Inhibition effects of gangliosides G(M1), G(D1a) and G(T1b) on base-catalyzed isomerization of prostaglandin A(2)

Micellar inhibition effect of gangliosides on a degradation of drug was investigated, where ganglioside G(M1) (GM1), G(D1a) (GD1a) and G(T1b) (GTlb) whose sialic acid residue is one, two and three, respectively, were used. The base-catalyzed isomerization of prostaglandin A(2) (PGA(2)) to prostaglandin B(2) (PGB(2)) was chosen as a model experiment. The rate for the isomerization of PGA(2) was determined by measuring the concentration of PGA(2) (and PGB(2)) with a high-performance liquid chromatography. Gangliosides micelles inhibited the isomerization of PGA(2). The inhibition effect of GT1b micelles was larger than that of GD1a micelles. This result would be due to the larger absolute value of surface potential of GT1b micelles, which brings about a larger electrostatic repulsion between micellar surface and OH(-). The terminal sialic acid residue of ganglioside was effective to inhibit the isomerization of PGA(2). GM1 micelles without terminal sialic acid residue but with large aggregation number exhibited a superior steric shielding effect rather than an electrostatically repulsive effect. The inhibition effect of GM1 micelles was enhanced by the mixed micellization with the other ganglioside with a terminal sialic acid residue. GM1-GD1a or GM1-GT1b mixed micelles remarkably inhibited the isomerization of PGA(2). The physiological activity of PGs in the biological membranes containing gangliosides was also discussed.     

Beilschmiedic Acids F and G,Further Endiandric Acid Derivatives from Beilschmiedia anacardioides

Two new endiandric acid derivatives, beilschmiedic acid F ( 1 ) and beilschmiedic acid G ( 2 ), together with three known constituents, beilschmiedic acid A, beilschmiedic acid C, and sitosterol 3‐β‐D ‐glucopyranoside, were isolated from the stem bark of Beilschmiedia anacardioides. Their structures were elucidated mainly by using a combination of 1D‐ and 2D‐NMR techniques. The structure and relative configuration of beilschmiedic acid G ( 2 ) was also confirmed by X‐ray crystallographic analysis.     

等电子-等自旋与非等旋反应的G2(MP2)和G2研究

我们在前文［1－2］中分别用MP2－4／6－31G**／／MP2／6－31G**及MP4／6－311G（2df，Zpd）／／MP2／6－31G**研究了一些双原子氢化物、卤化物、硫化物和氧化物的化学反应的烂变·这些化学反应按如下类型分为四组，即（1）反应物与生成物之间为等电子一等自旋关系，（2）价层等电一等旅，（3）等施和（4）非等旅·结果表明，MP4／6－3fiG（2才，ZPd）对于（1），（2）和（3）类反应，基本上与实验误差小于士15kJ·mo－‘而对非等旋反应仍有较大误差；MPZ－4／6－31G””只对（1）类反应较好．由于PoPle等人近几年来创立的Gaussi…     

Poecillastrin E,F, and G,cytotoxic chondropsin-type macrolides from a marine sponge Poecillastra sp.

Poecillastrin E (1), F (2), and G (3) were isolated from a marine sponge Poecillastra sp. as the cytotoxic constituents. Their planar structures were determined by analyzing the MS and NMR spectra. They are closely related to the known poecillastrin C (4). The absolute configuration of the β-hydroxyaspartic acid (OHAsp) residue was determined to be D-threo by Marfey's analysis of the hydrolysate. The mode of lactone ring formation of OHAsp residue in 1–3 was determined by selective reduction of the ester linkage followed by acid hydrolysis.     

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP

The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC–ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.     

Rubesanolides F and G: Two Novel Lactone-Type Norditerpenoids from Isodon rubescens

A phytochemical investigation of the leaves of the medicinal plant Isodon rubescens led to the isolation of the two new degraded abietane lactone diterpenoids rubesanolides F (1) and G (2). Their structures were elucidated based on the analyses of the HRESIMS and 1D/2D NMR spectral data, and their absolute configurations were determined by ECD spectrum calculations and X-ray single crystal diffraction methods. Compounds 1 and 2, with a unique γ-lactone subgroup between C-8 and C-20, were found to form a carbonyl carbon at C-13 by removal of the isopropyl group in an abietane diterpene skeleton. Rubesanolide G (2) is a rare case of abietane that possesses a cis-fused configuration between rings B and C. The two isolates were evaluated for their biological activities against two cancer cell lines (A549 and HL60), three fungal strains (Candida alba, Aspergillus niger and Rhizopus nigricans) and three bacterial strains (Escherichia coli, Staphylococcus aureus and Bacillus subtilis).     

