Charminarone,a seco-pseudoguaianolide from Parthenium hysterophorus

A novel sesquiterpenoid, charminarone, the first seco-pseudoguaianolide, has been isolated along with several known compounds from the whole plant of Parthenium hysterophorus. The structure of the new compound has been settled as 1,10-seco-dihydroisoparthenin 1,10-dione from its spectral data as well as from its conversion by reductive coupling reaction with Zn/TiCl(4) reagent to the known compound, anhydrodihydroisoparthenin. The reagent Zn/TiCl(4) has been used here for the first time to construct the seven membered ring of a pseudoguaianolide sesquiterpenoid.     

A modified version of fluctuating asymmetry, potential for the analysis of Aesculus hippocastanum L. compound leaves

My research interest was to create a new, simple and tractable mathematical framework for analyzing fluctuating asymmetry (FA) in Aesculus hippocastanum L. palmately compound leaves (each compound leaf with 7 obviate, serrate leaflets). FA, being random differences in the development of both sides of a bilaterally symmetrical character, has been proposed as an indicator of environmental and genetic stress. In the present paper the well-established Palmer's procedure for FA has been modified to improve the suitability of the chosen index (FA1) to be used in compound leaf asymmetry analysis. The processing steps are described in detail, allowing us to apply these modifications for the other Palmer's indices of FA as well as for the compound leaves of other plant species.     

一种植物生长激素-N'-(5-硝基-2-羟基苯亚甲基)-3,5-二羟基苯甲酰肼的合成、晶体结构和抗菌活性

目的:合成并表征一种属于植物生长激素的席夫碱类化合物.方法:由5-硝基水杨醛和3,5-二羟基苯甲酰肼在甲醇溶液中反应得到N′-(5-硝基-2-羟基苯亚甲基)-3,5-二羟基苯甲酰肼.结果:用单晶X-射线衍射法测得其结构并表征,同时通过抗菌实验证明其在一定浓度下具有明显的抗菌活性.结论:这种席夫碱类化合物在某种程度上具有明显的抗菌活性.     

Crystallization of a derivative of a new coenzyme,methoxatin

A new compound, derived from a parent compound to which we have given the trivial name, methoxatin, has been isolated from a methanol-oxidizing bacterium, and crystallized. Its chemical structure was determined by X-ray crystallography. Methoxatin is implicated as a coenzyme in the oxidation of substrate alcohols. This report describes the purification and crystallization of the derivative, acetonyl methoxatin.     

Solid-phase combinatorial synthesis using MicroKan reactors, Rf tagging, and directed sorting

A modular system for high-output solid-phase combinatorial synthesis has been designed and developed. The system employs three technological innovations to achieve its high efficiency and reliability: (1) application of microreactors as the reaction units in solid-phase synthesis; (2) use of radiofrequency tagging as the non-chemical tracking method; and (3) development of the directed sorting technology for split & pool synthesis. The system has been successfully applied in the synthesis of compound libraries of several hundred to several thousand compounds in multi-milligrams per compound quantity by many organizations.     

Toward novel HIV-1 integrase binding inhibitors: molecular modeling, synthesis, and biological studies

The identification of a novel hit compound as integrase binding inhibitor has been accomplished by means of virtual screening techniques. A small family of structurally related molecules has been synthesized and biologically evaluated with one of the compounds showing an IC(50)=12 microM.     

Synthesis of 5-S-L-cysteinyl-glycine-L-dopa, a natural substrate for serum and melanocyte dipeptidase

A method for synthesis of the phaeomelanin pigment intermediate compound 5-S-L-cysteinyl-glycine-L-dopa is presented. This thioether has been suggested as a precursor to 5-S-L-cysteinyl-L-dopa, the key intermediate compound in phaeomelanin pigment formation. 5-S-Glutathione-L-dopa is first synthesized by the tyrosinase-catalyzed reaction between L-dopa and glutathione. The 5-S-glutathione-L-dopa is then converted to 5-S-L-cysteinyl-glycine-L-dopa using the enzyme gamma-glutamyl transpeptidase. The compound thus obtained was suitable as a substrate for melanoma cell and serum dipeptidase which converts the compound into 5-S-L-cysteinyl-L-dopa and glycine. The optimum pH for the dipeptidase from melanoma cells was 7.5 and the Km was 1.2 mM.     

Structure of euhalothece-362, a novel red-shifted mycosporine-like amino acid, from a halophilic cyanobacterium (Euhalothece sp.)

