Unprecedented Carbon Skeleton Research Articles

Aphadilactones A–D, Four Diterpenoid Dimers with DGAT Inhibitory and Antimalarial Activities from a Meliaceae Plant

Aphadilactones A-D (1-4), four diastereoisomers possessing an unprecedented carbon skeleton, were isolated from the Meliaceae plant Aphanamixis grandifolia. Their challenging structures and absolute configurations were determined by a combination of spectroscopic data, chemical degradation, fragment synthesis, experimental CD spectra, and ECD calculations. Aphadilactone C (3) with the 5S,11S,5'S,11'S configuration showed potent and selective inhibition against the diacylglycerol O-acyltransferase-1 (DGAT-1) enzyme (IC50 = 0.46 ± 0.09 μM, selectivity index > 217) and is the strongest natural DGAT-1 inhibitor discovered to date. In addition, compounds 1-4 showed significant antimalarial activities with IC50 values of 190 ± 60, 1350 ± 150, 170 ± 10, and 120 ± 50 nM, respectively.

Caesalminaxins A–L, Cassane Diterpenoids from the Seeds of Caesalpinia minax

Fourteen new cassane diterpenoids, caesalminaxins A-L (1-14), and three known compounds were isolated from the seeds of Caesalpinia minax. Among the new diterpenoids, compounds 3 and 4 possess a rare spiro C/D ring system. The C-16 epimeric mixture 1/2 has an unprecedented carbon skeleton, presumably derived from 3 by cleavage of the C-13-C-14 bond. Compound 5 is the first example of a cassane diterpenoid with a spiro A/B ring system. The structures of the compounds were elucidated on the basis of 1D and 2D NMR analysis, and the absolute configurations of 3, 4, 9, and 11 were determined by single-crystal X-ray crystallography. Biosynthesis pathways for 1/2, 3, and 5 are postulated. Compounds 4, 8, and the known bonducellpin D exhibited moderate activity against four tested human cancer cell lines, HepG-2, K562, HeLa, and Du145.

Hippolachnin A, a New Antifungal Polyketide from the South China Sea Sponge Hippospongia lachne

Hippolachnin A (1), a polyketide possessing an unprecedented carbon skeleton with a four-membered ring, was isolated from the South China Sea sponge Hippospongia lachne. The structure was elucidated using MS and NMR spectroscopic analyses, and the absolute configuration was determined using a calculated ECD method. Hippolachnin A demonstrated potent antifungal activity against three pathogenic fungi, Cryptococcus neoformans, Trichophyton rubrum, and Microsporum gypseum, with a MIC value of 0.41 μM for each fungus.

Micranthanone A, a New Diterpene with an Unprecedented Carbon Skeleton from Rhododendron micranthum

A new diterpene with an unprecedented carbon skeleton, micranthanone A (1), two new grayanane diterpenoids bearing an unusual 5,6-(3,4-dihydroxylbenzylidene acetal) motif, rhodomicranols A (2) and B (3), and three known grayanane diterpenoids (4-6) were isolated from Rhododendron micranthum. Their structures were elucidated by spectroscopic analyses, calculated ECD, and single-crystal X-ray diffraction. The in vitro immunomodulatory activities of 1-6 were evaluated, and a plausible biogenetic pathway for 1 is proposed.

Guianolides A and B, New Carbon Skeletal Limonoids from the Seeds of Carapa guianensis

Two novel limonoids, named guianolides A (1) and B (2), were isolated from the seeds of Carapa guianensis AUBLET (Meliaceae). Their structures were established by spectroscopic analyses and X-ray crystallography. Guianolides A (1) and B (2) featured an unprecedented carbon skeleton via the formation of a C-11-C-21 bond.

New abietane diterpenoids from the roots of Salvia przewalskii

In an antibiotic screening program for new drug leads, we discovered a seco-norabietane diterpenoid with an unprecedented carbon skeleton, salprzelactone (1), together with three new abietanoids (2–4) from the roots of Salvia przewalskii. Their structures were mainly elucidated by NMR and MS data. The structures of 1 and 4 were elucidated by comprehensive spectroscopic and a single-crystal X-ray crystallographic analysis with the absolute configuration determined by the CD approach coupled with theoretical CD spectra. Those compounds were evaluated for their antibacterial activities against six bacteria.