A new polyketide purpurogenic acid: the activated production of polyketides by the diethyl sulphate mutagenesis of marine-derived Penicillium purpurogenum G59

A new polyketide, purpurogenic acid (1), and two known polyketides, (-)-mitorubrin (2) and (-)-mitorubrinol (3), were isolated from a fungal mutant derived from the diethyl sulphate (DES) mutagenesis of marine-derived Penicillium purpurogenum G59. The planar structure of new 1 was elucidated by spectroscopic methods and the absolute configuration was assigned on the basis of [α]_D and CD data. In our preliminary MTT assay, 1 inhibited human cancer K562, HL-60, HeLa and BGC-823 cells with the inhibition rates of 52.7, 78.8, 38.4 and 35.3% at the 100 μg/mL, respectively.     

几种含芯电子相关能修正的G2和G2(ACI)方法

针对冻结芯电子近似,在MP2/6-311G(d,p)级别上对G2、MP2/6-311G(d)和MP2/6-311G(d,p)级别上对G2(QCI)方法进一步考虑了芯电子相关能修正,尝试建立了G2(fu2)、G2(QCI/ful)和G2(QCI/fu2)方法。G2-l test set 的反应能量计算结果表明,这些方法进一步减小了经验修正量;G2(QCI/ful)和G2(QCI/fu2)也比G2(QCI)的总体精度有所提高;但G2(fu2)在G2基础上,总体精度没有改善。G2(fu2)、G2(QCI/ful)和G2(QCI/fu2)计算G2-l test set反应能量的平均绝对偏差分别为5.11、4.74和4.81kJ mol-1,G2和G2(QCI)分别为5.09和4.97kJ mol-1.     

Total synthesis of buergerinin F and buergerinin G

Syntheses of buergerinin F (1) and buergerinin G (2) were carried out to establish the absolute stereochemistry of these natural products. A linear sequence was used to synthesize 1 in 15 steps and 9% overall yield from thymidine. Subsequent oxidation of 1 with ruthenium tetroxide afforded 2 in 77% yield.     

某些离解能、电子亲合能等的G2计算与评价

PoPle及其合作者创立的Gaussian再简称GZ）理论［‘－’］，以其相对可靠的化学精度和相应较小的计算量已经引起了实验和理论化学家们的广泛关注问．p。ple等人在他们的GZ文章中强调了GZ的理论计算结果在研究离解能等化学问题中与精确实验数据之间的偏差普遍不大于全8．狄J规厂‘．我们近期的研究表明＊’1，＊2和优（＊则在计算一般化学反应能量中，绝大多数情况下，分别都能保证结果与实验偏差在全8．4和士13kJ·mol‘以内．近年来，已有大量的研究工作表明，GZ的理论结果已广泛用于未知实验数据的预测、已有实验数据的评价和修正等…     

Nonpeptide inhibitors of cathepsin G: optimization of a novel beta-ketophosphonic acid lead by structure-based drug design

The serine protease cathepsin G (EC 3.4.21.20; Cat G), which is stored in the azurophilic granules of neutrophils (polymorphonuclear leukocytes) and released on degranulation, has been implicated in various pathological conditions associated with inflammation. By employing high-throughput screening, we identified beta-ketophosphonic acid 1 as a moderate inhibitor of Cat G (IC(50) = 4.1 microM). We were fortunate to obtain a cocrystal of 1 with Cat G and solve its structure by X-ray crystallography (3.5 A). Structural details from the X-ray analysis of 1.Cat G served as a platform for optimization of this lead compound by structure-based drug design. With the aid of molecular modeling, substituents were attached to the 3-position of the 2-naphthyl ring of 1, which occupies the S1 pocket of Cat G, to provide an extension into the hydrophobic S3 region. Thus, we arrived at analogue 7 with an 80-fold potency improvement over 1 (IC(50) = 53 nM). From these results, it is evident that the beta-ketophosphonic acid unit can form the basis for a novel class of serine protease inhibitors.     

Protonation of phenylboronic acid: Comparison of G3B3 and G2MP2 methods

G3B3 and G2MP2 calculations using Gaussian 03 have been carried out to investigate the protonation preferences for phenylboronic acid. All nine heavy atoms have been protonated in turn. With both methodologies, the two lowest protonation energies are obtained with the proton located either at the ipso carbon atom or at a hydroxyl oxygen atom. Within the G3B3 formalism, the lowest‐energy configuration by 4.3 kcal · mol^?1 is found when the proton is located at the ipso carbon, rather than at the electronegative oxygen atom. In the resulting structure, the phenyl ring has lost a significant amount of aromaticity. By contrast, calculations with G2MP2 show that protonation at the hydroxyl oxygen atom is favored by 7.7 kcal · mol^?1. Calculations using the polarizable continuum model (PCM) solvent method also give preference to protonation at the oxygen atom when water is used as the solvent. The preference for protonation at the ipso carbon found by the more accurate G3B3 method is unexpected and its implications in Suzuki coupling are discussed. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Chlorinated briarane-type diterpenoids from the gorgonian coral Ellisella robusta (Ellisellidae)

Four chlorinated metabolites featuring briarane carbon skeletons have been isolated from the gorgonian coral Ellisella robusta, which was collected off the coast of southern Taiwan: two new natural products, robustolides D (1) and E (2), and two known metabolites, robustolides F (3) and G (4). The structures of metabolites 1–4 were determined by spectroscopic methods, using 1D and 2D NMR in particular. The structures and absolute stereochemistry of robustolides D (1), F (3), and G (4) were directly established by X-ray diffraction analysis. Robustolide D (1) is the first metabolite of briarane-related natural products found to possess two halogen atoms.     