The unicellular cyanobacterium Euhalothece sp. strain LK-1, isolated from a gypsum crust on the bottom of a hypersaline saltern pond in Eilat, Israel, contains high concentrations of two mycosporine-like amino acids with maximum absorbance at 331 and 362 nm when grown at high light intensities. The 331 nm-absorbing compound has previously been identified as mycosporine-2-glycine. Here, we confirm this identification and document the elucidation of the structure of the 362 nm absorbing compound ('euhalothece-362'), using liquid chromatography/mass spectrometry combined with other techniques, as a novel compound, 2-(E)-3-(E)-2,3-dihydroxyprop-1-enylimino-mycosporine-alanine.     

Glycozolidol,an antibacterial carbazole alkaloid from Glycosmis pentaphylla

Glycozolidol, a new carbazole alkaloid, has been isolated from the roots of Glycosmis pentaphylla. Its structure has been established as 6-hydroxy-2-methoxy-3-methylcarbazole on the basis of physical and chemical evidence. The compound has been found to be active at some Gram-positive and Gram-negative bacteria.     

Glycolone,a quinolone alkaloid from Glycosmis pentaphylla

Glycolone, a quinolone alkaloid has been isolated from the leaves of Glycosmis pentaphylla. The structure of the compound has been established as 4,8-dimethoxy-3-(3-methyl but-2-enyl)-2-quinolone from physical and chemical evidences.     

Synthesis of methyl (5S,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-7,9,11,13-hexadecatetraenoate,an analogue of 15R-lipoxin A4

We describe a method for the synthesis of methyl (5S,6R,7E,9E,11Z,13E,15S)-16-(4-fluorophenoxy)-5,6,15-trihydroxy-7,9,11,13-hexadecatetraenoate, a compound that has been described as a metabolically stable analogue of 15R-lipoxin A(4).     

Preparation,structure, and properties of periodate-oxidised ATP,a potential affinity-labelling reagent

(1) Periodate oxidation of ATP yields a single product which has been purified and characterised. Periodate-oxidised ATP (o-ATP) behaves as a single compound during TLC analysis, but NMR spectral studies show that it exists in aqueous solution as an equilibrium mixture of three dialdehyde monohydrates and a dihydrate. Little free aldehyde is present. The dialdehyde monohydrates are in the form of diastereomeric cyclic hemiacetals. (2) The dialdehyde grouping of o-ATP can be reduced with sodium borohydride, producing a dialcohol. (3) o-ATP has been frequently used in attempts to affinity label nucleotide-binding sites on proteins. The proposed structure of o-ATP is discussed in relation to this use for o-ATP.     

Design,synthesis, screening,and molecular modeling study of a new series of ROS1 receptor tyrosine kinase inhibitors

A series of rationally designed ROS1 tyrosine kinase inhibitors was synthesized and screened. Compound 12b has showed good potency with IC₅₀ value of 209 nM, which is comparable with that of the reference lead compound 1. Molecular modeling studies have been performed, that is, a homology model for ROS1 was built, and the screened inhibitors were docked into its major identified binding site. The docked poses along with the activity data have revealed a group of the essential features for activity. Overall, simplification of the lead compound 1 into compound 12b has maintained the activity, while facilitated the synthetic advantages. A molecular interaction model for ROS1 kinase and inhibitors has been proposed.     

Isolation of Zeanic Acid,a Natural Plant Growth-regulator from Corn Steep Liquor and Its Chemical Structure

Corn steep liquor markedly inhibited the growth of the grass, alfalfa, as previously reported. The active principles from corn steep liquor were isolated. From the acidic fraction of corn steep liquor, white needles and yellow needles were isolated. The compound of white needles, which inhibited the germination of alfalfa seeds at the concentrations above 500 ppm, was found to be identical with ferulic acid known as germination inhibitor of plant seeds. The compound of yellow needles did not inhibit the germination of alfalfa seeds, but stimulated the growth of the plant. It has a structure related to β-acid which has been isolated from rice-bran and has been identified as 2,6-dihydroxycinchoninic acid. This active substance is a new quinoline, 2,8-dihydroxycinchoninic acid and was named zeanic acid.     

Preparation and initial characterization of the compound I, II, and III states of iron methylchlorin-reconstituted horseradish peroxidase and myoglobin: models for key intermediates in iron chlorin enzymes

To better understand the spectral properties of high valent and oxyferrous states in naturally occurring iron chlorin-containing proteins, we have prepared the oxoferryl compound I derivative of iron methylchlorin-reconstituted horseradish peroxidase (MeChl-HRP) and the compound II and oxyferrous compound III states of iron MeChl-reconstituted myoglobin. Initial spectral characterization has been carried out with UV-visible absorption and magnetic circular dichroism. In addition, the peroxidase activity of iron MeChl-HRP in pyrogallol oxidation has been found to be 40% of the rate for native HRP. Previous studies of oxoferryl chlorins have employed tetraphenylchlorins in organic solvents at low temperatures; stable oxyferrous chlorins have not been previously examined. The present study describes the compound I, II, and III states of histidine-ligated iron chlorins in a protein environment for the first time.     

