Tubakialactones A–E,new polyketides from the endophytic fungus Tubakia sp. ECN-111

Three new isocoumarins and two new phthalides, tubakialactones A–E (1–5), together with three known polyketides including (R)-3,4-dihydro-4-hydroxyl-6,8-dimethoxy-4-methyl-3-methylene-1H-2-benzopyran-1-one (6), (?)-5,7-dimethoxy-3-methyl-1(3H)-isobenzofuranone (7), and isosclerone (8) were found in the endophytic fungus Tubakia sp. ECN-111 isolated from the leaves of Houttuynia cordata. The chemical structures of the new compounds were determined by spectroscopic analyses, including extensive 2D-NMR experiments. The absolute configuration of 3 and 7 was determined by optical rotation and circular dichroism.     

Globostelletins J–S,isomalabaricanes with unusual cyclopentane sidechains from the marine sponge Rhabdastrella globostellata

Nine new isomalabaricane-type triterpenoids namely globostelletins J–R (1–9) were isolated from the marine sponge Rhabdastrella globostellata. Their structures were established on the basis of extensive spectroscopic data analysis including IR, MS, 1D and 2D NMR, and CD spectra. Globostelletins J–R are characterized by the presence of an unusual cyclopentane unit linked at different positions of sidechains. These unprecedented structures enriched a number of new skeletons in isomalabaricane family. The biogenetic relationship of the isolated compounds is postulated. All compounds were tested for the inhibitory activities against human tumor-related protein kinases.     

Euryjanicins E–G,poly-phenylalanine,and poly-proline cyclic heptapeptides from the Caribbean sponge Prosuberites laughlini

A new investigation of the active sponge extracts of Prosuberites laughlini collected off the West coast of Puerto Rico has yielded three new cyclic heptapeptides, namely euryjanicins E (1)–G (3), containing multiple phenylalanine and proline residues. In CDCl₃ solution, each euryjanicin F (2) and G (3) exists as an inseparable complex mixture of conformational isomers. The molecular structures of 1–3 were elucidated by a combination of chemical degradation, extensive ESI-MS/MSⁿ analyses, and 2D NMR methods. The elucidation of the absolute configuration was achieved by HPLC following analysis of the acid hydrolysates after derivatization with Marfey's reagent. When assayed against the National Cancer Institute 60 tumor cell line panel, the new cyclic peptides did not display significant in vitro cytotoxicity.     

Fusopoltides B–E,new polyketides isolated from Fusarium solani B-18

Four new polyketides, fusopoltides B–E, were isolated, along with four known compounds, from Fusarium solani B-18 cultured on brown-rice. Fusopoltide B is a diastereomer of its co-isolated known compound, fusopoltide A, featuring a pentaleno[1,2-c]pyran ring system. Fusopoltide C and fusopoltides D–E are incorporated the first natural polyketides featured decahydro-pentaleno[1,2-c]pyran and pentaleno[1,2-c]furan ring systems, respectively. The structural assignments were established using comprehensive spectroscopic techniques, the modified Mosher's ester method, and electronic circular dichroism (ECD) calculations.     

The in vivo anti-plasmodial activity of haliclonacyclamine A, an alkaloid from the marine sponge, Haliclona sp

The compound haliclonacyclamine A was isolated from the Haliclona sponge at Solomon Islands. It acts as a powerful in?vitro and in?vivo anti-plasmodial agent against the chloroquine-resistant Plasmodium falciparum strain FCB1and Plasmodium vinckei petteri-infected mice, respectively.     

Monamphilectine A, a potent antimalarial β-lactam from marine sponge Hymeniacidon sp: isolation, structure, semisynthesis, and bioactivity

Monamphilectine A (1), a new diterpenoid β-lactam alkaloid showing potent antimalarial activity, was isolated in milligram quantities following bioassay-directed extraction of a Puerto Rican marine sponge Hymeniacidon sp. Its structure, established by interpretation of spectral data, was confirmed unequivocally by chemical interconversion and comparison of physical, chemical, and bioactivity data with the natural product. The one-step semisynthesis of monamphilectine A was based on a multicomponent Ugi reaction that also established its absolute stereostructure.     

Cyclodysidins A–D,cyclic lipopeptides from the marine sponge-derived Streptomyces strain RV15

Four new cyclic lipopeptides, cyclo-(AFA-Ser-Gln-Asn-Tyr-Asn-Ser-Thr), named cyclodysidins A–D, were isolated from the broth culture of Streptomyces strain RV15 associated with the marine sponge Dysidea tupha. The sequences of the amino acid building blocks in the compounds and their structures were determined by 1D- and 2D-NMR techniques and CID-MS/MS experiments. The absolute configurations of all α-amino acids were determined by HPLC analysis after derivatization with Marfey’s reagent and comparison with commercially available reference samples, while those two of the β-amino fatty acids were determined by using racemic and enantiopure reference samples synthetically prepared.     