New Inhibitors of ROS Generation and T-Cell Proliferation from Myrtus communis

Phytochemical investigation on Myrtus communis Linn. afforded myrtucommuacetalone (1) with an unprecedented carbon skeleton and a new phloroglucinol-type compound, myrtucommulone M (2), along with four known constituents 3-6. Their structures were established by extensive analyses of NMR and mass spectral data as well as by single-crystal X-ray diffraction studies. These constituents were evaluated for their ability to modulate the immune response, based on their effects on various components of immune system. Compounds 1 and 5 exhibited significant inhibitory effect against nitric oxide (NO(•)) production. Compound 1 also exhibited significant antiproliferative activity (IC50 < 0.5 μg/mL) against T-cell proliferation. Myricetin (3) exerted a significant inhibition (IC50 = 1.6 μg/mL) on zymosan-stimulated whole blood phagocytes ROS production. Compounds 1 and 3 were active against PMA-stimulated ROS generation.

Myriberine A, a New Alkaloid with an Unprecedented Heteropentacyclic Skeleton from Myrioneuron faberi

Myriberine A (1) possessing an unprecedented carbon skeleton was isolated from Myrioneuron faberi. The structure and absolute configuration of 1 were elucidated by a combination of spectroscopic data, X-ray crystallographic, and computational methods. Myriberine A (1) demonstrated inhibition against the hepatitis C virus (HCV) life cycle in vitro.

Pseudolarenone, an unusual nortriterpenoid lactone with a fused 5/11/5/6/5 ring system featuring an unprecedented bicyclo[8.2.1]tridecane core from Pseudolarix amabilis

A phytochemical investigation of the cone of Pseudolarix amabilis led to the isolation of pseudolarenone (), a structurally novel pentacyclic (5/11/5/6/5) nortriterpenoid lactone with an unprecedented carbon skeleton featuring a unique bicyclo[8.2.1]tridecane core. Its structure and absolute configurations were elucidated by spectroscopic analysis and single crystal X-ray diffraction (CuK(α)).

Kadcoccitones A and B, Two New 6/6/5/5-Fused Tetracyclic Triterpenoids from Kadsura coccinea

A pair of new triterpenoid epimers, kadcoccitones A (1) and B (2), together with a new biogenetically related compound kadcoccitone C (3), were isolated from Kadsura coccinea. The epimers featured an unprecedented carbon skeleton with a 6/6/5/5-fused tetracyclic ring system unit and a C(9) side chain. Their structures were determined by spectroscopic data, ECD calculation, and single-crystal X-ray diffraction. Compounds 1 and 3 showed anti-HIV-1 activity with an EC(50) value of 47.91 and 32.66 μg/mL, respectively.

Brominated Aromatic Furanones and Related Esters from the Ascidian Synoicum sp.

Nine new compounds, tris-aromatic furanones (1, 2, 3a, 3b, and 4) and related bis-aromatic diesters (5a, 5b, 6a, and 6b), are described from the ascidian Synoicum sp. collected off the coast of Chuja-do, Korea. The structures of these compounds, designated as cadiolides E and G-I (1-4) and synoilides A and B (5 and 6), were determined by extensive spectroscopic analyses. The absolute configuration at the asymmetric center of cadiolide G (2) was assigned by ECD analysis. Of these new compounds, cadiolide I and the synoilides possess unprecedented carbon skeletons. Several of these compounds exhibited significant inhibition against diverse bacterial strains as well as moderate inhibition against the enzymes sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase.

Conosilane A, an Unprecedented Sesquiterpene from the Cultures of Basidiomycete Conocybe siliginea

Conosilane A (1), a novel sesquiterpene with an unprecedented carbon skeleton, was isolated from the cultures of the basidiomycete Conocybe siliginea. Its structure was elucidated by extensive spectroscopic methods, and the absolute configuration was determined by single crystal X-ray diffraction analysis. Conosilane A was found to inhibit 11β-hydroxysteroid dehydrogenase significantly.

B-norsteroids from Hymenoscyphus pseudoalbidus

Two viridin-related B-norsteroids, B-norviridiol lactone (1) and B-norviridin enol (2), both possessing distinct unprecedented carbon skeletons, were isolated from a liquid culture of the ash dieback-causing fungus Hymenoscyphus pseudoalbidus. Compound 2 was found to degrade to a third B-norsteroidal compound, 1β-hydroxy-2α-hydro-asterogynin A (3), which was later detected in the original culture. The proposed structure of 1 is, regarding connectivity, identical to the original erroneous structure for TAEMC161, which was later reassigned as viridiol. Compound 2 showed an unprecedented 1H–13C HMBC correlation through an intramolecular hydrogen bond. The five-membered B-ring of compounds 1-3 was proposed to be formed by a benzilic acid rearrangement. The known compound asterogynin A was found to be formed from 3 by a β-elimination of water. All compounds were characterized by NMR spectroscopy, LC-HRMS and polarimetry.

