Cordiachromes from Auxemma oncocalyx

Further cordiachromes, rel-10,11β-epoxy-11-ethoxy-8-hydroxy-2-methoxy-8aβ-methyl-5,6,7,8,8a,9,10aβ-octahydro-1,4-anthracendione, 6-formyl-2-methoxy-9-methyl-7,8-dihydro-1,4-phenanthrendione, rel-8,11;9,11-diepoxy-1,4-dihydroxy-2-methoxy-8aβ-methyl-5,6,7,8,8a,9,10,10aβ-octahydro-10-anthracenone, rel-9,11-epoxy-1,4,8-trihydroxy-2-methoxy-8aβ-methyl-5,6,7,8,8a,9,10,10aβ-octahydro-10-anthracenone, rel-2″-methoxy-7″-methyl-1″,4″-naphtalendione-(6″→5)-tetrahydropyran-(2-eq→O→2ax)-tetrahydropyran-(5′→6)- 2-methoxy-7-methyl-1,4-naphthalendione, together with the known, allantoin, sitosterol and 3β-O-d-glucopyranosylsitosterol, have been isolated from Auxemma oncocalyx. Their structures were determined from spectral data, including 2D NMR experiments.     

Further phloroglucinol derivatives in the fruits of Mallotus japonicus

Two new rottlerin-like phloroglucinol derivatives were detected from the fruits of Mallotus japonicus and identified as 3-(3,3-dimethylallyl)-5-(3-acetyl-2,4-dihydroxy-5-methyl-6-methoxybenzyl)-phlorobutyrophenone and -phloroisobutyrophenone by spectral studies. 2,6-Dihydroxy-3-methyl-4-methoxyacetophenone was also isolated     

滑桃树内生真菌Fusarium sp.1RGa-1b中萘醌类代谢产物及其抗菌活性研究

从滑桃树内生真菌Fusarium sp．（1RGa—1b）的发酵代谢产物中分离得到6个一系列的萘醌类色素化合物,通过波谱分析将其结构鉴定为：3-methylether-fusarubin（1）,anhydrofusarubin（2）,2-aeetonyl-3-methyl-5-hydro—gen-7-methoxy—naphthazarin（3）,2-acetonyl-3-methyl-7-methoxy-8-hydrogen—naphthazarin（4）,2-acetonyl-3-methyl-7-methoxy—naphthazarin（5）,2-isopropanol-3-methyl-7-methoxy-naphthazafin（6）。利用纸片扩散法对这些化合物的抗细菌及抗真菌活性进行了初步测试,实验结果表明：化合物3和4具有弱的抗金黄色葡萄球菌的活性。     

广藿香大极性化学成分的研究

从广藿香(Pogostemon cablin (Blance)Benth.)地上部分乙醇提取物的正丁醇萃取部位分离得到13个化合物.通过光谱和波谱分析,分别鉴定为:芹菜素(1)、3,5,4'-三羟基-7-甲氧基黄酮(2)、3,5-二羟基_4',7-二甲氧基黄酮(3)、Apigenin 7-galacturonide(4)、Apigenin 7-(O-methylghacuronide)(5),Luteolin 7-O-(6-O-methyl-β-D-glucuronopyranoside)(6),4',5-二羟基-3',7-二甲氧基二氢黄酮(7)、Quercetha-7-β-D-ghcoside(8),3,23-Dihydroxy-12-oleanen-28-oic acid(9)、Syringaresinol-β-D-glucoside(10),毛蕊花糖苷(11)、列当苷(12)、紫葳新苷(13),化合物2～13均为首次从该植物中分离得到.     

Synthesis of the Stereoisomeric Mixture of the Compound Having the Proposed Structure for “Auxin b Lactone”

The composed having the proposed structure for auxin b lactone (XVIII) was synthesized by formic acid hydrolysis of 4-ethoxy-6-(3,5-di-sec-butyl-1-cyclopenten-1-yl)-5,6-dihydro-2-pyrone (XVII) which was, in turn, prepared by the Reformatsky reaction of 3,5-di-sec-butyl-1-cyclopentenealdehyde (XVI) with ethyl γ-bromo-β-ethoxycrotonate.     