Pleosporalesones A–B,two unique polyketides isolated from Pleosporales sp.

Two unique polyketides, pleosporalesones A–B (1–2), bearing an unusual 6/6/7/6 tetracyclic ring system consisting of a chromone ring and a benzoannulated cycloheptanone ring, were isolated from the solid cultures of Pleosporales sp.. The chemical structures were elucidated by analyses of their extensive spectroscopic data, including 1D/2D NMR, ORD, CD and HR-ESI-MS, and the absolute configurations were established by comparison of their experimental circular dichroism data with those calculated. A plausible biosynthetic pathway for pleosporalesones A–B was proposed.     

Viscosalines B(1,2) and E(1,2): challenging new 3-alkyl pyridinium alkaloids from the marine sponge Haliclona viscosa

Four new 3-alkyl pyridinium alkaloids, the viscosalines?B(1) (1?a), B(2) (1?b), E(1) (2?a), and E(2) (2?b), were isolated from the Arctic sponge Haliclona viscosa. The structure elucidation of these isomeric compounds was challenging due to ambiguous fragments that derive during "standard" mass spectrometric fragmentation experiments. The final structure elucidation relied on the use of a combination of synthesis, liquid chromatography, and mass spectrometry. Three different mass spectrometers were used to differentiate between the synthetic structural isomers: a time-of-flight (TOF) mass spectrometer and two ion-trap mass spectrometers with different ion-transfer technologies (i.e., skimmer versus funnel optics). Although at first none of the spectrometers returned spectra that permitted structure elucidation, all three mass spectrometers provided analysis that successfully differentiated between the isomers after thorough method optimization. The use of in-source collision-induced dissociation (CID) with the ion trap and TOF instrument returned the most interesting results. The mode of fragmentation of the viscosalines under different experimental conditions is described herein. After successful optimization of the mass spectrometric method applied, the chromatographic method was improved to distinguish the previously inseparable isomers. Finally, both the liquid chromatography and mass spectrometric methods were applied to the natural products and the results compared to those from the synthetic compounds.     

(−)-Wistarin from the marine sponge Ircinia sp.: the first case of enantiomeric sesterterpenes

The sestertepene (−)-wistarin has been isolated from a Red Sea sponge of the genus Ircinia. This metabolite is the enantiomer of (+)-wistarin, a tetracyclic metabolite previously isolated from the sponge Ircinia wistarii. The enantiomeric relationship was proved by comparison of the CD spectrum of (−)-wistarin with that of a synthetic sample of the (+)-isomer. A hypothetical biosynthesis of (−)-wistarin is discussed starting from a putative linear precursor.     

Iodo–sesquiterpene hydroquinone and brominated indole alkaloids from the Thai sponge Smenospongia sp.

6′-Iodoaureol, an iodo–sesquiterpene hydroquinone, 6′-aureoxyaureol, a bissesquiterpene hydroquinone, and four brominated indole alkaloids 3–6 were isolated from the Thai sponge Smenospongia sp. Additionally, four known sesquiterpene hydroquinones 12–15, ten known brominated indole alkaloids 7–11, 17–18, and 20–22, ergosterol, and furospinosulin-1 were also isolated. Compound 1 is the first reported iodo–sesquiterpene hydroquinone and compounds 7–11 were isolated for the first time from natural sources. The structures were characterized by spectroscopic analyses as well as comparison with literature data. Several of these metabolites were evaluated for cytotoxic activity against seven tumor cell lines.     

Agrocybynes A–E from the culture broth of Agrocybe praecox

Five novel compounds (1–3, 5, and 6), and two known ones (4 and 7) were isolated from the culture broth of Agrocybe praecox. Their structures were determined by the interpretation of spectroscopic data. Compounds 1–4 inhibited hypocotyl growth of lettuce, and 1, 3, and 4 inhibited the root growth.     

Globrauneine A–F: six new triterpenoid esters from the leaves of Globimetula braunii

Abstract

Phytochemical study was conducted on the leaves of Globimetula braunii which is a hemi parasitic plant belonging to the family Loranthaceae. Extraction was carried out using cold extraction method with increasing polarity of solvents i.e n-hexane, CH₂Cl₂ and MeOH. The components were separated by chromatographic technique and the structures of the compounds were elucidated by extensive spectroscopic analyses including MS, FTIR, 1D and 2D NMR, HRMS and chemical methods. Six new pentacyclic triterpenoid esters named as globrauneine A (1), globrauneine B (2), globrauneine C (3), globrauneine D (4), globrauneine E (5), and globrauneine F (6), together with six known compounds (7 – 12) were successfully isolated from the leaves of G. braunii growing on Piliostigma thonningii. These results depict a substantial support to the chemotaxonomy of the genus Globimetula.     

