Search

Six new macrolides named myrothecines D-G (1-4), 16-hydroxymytoxin B (5), and 14'-dehydrovertisporin (6), including four 10,13-cyclotrichothecane derivatives, in addition to 12 known compounds (7-18), were isolated from three endophytic Myrothecium roridum, IFB-E008, IFB-E009, and IFB-E012. The isolated compounds were characterized by MS, NMR, CD, and single-crystal X-ray crystallography. The isolated macrolides exhibited an antiproliferation effect against chronic myeloid leukemia K562 and colorectal carcinoma SW1116 cell lines. Compounds 1-6 were cytotoxic, with IC50 values ranging between 56 nM and 16 μM. Since slight structural changes led to obvious activity differences, the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were then used to explore the 3D QSAR (three-dimensional quantitative structure-activity relationship) of these macrolides. The result showed that the steric, electrostatic, hydrophobic, and H-bond acceptor factors were involved in their cytotoxicity and provided an in-depth understanding of the structure-activity relationships of these metabolites.

Residual dipolar couplings (RDCs) have attracted attention in light of their great impact on the structural elucidation of organic molecules. However, the effectiveness of RDC measurements is limited by the shortage of alignment media compatible with widely used organic solvents, such as DMSO. Herein, we present the first liquid crystal (LC) based alignment medium that is compatible with pure DMSO, thus enabling RDC measurements of polar and intermediate polarity molecules. The liquid crystals were obtained by grafting polymer brushes onto graphene oxide (GO) using free radical polymerization. The resulting new medium offers several advantages, such as absence of background signals, narrow line shapes, and tunable alignment. Importantly, this medium is compatible with π-conjugated molecules. Moreover, sonication-induced fragmentation can reduce the size of GO sheets. The resulting anisotropic medium has moderate alignment strength, which is a prerequisite for an accurate RDC measurement.

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.

A phytochemical study of Hopea hainanensis has led to the isolation of three new polyphenols and one known compound. The most important of these compounds are hopeahainols A (2) and B (3), which contain an unprecedented carbon skeleton. The structures were elucidated by analysis of the spectroscopic data including single-crystal X-ray spectroscopy and computational methods. Hopeahainol A was an acetylcholinesterase inhibitor with an IC50 value of 4.33 microM, which is comparable to that of huperzine A, a presently prescribed drug for the treatment of Alzheimer, while other similar structures were inactive. This observation was complemented by a 3D interaction model of the inhibitor with active sites.

Three new polyketides, named daldinone F (1), nodulisporin G (2), and dalmanol C (3), together with five known compounds, 4-8, were isolated from cultures of Daldinia eschscholzii. The structures of the new compounds were elucidated by extensive NMR and MS analyses. Compound 1 showed moderate cytotoxic activity against SW480 cancer cells with an IC50 value of 9.59 μM, and its absolute configuration was determined by single crystal X-ray diffraction.

Using 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum(II) (cisplatin, CDDP) as starting compounds, 5-FU-cisplatin adducts cis-[Pt(NH(3))(2)(HFU)Cl] (1) and cis-[Pt(NH(3))(2)(HFU)(2)] (2) were prepared. The obtained complexes were characterized by IR, ES-MS and 1H NMR spectroscopy. Complex 1 reacted with guanosine-5'-monophosphate (5'-GMP) and gave rise to a stable mixed-ligand complex cis-[Pt(NH(3))(2)(HFU)(GMP)] (3), whereas 2 did not undergo a similar reaction. In vitro cell growth inhibition tests of complexes 1 and 2 exhibited moderate antitumor activities against the melanoma B16-BL6 cell line. This work provides the basis for a potential alternative for the combinational use of 5-FU and CDDP in cancer therapy.

Residual dipolar couplings (RDCs) have proven to be an invaluable anisotropic NMR parameter for the structural elucidation of complex biopolymers and organic molecules. However, a remaining bottleneck limiting its wider use by organic and natural product chemists is the lack of a range of easily applicable aligning media for diverse organic solvents. In this study, graphene oxide (GO) liquid crystals (LCs) were developed to induce partial orientation of organic molecules to allow RDC measurements. These LCs were determined to be maintainable at very low concentrations (as low as 1 mg/mL, corresponding to quadrupolar (2)H splittings ranging from 2.8 to 30 Hz and maximum (13)C-(1)H dipolar couplings of 20 Hz for camphor in a CH3COCH3/water system) and to be remarkably stable and broadly compatible with aqueous and organic solvents such as dimethyl sulfoxide, CH3COCH3, and CH3CN. Moreover, compared with those for other alignment media, very clean and high-quality NMR spectra were acquired with the GO molecules in solution because of their rigidity and high molecular weight. The developed medium offers a versatile and robust method for RDC measurements that may routinize the RDC-based structure determination of organic molecules.

The cadmium complexes with the formulae CdLX2·nH2O (X = Cl−, n = 1; X = NO−3, n = 0.5), Cd(L-H)LX (X = ClO−4, BF−4) and Cd(L-H)Ac, where L is 2,6-bis(benzimidazol-2′-yl)pyridine, were obtained by reactions of L with different cadmium salts in methanol and characterized by elemental analysis, electrical conductance, IR and 1H NMR spectra. It has been found also that in the perchlorate, acetate and tetrafluoroborate complexes the ligand loses an N-proton on the benzimidazole ring of the ligand, acting as a singly negative ligand. The neutral complex (Cd(L-H)2 was also first structurally characterized. The geometry about cadmium is a distorted octahedron with six nitrogen atoms from two singly negative tridentate ligands.

Two new compounds, named 2-formylpyrrole-4-acrylamide (1) and dihydrostreptazolin (2) were isolated from the fermentation broth of BY-4, an actinomycetes residing in the gut of Odontotermes formosanus. The structures of 1 and 2 were elucidated by extensive spectral analysis (1H, 13C, 2D NMR, and HRESIMS). The isolated compounds were assayed for cytotoxic and antimicrobial activities.

The chemical investigation of Artemisia cf. dolosa afforded several known compounds as well as 10 new p -coumaric acid derivatives. The structures were elucidated by high field NMR techniques.

Along with the known secondary metabolites lumichrome, physcion, and emodin-1,6-dimethyl ether, three alkaloids named penicidones A-C (1-3) were isolated from the culture of Penicillium sp. IFB-E022, an endophytic fungal strain residing in the stem of Quercus variabilis (Fagaceae). The structures of penicidones A-C were established by a correlative interpretation of spectroscopic data including IR, UV and HR-ESI-MS, as well as by analysis of a set of 1D and 2D NMR experiments. The stereochemistry of compounds 1 and 2 was obtained by comparison of the optical rotation with those of vermistatin and its analogues. Penicidones A-C were the first group of natural products possessing a penicidone framework. Compounds 1-3 exhibited moderate cytotoxicity against four cancer cell lines.

A new oxoaporphine alkaloid, sinofranine, was isolated from the stem of Sinofranchetia chinensis. The structure of the new alkaloid was elucidated by a combination of spectral methods (IR, MS, 1H and 13C-NMR, NOED and COSY).

The polar fractions of Artemisia rutifolia afforded three new guaianolides, a germacranolide and a trihydroxycostic acid methyl ester. Structures were elucidated by high field NMR techniques.