Aplyronines D–H from the sea hare Aplysia kurodai: isolation,structures, and cytotoxicity

Five cytotoxic macrolides, aplyronines D–H (4–8), were isolated from the Japanese sea hare Aplysia kurodai. They are new congeners of the antitumor compound aplyronine A (1), which was previously isolated from the same organism. Their structures were determined by spectroscopic analysis (NMR and MS). The cytotoxicity of these new compounds was evaluated in comparison with that of aplyronines A–C (1–3), suggesting the importance of the 7-O-seryl ester group for mediating the potent cytotoxicity of aplyronines.     

Rubischumanins A–C,new cytotoxic cyclopeptides from Rubia schumanniana

Three new cyclic hexapeptides, designated as rubischumanins A–C (1–3), together with three known ones (4–6) were isolated from the roots and rhizomes of Rubia schumanniana. The structures were elucidated on the basis of extensive spectroscopic analysis. Cytotoxicity of these compounds was evaluated and compounds 1, 2, 4, and 5 showed cytotoxicity against A549, BGC-823, and Hela cell lines.     

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.     

Alstolactines A–C,novel monoterpenoid indole alkaloids from Alstonia scholaris

Three novel ring-fused monoterpenoid indole alkaloids, alstolactines A–C (1–3), were isolated from the long-term stored leaves of Alstonia scholaris. Their structures were identified on the basis of extensive spectroscopic data and X-ray diffractions. Moreover, the absolute configurations of these related structures were indicated by the crystal X-ray diffractions (Mo Kα) of 1a, a chlorinated derivative of 1.     

Dendronephthols A–C,new sesquiterpenoids from the Red Sea soft coral Dendronephthya sp.

Three new ylangene-type sesquiterpenoids: dendronephthol A (7,13-dihydroxy-3,4-dihydro-α-ylang-5-one) (1), dendronephthol B (6,7,13-trihydroxy-3,4-dihydro-α-ylangene) (2), and dendronephthol C (6,7,13-trihydroxy-α-ylang-5-one) (3), together with two known compounds: dendronesterone A and cholesterol were isolated from the CHCl₃ fraction of Red Sea soft coral Dendronephthya sp. (Nephtheidae). The structures of the new compounds were established on the basis of one- and two-dimensional NMR spectroscopic studies (¹H, ¹³C, DEPT, COSY, HSQC, HMBC, and NOESY) as well as MS spectroscopy and by comparison of the spectral data with those of related known compounds. Compounds 1 and 3 showed cytotoxic activity against the murine lymphoma L5187Y cancer cell line with ED₅₀ values of 8.4 and 6.8 μg/mL, respectively.     

Baeckfrutones A–L,polymethylated phloroglucinol meroterpenoids from the twigs and leaves of Baeckea frutescens

Twelve new polymethylated phloroglucinol meroterpenoids (PPMs), baeckfrutones A–L (1–12), were isolated from the twigs and leaves of Baeckea frutescens. Their structures and absolute configurations were unambiguously established by extensive spectroscopic methods (HRESIMS, NMR, and ECD) and single crystal X-ray diffraction. PPM 1 is a rare PPM comprising enone-type phloroglucinol and α-phellandrene units, whereas 2–4, 6, and 7, are the first hybrids of enone-type phloroglucinol and sabinene moieties with different stereochemistry. (?)-2 and 11 showed remarkable cytotoxicities against DU145 and HCT116?cells with IC₅₀ values of 1.33 and 12.89?μM, respectively. 6, 7, (+)-9, and 10 displayed significant anti-inflammatory activity with inhibitory rates of 74.64, 75.37, 55.13, and 75.01% at the concentration of 50?μM, respectively.     

Ligusaginoids A–D,four eremophilane-type sesquiterpenoid dimers and trimers from Ligularia sagitta

Four novel highly oxygenated eremophilane-type sesquiterpenoid dimers and trimers with the unique 6/6/5/5 polycyclic skeleton, designated as ligusaginoids A–D (1–4), were isolated from the aerial parts of Ligularia sagitta. Their structures with absolute configurations were determined by a combined method. Moreover, a plausible biosynthetic pathway of 1–4 was also proposed. These compounds showed weak antibacterial activities.     

