A new isomaneonene derivative from the red alga <i>Laurencia</i> cf. <i>mariannensis</i>

Determining the structures of new natural products from marine species not only enriches our understanding of the diverse chemistry of these species, but can also lead to the discovery of compounds with novel and/or important biological activities. Herein, we describe the isolation of isomaneonene C (1), a new halogenated C15 acetogenin, and three known compounds, α-snyderol (2), cis-maneonene D (3), and isomaneonene B (4), from the organic extract obtained from the red alga Laurencia cf. mariannensis collected from Iheya Island, Okinawa, Japan. The structures of these secondary metabolites were elucidated spectroscopically. All compounds were inactive at 30 μg/disc against methicillin-resistant Staphylococcus aureus (MRSA) in combination treatment with a β-lactam drug, meropenem. </p

Akedanones A–C, <i>In Vitro</i> and <i>In Vivo</i> Antiplasmodial 2,3-Dihydronaphthoquinones Produced by Streptomyces sp. K20-0187

Three new antiplasmodial compounds, named akedanones A (1), B (2), and C (3), were discovered from the cultured material of Streptomyces sp. K20-0187 isolated from a soil sample collected at Takeda, Kofu, Yamanashi prefecture in Japan. The structures of compounds 1–3 were elucidated as new 2,3-dihydronaphthoquinones having prenyl and reverse prenyl groups by mass spectrometry and nuclear magnetic resonance analyses. Compound 1 and the known furanonaphthoquinone I (4) showed potent in vitro antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with half-maximal inhibitory concentration values ranging from 0.06 to 0.3 μM. Compounds 1 and 4 also displayed potent in vivo antiplasmodial activity against drug-sensitive rodent malaria Plasmodium berghei N strain, with inhibition rates of 47.6 and 43.1%, respectively, on intraperitoneal administration at a dose of 5 mg kg–1 day–1 for 4 days

Akedanones A–C, <i>In Vitro</i> and <i>In Vivo</i> Antiplasmodial 2,3-Dihydronaphthoquinones Produced by Streptomyces sp. K20-0187

Three new antiplasmodial compounds, named akedanones A (1), B (2), and C (3), were discovered from the cultured material of Streptomyces sp. K20-0187 isolated from a soil sample collected at Takeda, Kofu, Yamanashi prefecture in Japan. The structures of compounds 1–3 were elucidated as new 2,3-dihydronaphthoquinones having prenyl and reverse prenyl groups by mass spectrometry and nuclear magnetic resonance analyses. Compound 1 and the known furanonaphthoquinone I (4) showed potent in vitro antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with half-maximal inhibitory concentration values ranging from 0.06 to 0.3 μM. Compounds 1 and 4 also displayed potent in vivo antiplasmodial activity against drug-sensitive rodent malaria Plasmodium berghei N strain, with inhibition rates of 47.6 and 43.1%, respectively, on intraperitoneal administration at a dose of 5 mg kg–1 day–1 for 4 days

Isolation and Total Synthesis of Hoshinolactam, an Antitrypanosomal Lactam from a Marine Cyanobacterium

In the search for new antiprotozoal substances, hoshinolactam, an antitrypanosomal lactam, was isolated from a marine cyanobacterium. The gross structure was elucidated by spectroscopic analyses, and the absolute configuration was determined by the first total synthesis. Hoshinolactam showed potent antitrypanosomal activity with an IC₅₀ value of 3.9 nM without cytotoxicity against human fetal lung fibroblast MRC-5 cells (IC₅₀ > 25 μM)

Herquline A, produced by <i>Penicillium herquei</i> FKI-7215, exhibits anti-influenza virus properties

<p>In the course of screening for new anti-influenza virus antibiotics, we isolated herquline A from a culture broth of the fungus, <i>Penicillium herquei</i> FKI-7215. Herquline A inhibited replication of influenza virus A/PR/8/34 strain in a dose-dependent manner without exhibiting cytotoxicity against several human cell lines. It did not inhibit the viral neuraminidase.</p