Synthesis of C-glycopyranosylfuran derivatives by reaction of dialdehydes with cyanoacetamide

The reaction of diglycol- and thiodiglycol-aldehyde (1a,b) with cyanoacetamide yields cis-3,5-diacetoxy-4-carbamoyl-4-cyano-tetrahydropyran (2a) and -tetrahydrothiopyran (2b). When this reaction is applied to (2S)-2-(3-ethoxycarbonyl-2-methyl-5-furyl)-3,5-dihydroxy-1,4-dioxane (1c), (2S)-3,5-dihydroxy-2-(3-methoxycarbonyl-2-methyl-5-furyl)-1,4-dioxane (1d), and (2S,3R,5S)-2-(3-acetyl-2-methyl-5-furyl)-3,5-dihydroxy-1,4-dioxane (1e), 5-(3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-ethoxycarbonyl-2-methylfuran (2c), 5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-methoxycarbonyl-2-methylfuran (2e), and 3-acetyl-5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-2-methylfuran (2f), respectively, are formed with (4S,5S)-4-carbamoyl-4-cyano-2-(3-ethoxycarbonyl-2-methyl-5-furyl)-5-hydroxy-5,6-dihydropyran (3a) and (4S,5S)-4-carbamoyl-4-cyano-5-hydroxy-2-(3-methoxycarbonyl-2-methyl-5-furyl)-5,6-dihydropyran (3b) as minor products. The dehydration of 2a,b, 5-(2,4-di-O-acetyl-3-carbamoyl-3-cyano-3-deoxy-β-d-xylo-pentopyranosyl)-3-ethoxycarbonyl-2-methylfuran (2d), 2e, and 2f yields cis-3,5-diacetoxy-4,4-dicyano-tetrahydropyran and -tetrahydrothiopyran (2l,m), and the 5-(2,4-di-O-acetyl-3,3-dicyano-3-deoxy-β-d-erythro-pentopyranosyl) derivatives (2n–p) of 3-ethoxycarbonyl-2-methylfuran, 3-methoxycarbonyl-2-methylfuran, and 3-acetyl-2-methylfuran, respectively.     

Arylglycerol-γ-Formyl Ester as an Aromatic Ring Cleavage Product of Nonphenolic β-O-4 Lignin Substructure Model Compounds Degraded by Coriolus versicolor

4-Ethoxy-3-methoxyphenylglycerol-γ-formyl ester (compound IV) was identified as a degradation product of both 4-ethoxy-3-methoxyphenylglycerol-β-syringaldehyde ether (compound I) and 4-ethoxy-3-methoxyphenylglycerol-β-2,6-dimethoxyphenyl ether (compound II) by a ligninolytic culture of Coriolus versicolor. An isotopic experiment with a ¹³C-labeled compound (compound II′) indicated that the formyl group of compound IV was derived from the β-phenoxyl group of β-O-4 dimer as an aromatic ring cleavage fragment. However, compound IV was not formed from 4-ethoxy-3-methoxyphenylglycerol-β-guaiacyl ether (compound III). γ-Formyl arylglycerol (compound IV) could be a precursor of 4-ethoxy-3-methoxyphenylglycerol (compound VI), because 3-(4-ethoxy-3-methoxyphenyl)-1-formyloxy propane (compound VII) was cleaved to give 3-(4-ethoxy-3-methoxyphenyl)-1-propanol (compound VIII) by C. versicolor. 4-Ethoxy-3-methoxyphenylglycerol-β,γ-cyclic carbonate (compound V), previously found as a degradation product of compound III by Phanerochaete chrysosporium (T. Umezawa, and T. Higuchi, FEBS Lett., 25:123-126, 1985), was also identified from the cultures with compound I, II, and III and degraded to give the arylglycerol (compound VI). An isotopic experiment with ¹³C-labeled compounds II′ and III′ indicated that the carbonate carbon of compound V was derived from the β-phenoxyl groups of β-O-4 substructure.     