Relative and Absolute Configuration of Vatiparol (1 mg): A Novel Anti‐inflammatory Polyphenol

Bioactive natural products offer multiple opportunities for the discovery of novel chemical entities with potential pharmaceutical, nutraceutical and agrochemical applications. Many new organic compounds with novel scaffolds are isolated in small quantities and established methods often fail to determine the structure and bioactivity of such novel natural products. To meet this challenge, we present here a new methodology combining RDC (residual dipolar coupling)-based NMR spectroscopy in microtubes, with a motif-inspired biological assessment strategy. Using only one milligram (ca. 1.5 μmol) of sample, the new protocol established the bioactivity as well as the relative and absolute configuration of vatiparol obtained from Vatica parvifolia. Vatiparol is unique in its unprecedented carbon skeleton and selective inhibitory effect on the expression of monocyte chemo-attractant protein-1 (MCP-1, also known as CCL2). The plausible biosynthetic pathway of vatiparol is briefly discussed. The approach introduced here promises to be widely applicable to the determination of the structure and bioactivity of structurally unknown organic samples available in very limited amounts.

Hydrangdione C, a novel triterpenoid with an unprecedented skeleton from Salvia hydrangea DC. ex Benth

The genus Salvia is a rich source of terpenoids with structural diversity. Apart from sesterterpenoids as unusual constituents of Salvia species [1,2], it is a source of di- and triterpenoids with unprecedented carbon skeletons [3]. Aiming at identifying structurally interesting and bioactive metabolites from the Salvia species, we examined the extract of Salvia hydrangea DC. ex Benth. In our search for new bioactive natural products, a novel triterpenoid (hydrangdione C, 1) was isolated from the hexane extract of this plant. The skeletal type displayed by hydrangdione C was noticeable for its unusual carbon ring skeleton with a unique five membered ring D substituted by an acetyl group. This is the first report of a natural triterpenoid with a five-membered ring D. The structure of 1 was established by comprehensive 1D NMR, 2D NMR, and HRMS spectroscopic analysis and subsequently confirmed by a single-crystal X-ray diffraction study.

ChemInform Abstract: Styrylpyrone‐Class Compounds from Medicinal Fungi Phellinus and Inonotus spp., and Their Medicinal Importance

AbstractReview: 76 refs.

ChemInform Abstract: Aspergilones A and B, Two Benzylazaphilones with an Unprecedented Carbon Skeleton from the Gorgonian‐Derived Fungus Aspergillus sp.

AbstractAspergilone A(I) possessing an azaphilone structure, and its symmetrical dimer with a unique methylene bridge, aspergilone B(II), are isolated from the culture broth of the marine derived title plant.

ChemInform Abstract: Neojaponicone A, a Bioactive Sesquiterpene Lactone Dimer with an Unprecedented Carbon Skeleton from Inula japonica.

AbstractCompound (I) has an unprecedented carbon skeleton with an unusual valerolacton system formed between a guaianolide and an eudesmane.

Fusarisetin A, an Acinar Morphogenesis Inhibitor from a Soil Fungus, Fusarium sp. FN080326

An acinar morphogenesis inhibitor named fusarisetin A (1) that possesses both an unprecedented carbon skeleton and a new pentacyclic ring system has been identified from an in-house fractionated fungal library using a three-dimensional matrigel-induced acinar morphogenesis assay system. The structure of 1 was determined in detail by NMR and circular dichroism spectroscopy, X-ray analysis, and chemical reaction experiments.

Styrylpyrone-class compounds from medicinal fungi Phellinus and Inonotus spp., and their medicinal importance

Members of the genera Phellinus and Inonotus, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus are well-known medicinal fungi (mushrooms) and have been used in treatment of cancer, diabetes, bacterial and viral infections and ulcer. Adverse effects of these medicinal mushrooms have not yet been reported, indicating the safe nature of these mushrooms. Polysaccharides, particularly β-glucan, are considered the compounds responsible for the biological activity of medicinal mushrooms. However, there is only a limited amount of evidence to indicate that polysaccharides are in fact responsible for the biological effects of these medicinal mushrooms. Recently, many research groups have begun identification of active low-MW compounds in medicinal mushrooms, with a focus on the yellow polyphenol pigments, which are composed of a styrylpyrone class of compounds. Interestingly, a representative group of medicinal fungi, including P. linteus, P. igniarius, P. ribis, I. obliquus and I. xeranticus were shown to produce a large and diverse range of styrylpyrone-type polyphenol pigments that exhibited various biological activities, including anti-oxidative, anti-inflammatory, cytotoxic, anti-platelet aggregation, anti-diabetic, anti-dementia and anti-viral effects. Styrylpyrone pigments in mushrooms are thought to have a role similar to that of flavonoids in plants. The unique and unprecedented carbon skeleton of fused styrylpyrone might be an attractive molecular scaffold for pharmacological applications. In this review, the structural diversity, biological effects and biogenesis of styrylpyrone-class polyphenols from medicinal fungi are described.