Total Synthesis of Fusaramin, Enabling Stereochemical Elucidation, Structure–Activity Relationship, and Uncovering the Hidden Antimicrobial Activity against Plant Pathogenic Fungi

Fusaramin (1) was isolated as a mitochondrial inhibitor. However, the fungal producer stops producing 1, which necessitates us to supply 1 by total synthesis. We proposed the complete stereochemical structure based on the biosynthetic pathway of sambutoxin. We have established concise and robust total synthesis of 1, enabling us to determine the complete stereochemical structure and to elucidate the structure–activity relationship, and uncover the hidden antiplant pathogenic fungal activity

Aogacillins A and B Produced by <i>Simplicillium</i> sp. FKI-5985: New Circumventors of Arbekacin Resistance in MRSA

Aogacillins A and B, capable of overcoming arbekacin resistance in methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), were isolated from a culture broth of <i>Simplicillium</i> sp. FKI-5985. Their structures were elucidated by NMR spectroscopic studies and ECD analyses. The aogacillins possessed a novel carbon skeleton, including a β-keto-γ-methyliden-δ-lactone ring connected to a 2-ethyl-6-methylcyclohexane ring by spiro conjugation

Design and <i>De Novo</i> Synthesis of 6‑Aza-artemisinins

Development of designer natural product variants, 6-aza-artemisinins, enabled us to achieve structural modification of the hitherto unexplored cyclohexane moiety of artemisinin and concise <i>de novo</i> synthesis of the tetracyclic scaffold in just four steps from the modular assembly of three simple building blocks. This expeditious catalytic asymmetric synthetic approach generated lead candidates exhibiting superior <i>in vivo</i> antimalarial activities to artemisinin

Chemical Degradation-Inspired Total Synthesis of the Antibiotic Macrodiolide, Luminamicin

This article describes the first total synthesis of luminamicin using a strategy combining chemical degradation with synthesis. Chemical degradation studies provided a sense of the inherent reactivity of the natural product, and deconstruction of the molecule gave rise to a key intermediate, which became the target for chemical synthesis. The core structure of the southern part of luminamicin was constructed by a 1,6-oxa-Michael reaction to form an oxa-bridged ring, followed by coupling with a functionalized organolithium species. Modified Shiina macrolactonization conditions forged the strained 10-membered lactone containing a tri-substituted olefin. Diastereoselective α-oxidation of the 10-membered lactone completed the center part to provide the key intermediate. Inspired by the degradation study, an unprecedented enol ether/maleic anhydride moiety was constructed with a one-pot chlorosulfide coupling and thiol β-elimination sequence. Finally, macrolactonization to the 14-membered ring in the presence of the highly electrophilic maleic anhydride moiety was accomplished using modified Mukaiyama reagents to complete the synthesis of luminamicin

Sucupiranins A–L, Furanocassane Diterpenoids from the Seeds of <i>Bowdichia virgilioides</i>

Twelve new furanocassane diterpenoids, sucupiranins A–L (<b>1</b>–<b>12</b>), and three known compounds (<b>13</b>–<b>15</b>) were isolated from the seeds of <i>Bowdichia virgilioides</i>. The structures of the compounds were elucidated via ¹H and ¹³C NMR analysis, including 2D NMR (¹H–¹H COSY, HSQC, HMBC, and NOESY); HRMS data; and X-ray crystallographic analysis. The absolute configurations were defined using their electronic circular dichroism (ECD) spectra by applying the exciton chirality method to the bis-<i>p</i>-bromobenzoate of compound <b>13</b>. Sucupiranin J (<b>10</b>) inhibited lipopolysaccharide-induced nitric oxide production (IC₅₀ 30.6 μM), whereas sucupiranins J (<b>10</b>), K (<b>11</b>), and <b>13</b> exhibited weak antimalarial activity against <i>Plasmodium falciparum</i> K1 with IC₅₀ values of 32.2, 23.5, and 22.9 μM and selectivity indices of 4.3, 1.9, and >12.0 (MRC-5/K1), respectively