diaporthe</i> sp.

A new sesquiterpenoid, diaporol A (<b>1</b>), possessing a unique tricyclic lactone framework, eight new drimane sesquiterpenoids, diaporols B–I (<b>2</b>–<b>9</b>), and the known compounds <b>10</b> and <b>11</b> were isolated from a culture of the mangrove-derived endophyte <i>Diaporthe</i> sp. The absolute configurations of <b>1</b>–<b>5</b> were determined by low-temperature (100 K) single-crystal X-ray diffraction with Cu Kα radiation. The compounds were evaluated for cytotoxic activity; however, no compound showed significant cytotoxicity against the tested cell lines at a concentration of 20 μM

Sesquiterpenoids from the Mangrove-Derived Endophytic Fungus <i>Diaporthe</i> sp.

A new sesquiterpenoid, diaporol A (<b>1</b>), possessing a unique tricyclic lactone framework, eight new drimane sesquiterpenoids, diaporols B–I (<b>2</b>–<b>9</b>), and the known compounds <b>10</b> and <b>11</b> were isolated from a culture of the mangrove-derived endophyte <i>Diaporthe</i> sp. The absolute configurations of <b>1</b>–<b>5</b> were determined by low-temperature (100 K) single-crystal X-ray diffraction with Cu Kα radiation. The compounds were evaluated for cytotoxic activity; however, no compound showed significant cytotoxicity against the tested cell lines at a concentration of 20 μM