Chlorpromazine oligomer is a potentially active substance that inhibits human D-amino acid oxidase, product of a susceptibility gene for schizophrenia

D-amino acid oxidase (DAO), a potential risk factor for schizophrenia, has been proposed to be involved in the decreased glutamatergic neurotransmission in schizophrenia. Here we show the inhibitory effect of an antipsychotic drug, chlorpromazine, on human DAO, which is consistent with previous reports using porcine DAO, although human DAO was inhibited to a lesser degree (K(i) = 0.7 mM) than porcine DAO. Since chlorpromazine is known to induce phototoxic or photoallergic reactions and also to be transformed into various metabolites, we examined the effects of white light-irradiated chlorpromazine on the enzymatic activity. Analytical methods including high-resolution mass spectrometry revealed that irradiation triggered the oligomerization of chlorpromazine molecules. The oligomerized chlorpromazine showed a mixed type inhibition with inhibition constants of low micromolar range, indicative of enhanced inhibition. Taken together, these results suggest that oligomerized chlorpromazine could act as an active substance that might contribute to the therapeutic effects of this drug.

Journal of Enzyme Inhibition and Medicinal Chemistry


Isolation and Absolute Configuration Determination of Aliphatic Sulfates as the Daphnia Kairomones Inducing Morphological Defense of a Phytoplankton

2,6-Dimethylheptyl sulfate (1) and 6-methyloctyl sulfate (3) were isolated from Daphnia pulex as the Daphnia kairomones that induced morphological defense of a freshwater phytoplankton Scenedesmus gutwinskii var. heterospina (NIES-802). The absolute stereochemistry at C2 of 1 was determined by (1)H-NMR analysis of the (R)-MTPA ester of alcohol 2. The absolute configuration at C6 of 3 was determined by Ohrui's method applied to alcohol 4.


Aliphatic sulfates released from Daphnia induce morphological defense of phytoplankton: isolation and synthesis of kairomones


Anti-Helicobacter pylori Compounds from Santalum album

Six new sesquiterpenes, (Z)-2beta-hydroxy-14-hydro-beta-santalol (1), (Z)-2alpha-hydroxy-albumol (2), 2R-(Z)-campherene-2,13-diol (3), (Z)-campherene-2beta,13-diol (4), (Z)-7-hydroxynuciferol (5), and (Z)-1beta-hydroxy-2-hydrolanceol (6), together with five known compounds, (Z)-alpha-santalol (7), (Z)-beta-santalol (8), (Z)-lanceol (9), alpha-santaldiol (10), and beta-santaldiol (11), were isolated from Santalum album, by using bioassay-guided fractionation for Helicobacter pylori. The structures were determined by extensive NMR studies. The absolute configuration of compound 3 was determined by a modified Mosher method. The crude extracts as well as the isolated compounds showed antibacterial activity against H. pylori. Especially, compounds 7 and 8 have strong anti-H. pylori activities against a clarithromycin-resistant strain (TS281) as well as other strains.


9.4 T and 7.05 T Magnetic Fields Accelerate a Radical Oxidation Reaction with a Hypervalent (tert-Butylperoxy)iodane


1,3-Dipolar addition of nitrones to symmetrically substituted allenes: for the determination of absolute configuration of chiral allenes by NMR spectroscopy


Fucoxanthin and Its Metabolites in Edible Brown Algae Cultivated in Deep Seawater.


Fucoxanthin and Its Metabolites in Edible Brown Algae Cultivated in Deep Seawater


Inhibitory action of novel arginine derivative on catecholamine secretion evoked by acetylcholine from cultured bovine adrenal chromaffin cells

A novel product, 4-amino-5-guanidinopentanoic acid 15-[(4-aminobutyl)-3-aminopropylcarbamoyl] pentadecyl ester (Arg-HSA-Spm), was synthesized based on ptilomycalin A, which is one of the extracts from marine sponge. Arg-HSA-Spm contains arginine in its chemical structure. The pharmacological action of Arg-HSA-Spm on catecholamine secretion from cultured bovine adrenal chromaffin cells was examined. Arg-HSA-Spm inhibited catecholamine secretion stimulated by the physiological secretagog acetylcholine. This inhibitory action of Arg-HSA-Spm on catecholamine secretion induced by 10(-4) M acetylcholine was dose-dependent from 10(-8) M to 10(-5) M. In the presence of 3 x 10(-7) M Arg-HSA-Spm, the stimulation of catecholamine secretion observed by increasing acetylcholine up to 10(-3) M did not reach the maximal level observed without Arg-HSA-Spm. Arg-HSA-Spm at 10(-5) M suppressed both the increase in intracellular free Ca2+ level and the influx of 45Ca2+ induced by 10(-4) M acetylcholine. The Arg-HSA-Spm-induced suppression of intracellular free Ca2+ level, the influx of 45Ca2+ and catecholamine secretion were not observed in the presence of extracellular K+ at 56 mM. The results presented in this study suggested that Arg-HSA-Spm may inhibit the influx of extracellular Ca2+ into the cells, probably through its blocking action related to acetylcholine receptors, resulting in the inhibition of catecholamine secretion in adrenal chromaffin cells.