Four new β-lactones from the endophytic Streptomyces sp. T1B1

The detailed investigation of endophytic Streptomyces sp. T1B1 was performed during a search for new structural and active compounds. The strain T1B1 was isolated from the old bast tissue of Taxus yunnanensis and determined to be a member of Streptomyces, according to the 16S rRNA analysis. The extracts from the PDA solid fermentation media of Streptomyces sp. T1B1 were purified and four β-lactones were isolated. They were identified as 4α-(3,5-dihydroxy hexyl)-3α-methyl-2-oxetanone (1), 4α-(3-methyl-4-formyloxy-hexyl)-3α-methyl-2-oxetanone (2), 4α-(3,5-dihydroxy-heptyl)-3α-methyl-2-oxetanone (3) and 4α-(3-methyl-4-formyloxy-heptyl)-3α-methyl-2-oxetanone (4) on the basis of spectral data.     

三丫苦的化学成分研究

采用硅胶柱层析从三丫苦的乙酸乙酯萃取物中分离得到6种化合物,经波谱分析鉴定为4,7-二甲氧基呋喃喹啉生物碱(1)、顺式-3,4,5-三羟基-6-乙酰基-7-甲氧基-2,2-二甲基色烷(2)、3-羟基-4-乙氧基-5,7-二甲氧基-6-乙酰-2,2-二甲基色烷(3)、3,5-二羟基-4-乙氧基-6-乙酰基-7-甲氧基-2,2-二甲基色烷(4)、异吴茱萸酮酚(5)和异吴茱萸酮酚甲醚(6)。所有化合物均首次从该植物的根部分离得到。     

Metabolism of non-phenolic diarylpropane lignin substructure model compound by Coriolus versicolor

Abstract A lignin substructure model, 1-(4-ethoxy-3,5-dimethoxyphenyl)-2-(4-ethoxy-3-methoxyphenyl)-propane-1,3-diol(I), was actively metabolized by a white-rot fungus Coriolus versicolor in low nitrogen stationary cultures favouring the ligninolytic activity in the fungus. Cleavage of the dimer I between C_α and C_β of the propanoid side chain was the major degradative reaction by the fungus.     

Acetophenones and terpenoids from Senecio Gallicus

Six new compounds isolated from the aerial part of Senecio gallicus were: 7,11,15-trimethyl-3-methylene hexadecan-1,2-diol diacetate; 7,11,15-trimethyl-3-methylenehexadecan-1,2-diol; 3,5-bis(3-methyl-2-butenyl)-4-acetoxyacetophenone; 3-(2-hydroxy-3-methyl-3-butenyl)-5-(3-methyl-2-butenyl)4-hydroxacetophenone; 3-(2,3-dihydroxy-3-methyl-butyl)-5-(3-methyl-2-butenyl)-4-hydroxyacetophenone and 1,10-epoxy-8α-hydroxy eremophilenolide.     

Quercetin 3-O-beta-glucoside is better absorbed than other quercetin forms and is not present in rat plasma

The effect of the nature of the sugar moiety on quercetin absorption has been investigated in rats. Four groups of rats received an experimental meal containing 20 mg of quercetin equivalents, supplied as quercetin, quercetin 3-O-β-glucoside, quercetin 3-O-β-rhamnoside or rutin. Four hours after the meal, the metabolites identified in hydrolysed plasma were identical in all groups (3'- and 4'-methylquercetin). However, the total concentration of metabolites was markedly different: 11.2±1.8, 2.5±2.0 and 33.2±3.5 μM for the quercetin, rutin, and quercetin 3-glucoside meals respectively. After quercetin 3-rhamnoside consumption, we failed to detect any metabolites in the plasma. These data suggest that the 3-O-glucosylation improves the absorption of quercetin in the small intestine, whereas the binding of a rhamnose to the aglycone markedly depresses it. Additional experiments have shown that the higher plasma levels measured after quercetin 3-glucoside meal compared to the quercetin meal were maintained throughout the 24-hour period following the meal. Using a multi-electrode coulometric detection, together with suitable chromatographic conditions, we were able to distinguish between the conjugated and the glycosylated forms. Thus, we clearly showed the absence of quercetin 3-O-β-glucoside in the plasma from rats fed a diet containing this glucoside. This result suggests that quercetin 3-O-β-glucoside is hydrolysed before or during its intestinal absorption.     