Artanomadimers A–F: six new dimeric guaianolides from Artemisia anomala

A novel dimeric guaianolide with an unprecedented skeleton, named artanomadimer A (1), and five new analogues, artanomadimers B–F (2–6), were isolated from the aerial parts of Artemisia anomala. Their structures and stereochemistry were elucidated by extensive spectroscopic methods, and the absolute stereochemistry of compound 4 was confirmed by X-ray crystallographic analysis. Artanomadimer A (1) is probably formed through a Diels–Alder reaction with the new carbon–carbon bond formation of C-11/C-2′ and C-13/C-5′ based on its structure. A cytotoxic evaluation showed that compounds 1 and 6 exhibited significant inhibitory effects against the cell growth of BGC-823 tumor cell lines with IC₅₀ values of 2.71 and 6.25 μM, respectively.     

Heterobimetallic Re–Pd,Re–Au and Re–Cu complexes derived from diphenylphosphino cyrhetrene: Synthesis and X-ray structure

Diphenylphosphinecyrhetrene ligand (η⁵-C₅H₄PPh₂)Re(CO)₃ (1) reacts with 1 equiv. of PdCl₂(NCPh)₂ to form, after workup, the square-planar trans-[(η⁵-C₅H₄PPh₂)Re(CO)₃]PdCl₂(NCMe) (2). Similarly, reaction of 1 with (tetrahydrothiophene)AuCl produces, in excellent yield, the bimetallic complex [(η⁵-C₅H₄PPh₂)Re(CO)₃]AuCl (3) with a linear P–Au–Cl moiety. From the reaction of 2 equiv. of 1 with CuBr(SMe₂) the planar-trigonal complex [(η⁵-C₅H₄PPh₂)Re(CO)₃]₂CuBr (4) was obtained. ³¹P NMR and X-ray crystallography demonstrate, for the three cases, that (η⁵-C₅H₄PPh₂)Re(CO)₃ acts as a monodentate ligand. The structural parameters of the bimetallic complexes are compared with related diphenylphosphinoferrocene metal complexes, described in the literature.     

A new method for estimating the relative binding free energy,derived from a free energy variational principle for the Pim-1-kinase–ligand and FKBP–ligand systems

Journal of Computer-Aided Molecular Design - In this study, a new method is proposed for calculating the relative binding free energy between a ligand and a protein, derived from a free energy...     

Symphyocladins A–G: bromophenol adducts from a Chinese marine red alga,Symphyocladia latiuscula

Chemical analysis of a Chinese collection of the marine red alga Symphyocladia latiuscula yielded five unprecedented bromophenol–aconitic acid adducts, symphyocladins A–E, together with a new example of a bromophenol–pyroglutamic acid adduct, symphyocladin F, a new example of a bromophenol–urea adduct, symphyocladin G, and the known methyl ester of cis-aconitic acid. The structures were assigned on the basis of detailed spectroscopic analysis, and were consistent with a plausible biosynthetic pathway linking these bromophenol natural products with a putative quinone methide intermediate. Symphyocladins A/B and C/D were isolated as inseparable 1:1 mixtures of E/Z isomers. A plausible mechanism for their facile equilibration during handling and storage is presented. The bromophenol–urea exhibits antifungal activity (MIC 10 μg/mL) against Candida albicans.     

Topsendines A–F,new 3-alkylpyridine alkaloids from a Hainan sponge Topsentia sp.

Six new 3-alkylpyridine alkaloids, topsendines A–F (1–6), and one new naturally occurring product, 2-methyl-12-(pyridine-3-yl)dodecanal (7), were isolated from an undescribed species of Hainan sponge Topsentia. The structures of the new compounds were determined by extensive 2D NMR experiments, HR-EI/ESI-MS spectrometry measurements, and by comparison of their NMR data with those of structurally related compounds in the literature. In bioassay, compounds 1, 3, and 5 showed inhibitory actions on delayed rectifier K⁺ currents (I_K) in rat acutely dissociated hippocampal neurons at the concentration of 100 μM, with the percentage of inhibition of 85.9±3.9%, 87.1±4.4%, and 76.2±12.2%, respectively.     

A convergent total synthesis of the marine sponge alkaloid ageladine A via a strategic 6π-2-azatriene electrocyclization

A second generation total synthesis of the marine sponge metabolite ageladine A utilizing a biogenetically inspired 6π-2-azaelectrocyclization of triene 34 as the key step is performed to construct the imidazopyridine core of the metabolite.