Resolution of 1- and 2-naphthylmethoxyacetic acids, NMR reagents for absolute configuration determination, by use of L-phenylalaninol

Racemic 1- and 2-naphthylmethoxyacetic acids (1NMA and 2NMA), the chiral anisotropic reagents used for absolute configuration determination of chiral secondary alcohols and primary amines, were conveniently resolved to enantiomers (>99% ee) by condensation with L-phenylalaninol (2-amino-3-phenylpropanol), chromatographic separation of the diastereomers, and hydrolysis. This method enables large-scale preparation of enantiomeric 1NMA and 2NMA.


Oxidation of Cyclopropane Terpenoids with Ruthenium Tetraoxide

Oxidation products of cyclopropanoid terpenes, (-)-carane (4), (+)-cyclosativene (5), laurinterol methyl ether (6), and thujopsane (7), with ruthenium tetraoxide were investigated.


Structures of the radical (DPPH) oxidation products of dihydrocapsaicin


Mechanism of potent antiperoxidative effect of capsaicin

The effect of a pungent ingredient of red pepper, capsaicin, on lipid peroxidation of rat liver mitochondria (RLM) induced by ADP/Fe(2+) was studied. Capsaicin inhibited the lipid peroxidation significantly, being more effective than the well-known antioxidant alpha-tocopherol. Capsaicin was also found to scavenge 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radicals both in solution and in membranes, especially the latter. Capsaicin was found to scavenge radicals both at/near the membrane surface and in the interior of the membrane. The phenolic OH-group of capsaicin remained intact after reaction with DPPH radicals, indicating that the hydroxyl group is not associated with the radical scavenging reaction. From the results of quantum chemical calculations of various radical intermediates derived from the model compound N-vanillylacetamide, and the findings that vanillin and 8-methyl-6-noneamide were major reaction products of capsaicin with DPPH radicals, it was concluded that the radical scavenging site of capsaicin is the C7-benzyl carbon.

Biochimica et Biophysica Acta (BBA) - General Subjects


Autoxidation of linoleic acid in a strong magnetic field (9.4 T)


Sesquiterpenes and Monoterpenes from the Bark of Inula macrophylla

Eleven new sesquiterpenes (1--11) and two thymol derivatives (12, 13), along with 12 known sesquiterpenes and monoterpenes, were isolated from the bark of Inula macrophylla. Their structures were determined on the basis of spectral evidence (especially by HREIMS and 2D NMR) as well as chemical transformations. The structure of macrophyllic acid A (1) was confirmed by X-ray analysis, and the absolute configuration of 1 was determined on the basis of the appropriate chemical conversions and the application of a modified Mosher's method.


Acceleration of Tributyltin Hydride Reduction of Phenethyl Iodide and m-Methoxybenzyl Bromide by a Strong Magnetic Field


A New Diterpene Dimer from the Bark of Chamaecyparis obtusa


Carbon-13 Spin-Lattice Relaxation Time (T1) for Assignment of Brominated Carbons


NMR Study of Acutanol, a New Cembrene Alcohol, and Sarcophytol A Isolated from the Soft coral Sarcophyton acutangulum


New Terpenoid Components from the Volatile Oils of the Soft Corals Clavularia viridis and Sarcophyton acutangulum

A new tetracyclic terpenoid hydrocarbon, cyclosinularane (1), and (+)-alloaromadendrene (2), the enantiomer of terrestrial (-)-alloaromadendrene, have been isolated from the volatile oil of the soft corals Clavularia viridis and Sarcophyton acutangulum, respectively. Their structures have been determined on the basis of NMR spectral analysis and their chiroptical properties.


Influence of the Conformation of Methoxy-(2-naphthyl)acetates (2NMA Esters) on Their Chemical Reactions

An SN2 reaction (NaI) of 1,7-di(methanesulfoxyl)heptadien-4-yl methoxy-(2-naphthyl)acetate and a tributyltin hydride reduction of 1,7-diiodo-4-yl methoxy-(2-naphthyl)acetate (2NMA) is crucial for determination of the absolute configuration of secondary alcohols.