Characterisation of the actions of group I metabotropic glutamate receptor subtype selective ligands on excitatory amino acid release and sodium-dependent re-uptake in rat cerebrocortical minislices

In this study we have tested the effects of a wide range of metabotropic glutamate receptor ligands on (i) depolarisation-evoked efflux of pre-accumulated d-[3H]aspartic acid (d-[3H]asp) from rapidly superfused rat cerebrocortical minislices, and (ii) Na+-dependent uptake of d-[3H]asp into cerebrocortical tissue. Transient elevations in extracellular K+ produced concentration-dependent increases in d-[3H]asp efflux. A submaximally effective concentration (50 mm) was used in all subsequent experiments. The broad-spectrum mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD; EC50 17.8 microm], the group I mGlu-selective agonist (S)-3,5-dihydroxyphenylglycine [(S)-3,5-DHPG; EC50 0.5 microm] and the mGlu5 receptor subtype-selective agonist (RS)-2-chloro-5-hydroxyphenylglycine [(RS)-CHPG; EC50 7.3 microm] all concentration-dependently potentiated high K+-evoked d-[3H]asp efflux in the absence of effects on basal outflow of radiolabel. At concentrations selective for mGlu1 receptors, the antagonists (RS)-1-aminoindan-1,5-dicarboxylic acid [(RS)-AIDA; 10-300 microm]; (+)-2-methyl-4-carboxyphenylglycine [LY367385; 1-100 microm] and 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylate ethyl ester [CPCCOEt, 1-30 microm] all failed to inhibit responses to (S)-3,5-DHPG. However, the broad-spectrum mGlu receptor antagonist (S)-alpha-methyl-4-carboxyphenylglycine [(S)-MCPG; IC50 88.5 microm] together with the recently described mGlu5-selective antagonists, 2-methyl-6-(phenylethynyl)-pyridine (MPEP; IC50 0.6 microm), 6-methyl-2-(phenyl-azo)-3-pyridinol (SIB-1757; IC50 4.4 microm) and (E)-2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893; IC50 3.1 microm), at mGlu5-selective concentrations, all powerfully and concentration-dependently inhibited (S)-3,5-DHPG-evoked responses. Two selective excitatory amino acid (EAA) uptake inhibitors, l-trans-2,4-pyrrolidine dicarboxylate (l-trans-2,4-PDC; IC50 229 microm) and dl-threo-beta-benzyloxyaspartate (dl-TBOA; IC50 665 microm) both inhibited the Na+-dependent uptake of d-[3H]asp into cerebrocortical minislices. Importantly, none of the mGlu ligands utilized in the present study significantly inhibited d-[3H]asp uptake at concentrations shown to potentiate K+-evoked efflux. These data demonstrate for the first time that mGlu5 ligands modulate extracellular EAA concentrations by a direct effect on mGlu5-type autoreceptors on EAA nerve terminals as they evoke clear changes in EAA release in the absence of any effects on EAA uptake. Selective mGlu5 receptor antagonists that show high potency and good central bioavailability may provide novel classes of neuroprotective agents for the treatment of brain disorders associated with abnormal EAAergic neurotransmission.     

Anthraquinones from Vismia species

1,8-Dihydroxy-3-methyl-6-methoxyanthraquinone (physcion) and two derivatives, 7-(trans-3-methyl-1-butenyl)-physcion (vismiaquinone) and 7-(3-methyl-2-oxobutyl)-physcion (vismiaquinone B), were isolated respectively from Vismia cayennensis and V. japurensis.     