Glabralides A – C,three novel meroterpenoids from Sarcandra glabra

Glabralides A–C (1–3), three novel meroterpenoids including two unprecedented skeletons were isolated from the whole plants of Sarcandra glabra. Glabralide A (1) represented a unique skeleton of the chalcone-coupled monoterpenoid, bearing a bicyclo [2.2.2] octene core unit with five chiral centers. The structures were established by spectroscopic methods, including 2D NMR experiments, and the absolute configurations were determined using circular dichroic (CD) spectra. The plausible biogenetic pathway for 1 suggested that α-phellandrene was conjugated with chalcone by Diels-Alder cyclization, and for 3 implied that α-phellandrene and o-hydroxy phenylacetate cyclized by an uncommon radical addition and cationic cyclization.     

Voacalgines A–E,new indole alkaloids from Voacanga grandifolia

Five new indole alkaloids, voacalgines A–E (1–5) consisting of a C-mavacurine type of skeleton with 2,3-dihydroxybenzoate moiety, a macroline-type of skeleton, or a macroline-type of skeleton with C₆ unit, were isolated from the bark of Voacanga grandifolia. Their relative structures were determined by means of NMR data. Voacalgine A showed moderate cell growth inhibitory activities against HL-60 and HCT116 cells.     

Synthesis of (±)-prepinnaterpene,a bromoditerpene from the red alga Laurencia Pinnata Yamada

A total synthesis of (±)-prepinnaterpene, a brominated diterpene with a unique skeleton, and (±)-oppositol, a related sesquiterpene, is described.     

Amide,cyclohexenone, and cyclohexenone–sordaricin derivatives from the endophytic fungus Xylaria plebeja PSU-G30

Six new compounds, two cyclohexenones, named xylariacyclones A (1) and B (2), three cyclohexenone–sordaricin derivatives, named xylarinonericins A–C (3–5), and one amide derivative, named xylariamide (6), together with 11 known compounds were isolated from the broth extract of the endophytic fungus Xylaria plebeja PSU-G30. The structures were elucidated by analyses of NMR spectroscopic data and chemical methods. Compounds 3–5 are novel and unusual sodaricin derivatives with an ester moiety at C-6 of the sordaricin skeleton. In addition, compound 5 has a unique feature with an ester unit instead of an ether group at C-19. They were evaluated for antifungal activity against Candida albicans ATCC90028 and Cryptococcus neoformans ATCC90113.     

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.     

Fluevirines A–D,four new securinega-type alkaloids from Flueggea virosa

Four new securinega-type alkaloids, fluevirines A–D (1–4), along with ten known ones, were isolated from the twigs and leaves of Flueggea virosa. The structures of the new ones were elucidated by means of spectroscopic methods, and their absolute configurations were assigned by CD spectra. Among them, fluevirine A (1) was a novel C,C-linked dimeric indolizidine alkaloid and showed weak antimicrobial activity against Staphylococcus aureus.     

Claoxylones A–I,prenylbisabolane diterpenoids with anti-Coxsackie B virus activity from the branches and leaves of Claoxylon polot

Nine new prenylbisabolane diterpenoids, claoxylones A–I (1–9), were isolated from the branches and leaves of Claoxylon polot. This is the first example of prenylbisabolane diterpenoids with furan and tetrahydrofuran rings. Their structures and relative configurations were established by spectroscopic and conformational analysis, and the absolute configurations were determined by single-crystal X-ray diffraction and electronic circular dichroism (ECD) analysis. Compounds 1–9 exhibited antiviral activity against Coxsackie B3 virus, with IC₅₀ values of 6.0–33.3 μM.     

The role of new eudesmane-type sesquiterpenoid and known eudesmane derivatives from the red alga Laurencia obtusa as potential antifungal–antitumour agents

A new eudesmane sesquiterpenoid, eudesma-4(15),7-diene-5,11-diol (1) along with the known trinor-sesquiterene, teuhetenone (2), and a seco-eudesmane sesquiterpene, chabrolidione B (3), have been isolated from the Red Sea red alga Laurencia obtusa. The chemical structures were elucidated on the basis of extensive spectroscopic analysis. The antifungal and cytotoxic activities of the isolated metabolites were tested against several fungi, yeast and human mammary carcinoma cell line (MCF-7). Compounds 1 and 3 showed a much better activity [minimum inhibitory concentration (MIC): 2.9 μM] than that of amphotericin B (MIC: 4.6 μM). Interestingly, compound 2, the least active antifungal compound, retained the high anticancer activity against MCF-7 (22 μM) in comparison with cisplatin (59 μM), which was determined by employing lactate dehydrogenase assay. Compounds 1–3 are recorded here for the first time from algal flora. The chemotaxonomic importance of the isolated metabolites was discussed.     