The structures and absolute configurations of macrophyllic acids A E, five new rearranged eudesmane sesquiterpene acids from the bark of Inula macrophylla


Phenylglycine Methyl Ester, a Useful Tool for Absolute Configuration Determination of Various Chiral Carboxylic Acids

A new chiral anisotropic reagent, phenylglycine methyl ester (PGME), developed for the elucidation of the absolute configuration of chiral alpha,alpha-disubstituted acetic acids, has turned out to be applicable to other substituted carboxylic acids, such as chiral alpha-hydroxy-, alpha-alkoxy-, and alpha-acyloxy-alpha, alpha-disubstituted acetic acids, as well as to chiral beta, beta-disubstituted propionic acids. Because a carboxylic moiety is convertible from other functional groups, e.g., ozonolysis of an olefin and oxidative cleavage of a glycol, the present findings can expand the utility of the PGME method to the absolute configuration determination of various types of organic compounds, even those which initially lack oxygen functions. Several examples of the combination of chemical reactions and the PGME method are described.


Morinols A-L, twelve novel sesquineolignans and neolignans with a new carbon skeleton from morina chinensis


NMR Spectroscopic Determination of the Absolute Configuration of Chiral Sulfoxides via N-(Methoxyphenylacetyl)sulfoximines

Journal of the American Chemical Society


Sesterterpenoids and Diterpenoids of the Wax Excreted by a Scale Insect, Ceroplastes pseudoceriferus

A new sesterterpene, (2Z,6Z,10E)-cericerene-15,24-diol (1), and its 30-hydroxytriacontanoate (2) were isolated from the wax exuded by the scale insect Ceroplastes pseudoceriferus, together with the acetates and 30-hydroxytriacontanoates of 3,15-dihydroxy- and 15, 20-dihydroxylabda-7,13-diene (3-6). The absolute configurations of the labdadiene alcohols were antipodal to the ordinary labdanes isolated from terrestrial plants.


Chemical Study and Absolute Configuration of a New Marine Secospatane from the Brown Alga Dilophus okamurae

A new diterpene, dilkamural (1), of the secospatane class has been isolated from the brown alga Dilophus okamurae Dawson, and its structure, including absolute stereochemistry, has been determined by NMR spectroscopic and chemical means.


Application of the modified Mosher's method to linear 1,3-diols


Structure and Absolute Stereochemistry of Five New Secospatanes and a Spatane Isolated from the Brown Alga Dilophus okamurai Dawson


A Convenient One-pot Synthesis of Quaternary a-Methoxy-& a-Hydroxycarboxylic Acids


Determination of the absolute configuration of linear secondary alcohols adopting one enantiomer of the chiral anisotropic reagents, methoxy-(1-and 2-naphthyl)acetic acids


12-Lipoxygenase Inhibitory Activity of Japanese Seaweeds and Isolation of a Caulerpyne Derivative from the Green Alga Caulerpa taxifolia as an Inhibitor


Crenulacetal C, a Marine Diterpene, and Its Synthetic Mimics Inhibiting Polydora websterii, a Harmful Lugworm Damaging Peral Cultivation


A simple preparation of 17(R)-hydroxyeicosatetraenoic and eicosapentaenoic acids from the eicosanoylphloroglucinols, components of the brown alga, Zonaria diesingiana


Conformation of (S,S)-Methyl (2-Methyl-4-phenylbutanamido)(phenyl)acetate


Application of phenylglycine methyl ester (PGME) to determination of the absolute configuration of carboxylic acids having phenylalkyl group


Absolute Configurations of Some Hydroxy-fatty Acids Produced by the Insect Genus Laccifer

Bioscience, Biotechnology, and Biochemistry


Determination of the absolute configuration of yessotoxin, a polyether compound implicated in diarrhetic shellfish poisoning, by NMR spectroscopic method using a chiral anisotropic reagent, methoxy-(2-naphthyl)acetic acid


Absolute stereostructure of a 2,3,7,13-tetrahydroxyoctadecanoic acid, the framework of taurolipid B produced by a fresh-water protozoan, Tetrahymena thermophila


Ptilomycalin A, a novel Na+,K+- or Ca2+-ATPase inhibitor, competitively interacts with ATP at its binding site


2-Anthrylmethoxyacetic acid, a new chiral anisotropic reagent for elucidating the absolute configuration of acyclic alcohols


Antioxidant Activities of Macroalgal Components


Absolute Stereochemistry of Tanabalin an Insect Antifeedant Clerodane from Tanacetum balsamita


Dhydrokaempferol Glucoside from Cotyledons Promotes Flowering in Pharbitis nil


New chiral anisotropic reagents for determining the absolute configuration of carboxylic acids


Cryptoacetalide and Epicryptoacetalide, Novel Spirolactone Diterpenoids from Salvia miltiorrhiza


Turbinaric Acid, a Cytotoxic Secosqualene Carboxylic Acid from the Brown Alga Turbinaria ornata

A moderately cytotoxic secosqualene carboxylic acid designated turbinaric acid [1] has been isolated from the brown alga Turbinaria ornata, and it has been identified to be 4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenoic acid by means of spectral analysis and synthesis.


α-トコフェロールの立体異性体の分離および微量定量

α-トコフェロールの立体異性体の分離および微量定量