Synthesis, hydrolysis and anti-EBV activity of a series of 3'-modified cycloSal-BVDUMP pronucleotides

A series of cycloSal-BVDUMP phosphate triesters has been prepared. The prototype compound was 3-methyl-cycloSal-BVDUMP 2. Furthermore, a series of 3'-O-acyl-modified derivatives having carboxylic acids with different lipophilicity or a L-configurated alpha-amino acid (phenylalanine) was prepared. The hydrolysis properties in phosphate buffer PBS as well as in PBS containing pig liver esterase (PLE) will be described. Finally, the biological activity against EBV has been determined.     

Structure of Helicobacter pylori catalase, with and without formic acid bound, at 1.6 A resolution

Helicobacter pylori produces one monofunctional catalase, encoded by katA (hp0875). The crystal structure of H. pylori catalase (HPC) has been determined and refined at 1.6 A with crystallographic agreement factors R and R(free) of 17.4 and 21.9%, respectively. The crystal exhibits P2(1)2(1)2 space group symmetry and contains two protein subunits in the asymmetric unit. The core structure of the HPC subunit, including the disposition of a heme b prosthetic group, is closely related to those of other catalases, although it appears to be the only clade III catalase that has been characterized that does not bind NADPH. The heme iron in one subunit of the native enzyme appears to be covalently modified, possibly with a perhydroxy or dioxygen group in a compound III-like structure. Formic acid is known to bind in the active site of catalases, promoting the breakdown of reaction intermediates compound I and compound II. The structure of an HPC crystal soaked with sodium formate at pH 5.6 has also been determined to 1.6 A (with R and R(free) values of 18.1 and 20.7%, respectively), revealing at least 36 separate formate or formic acid residues in the HPC dimer. In turn, the number of water molecules refined into the models decreased from 1016 in the native enzyme to 938 in the formate-treated enzyme. Extra density, interpreted as azide, is found in a location of both structures that involves interaction with all four subunits in the tetramer. Electron paramagnetic resonance spectra confirm that azide does not bind as a ligand of the iron and that formate does bind in the heme pocket. The stability of the formate or formic acid molecule found inside the heme distal pocket has been investigated by calculations based on density functional theory.     

Rhoiptelenol and rhoiptelenone, two pentacyclic triterpenes from Sideritis macrostachya

The pentacyclic triterpenes rhoiptelenol and rhoiptelenone have been isolated from Sideritis macrostachya. Rhoiptelenone is a new natural compound, whose structure has been determined as D:B-friedo-urs-5-en-3-one. The 1H and 13C NMR spectra of rhoiptelenol, rhoiptelenol acetate and glutinol have been reassigned. The natural occurrence of the D:B-friedo-ursene and D:B-friedo-oleanene derivatives has been examined.     

The production of a phytotoxin,nectrolide, by some root-surface isolates ofCylindrocarpon radicicola,Wr.

Summary A phytotoxic compound, for which the name nectrolide has been proposed, was isolated fromCylindrocarpon radicicola. Analysis of nectrolide and its physical and chemical properties show that the compound is identical with brefeldin A, an antibiotic produced byPenicillium brefeldianum.Twenty different isolates ofC. radicicola from plant roots were examined for their ability to produce nectrolide in liquid culture. Twelve of these yielded nectrolide at concentrations varying from 31 to 82 µg per ml when grown for 14 days on Czapek-Dox liquid medium. Eight isolates did not yield the metabolite in culture.At a concentration of 6 µg per ml nectrolide arrested the growth of germinated blackbutt seedlings, whilst at lower concentrations (2–4 µg per ml) the compound caused severe stunting and blackening of the roots of seedling plants. Nectrolide watered onto blackbutt seedlings growing in forest soils can be detected in the roots after 24 hrs. The compound has been crystallised from ether extracts of tomato roots supplied with pure nectrolide and can be detected in stem tissues within 24 hours of watering it onto the roots.As a result of the widespread association ofC. radicicola with unthrifty plants and the phytotoxic nature of nectrolide, it is suggested that this compound may function in a number of plant diseases, the causes of which have not been elucidated.     

Ravesilone,a quinolone alkaloid from Ravenia spectabilis

A new quinolone alkaloid designated ravesilone has been isolated from the leaves of Ravenia spectabilis. From spectral evidence the structure of the compound has been established as 3,4,5,6-tetrahydro-7-hydroxy-2,2,6-trimethyl-5-oxo-2H-pyrano[3,2-c]quinoline.