G3(QCI)模型化学方法

建立了非微扰外推模式下的几种G3(QCI)方法：G3(QCI/fu1)、G3(QCI/fu2)、G3(QCI/ful)//B3PW91和G3(QCI/fu2)//B3PW91.其中,电子能量用QCISD(T,FC)/G3large直接计算,芯电子相关能分别在MP2/6-31G(d)和MP2/6-31G(d,p)级别上计算,对125个G2-1 test set 的计算结果表明,总体精度与G3和G3 //B3LYP相当;平均绝对偏差分别为4.370、4.389、4.061和4.022kJ mol-1,相应G3和G3//B3LYP分别为4.27和4.05kJ mol-1.文章提出的方法排除了G3中外推办法的不确定因素,且更适用于非平衡几何构型体系能量的定量计算。     

Crystal structure and absolute configuration of guan-fu G base methyliodide

Guan-fu base G is a new alkaloid isolated from root tuber of Aconitum coreanum Le'vl Raipaics. Guan-fu base G methyliodide crystallizes in orthorhombic system, space group D4/2-P2₁2₁2₁, with dimensions: a = 16.87Å, b = 16.93Å, c = 10.09Å; Z = 4. The three dimensional data were collected on a Phillips PW-1100 four-circle diffractometer with Mo K_a radiation. The structure was solved by heavy-atom method and subsequently successive Fourier syntheses. The structure was refined by block-diagonal matrix least squares methods to R = 0.0578 for 2848 reflexions. The absolute configuration was determined by computation of the R factor for the two possible configurations using anomalous scattering of iodine.     

Characterisation of Taxlllaids A–G; Natural Products from Xenorhabdus indica

Six new lipodepsipeptides and an additional linear derivative named taxlllaids A–G ( 1 – 7 ) have been identified in the entomopathogenic bacterium Xenorhabdus indica. The structures of the main compounds have been solved by detailed NMR spectroscopic analysis and the structures of minor derivatives were elucidated by a combination of labelling experiments and detailed MS experiments. The absolute configuration of the taxlllaids was deduced by using the advanced Marfey method and analysis of the biosynthesis gene cluster showing the presence of epimerisation domains, which was subsequently proved to be correct by solid‐phase peptide synthesis of all taxlllaids. The exchange of a single amino acid in the adenylation domain was shown to be responsible for substrate promiscuity of the third A domain, resulting in the incorporation of leucine, phenylalanine or tyrosine. Bioactivity testing revealed the taxlllaids to be weakly active against Plasmodium falciparum and against a number of eukaryotic cell lines.     

First Stereoselective Total Synthesis of Gallicynoic Acids G and H

A stereoselective convergent total synthesis of two acetylenic acids, gallicynoic acid G ( 1 ) and H ( 2 ), is reported, involving asymmetric reduction of alkynones 3 and 4 , respectively, with the Corey? Bakshi? Sibata (CBS) catalyst as a key step (Scheme 3), 3 and 4 being obtained from a common intermediate, the chiral alkynol 12 (Scheme 2).     

Structure of cymbidine A, a monomeric peptidoglycan-related compound with hypotensive and diuretic activities, isolated from a higher plant, Cymbidium goeringii (Orchidaceae)

The structure of a new monomeric peptidoglycan-related compound with hypotensive and diuretic activities, cymbidine A (1) isolated from the orchid Cymbidium goeringii, was elucidated mainly by spectroscopic analysis. The structure of 1 was shown to involve four amino acids (D-alanin, meso-diaminopimelic acid, D-gultamic acid, and L-valine) and two amino sugars (N-acetylglucosamine and 1,6-anhydro-N-acetylmuramic acid). The sequence of the amino acids and amino sugars was determined by the analysis of 2D NMR data. The absolute stereochemistries of the three amino acids (D-Ala, D-Glu and L-Val) were determined by the modified Marfey's method, and the (6S,10R) configurations of meso-diaminopimelic acid in 1 were indicated on the basis of the CD analysis. The absolute stereochemistry of 1,6-anhydro-N-acetylmuramic acid was also determined by CD data.     

Tyromycic acids F and G: two new triterpenoids from the mushroom Tyromyces fissilis

Phytochemical examination of the methanol extract of the fruit bodies of the Japanese fungus Tyromyces fissilis led to the isolation of two new lanostane derivatives called tyromycic acids F (1) and G (2), together with two known compounds, tyromycic acid (3) and trametenolic acid B (4). Their structures were identified by 2D NMR, IR, and UV spectroscopy.