Sydowiols A–C: Mycobacterium tuberculosis protein tyrosine phosphatase inhibitors from an East China Sea marine-derived fungus, Aspergillus sydowii

Chemical analysis of an East China Sea marine-derived fungus, Aspergillus sydowii (MF357) returned three new tris-pyrogallol ethers, sydowiols A–C (1–3), and two known bis-pyrogallol ethers, violaceols I (4) and II (5). Structures were assigned on the basis of detailed spectroscopic analysis and by consideration of symmetry. Sydowiols A (1) and C (3) were responsible for the inhibitory activity detected in the crude fungal extract against Mycobacterium tuberculosis protein tyrosine phosphatase A (PtpA).     

Ivorenoids A–F: limonoids from Khaya ivorensis

Six new limonoids, ivorenoids A–F (1–6), along with ten known analogues, were isolated from an ethanolic extract of the stems of Khaya ivorensis. Their structures were elucidated on the basis of spectroscopic analyses. Compounds 1 and 2 possessed a rare rearranged skeleton of khayanolides and a unique γ-lactone (C-16/C-8) replacing the common and characteristic δ-lactone D-ring (C-16/C-17) of limonoids. A mechanism of the interesting deuteration of H-2 and H-15β of 1, and H-15β of the solvent CD₃OD due to the keto–enol tautomerism was demonstrated. Compounds 3 and 6 showed moderate activity against HL-60 cell line with IC₅₀ values of 15.3 and 17.5 μM, respectively.     

Daphnauranols A–C,new antifeedant sesquiterpenoids with a 5/6/7 ring system from Daphne aurantiaca

Daphnauranols A–C (1–3), three new sesquiterpenoids with an unprecedented 5/6/7 ring system, were isolated from the stems of Daphne aurantiaca Diels. Their structures were elucidated on the basis of comprehensive spectroscopic methods including MS and NMR. The absolute configuration of daphnauranol A was further confirmed by single crystal X-ray diffraction (Cu Kα). Their anti-feedant activity was tested, and the fruit fly antifeedant index (AI) were 39.8 ± 7.2%, 29.4 ± 7.2%, and 26.3 ± 6.4%, respectively.     

Twelve new compounds from Ligularia melanothyrsa; isolation of melanothyrsins A–E,normelanothyrsin A,and other eremophilane sesquiterpenoids

Twelve new compounds, namely, five melanothyrsins A–E (1α-angeloyloxyeremophilenolides), normelanothyrsin A (1α-angeloyloxynoreremophilenone), and six other eremophilane-type compounds, have been isolated from Ligularia melanothyrsa Hand.-Mazz. (Asteraceae), collected in the Sichuan Province of China. Six of the compounds have a 1α-angeloyloxy moiety, while the other six have no functional group at the C-1 position. The absolute configuration was also determined using CD spectra. This is the first chemical study of compounds isolated from this species.     

Violaceimides A–E,sulfur-containing metabolites from a sponge-associated fungus Aspergillus violaceus

Five new methylsuccinimide-based sulfur-bearing compounds, namely violaceimides A–E (1–5), were isolated from the sponge-associated fungal strain Aspergillus violaceus WZXY-m64-17. Their structures were determined by analyses of the HRESIMS, 1D and 2D NMR data, along with the Mosher’s and Snatzke’s methods, experimental and calculated ECD data, as well as chemical conversion for the configurational assignment. The structures of 1–5 featured the fusion of methylsuccinimide with a modified cysteine to incorporate sulfur element, which was found from nature for the first time. The biogenetic relationship of the sulfur-containing compounds was postulated. Violaceimides A and B exerted selective inhibition against the growth of human leukemia U937 and human colorectal cancer cell HCT-8 with low cytotoxicity toward Vero cells, whereas violaceimide E showed moderate activity to inhibit U937 cells. The preliminary structure-activity relationship was discussed.