New Cholinesterase Inhibitory Constituents from Lonicera quinquelocularis

A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant) led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1–5) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC₅₀ (50% inhibitory effect) values of compounds 3 and 5 against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds 2 and 4 showed weak inhibition profile.     

Benzophenones of Garcinia pseudoguttifera (Clusiaceae)

Four biogenetically related benzophenones have been isolated from the Fijian Garcinia pseudoguttifera. They are: 6-hydroxy-2,4-dimethoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (myrtiaphenone-A); 2,2-dimethyl-8-benzoyl-7-hydroxy-5-methoxy-6-(3-methyl-2-butenyl)benzopy ran (myrtiaphenone-B); 2,6-dihydroxy-4-methoxy-3,5-bis(3-methyl-2-butenyl)benzophenone (vismiaphenone-C) and a new benzophenone, 2,2-dimethyl-8-benzoyl-3,7-dihydroxy-5-methoxy- 6-(3-methyl-2-butenyl)-3,4-dihydrobenzopyran (pseudoguttiaphenone-A). Pseudoguttiaphenone-A could be biogenetically derived from vismiaphenone-C. The major component of G. pseudoguttifera was identified as eupha-8,24-dien-3 beta-ol.     

5-Substituted Pyrimidine L-2′-Deoxyribonucleosides: Synthetic,Quantum Chemical,and NMR Studies

As a part of an ongoing medicinal chemistry, we report here the synthesis and structure evaluation of 1-(2-deoxy-3,5-di-O-acetylpentofuranosyl)-5-[(3-methyl-5-oxo-1-phenyl-4,5-dihydro-4H-pyrazol-4-ylidene) pyrimidine-2,4(1H,3H)-dione 5 and 5-[bis(3-methyl-5-oxo-1-phenyl-4,5-dihydro-4H-pyrazol-4-yl)methyl-1-(2-deoxy-3,5-di-O-acetylpentofuranosyl)pyrimidine-2,4(1H,3H)-dione 6 derived from 3 ′,5 ′-di-O-acetyl-5-formyl-2 ′-deoxy-β-L-uridine 1. Base hydrolysis of compounds 1 and 6 furnished their deacetylated analogues in good yields, whereas hydrolysis of 5 was troublesome. Structural features of these molecules are discussed by NMR spectra analyses and density functional theory quantum chemical calculations. The newly synthesized L-analogues show no significant activity against vaccinia and cowpox viruses.     

Synthesis of methyl ether analogues of sildenafil (Viagra) possessing tyrosinase inhibitory potential

The microwave-assisted synthesis and characterization of the ten new sildenafil (Viagra; 1) analogues 6-15 are described. A detailed structure-activity-relationship (SAR) study revealed that compounds 10 (= 4-ethoxy-N-hydroxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide) and 12 (= S-(2-hydroxyethyl) 4-ethoxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonothioate) are extremely potent mushroom tyrosinase inhibitors, with IC50 values (3.59 and 2.15 microM, resp.) below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and 16.67 microM, resp.). Compounds 10 and 12 are, thus, the currently most-effective inhibitors of tyrosinase, and bear great potential to be used for the treatment of various skin disorders such as hyperpigmentation, which is associated with high production of melanocytes.     

5,2′-dihydroxy-6,7-methylenedioxyisoflavone from seed balls of sugar beet

5,2′-Dihydroxy-6,7-methylenedioxyisoflavone was identified from the seed balls of sugar beet. A neolignan, 6-oxo-2-(4-hydroxy-3,5-dimethoxyphenyl)-3,7-dioxabicyclo-[3.3.0]-octane, and indole-3-carboxylic acid were also isolated.     

Neolignans from an Aniba species

A benzene extract of the trunk of an Aniba species (Lauraceae) contained benzyl benzoate, benzyl salicylate, sitosterol and the neolignans (2S,3S,3aR)-3a-allyl-5-methoxy-3-methyl-2-piperonyl-2,3,3a,6-tetrahydro-6-oxobenzofuran (burchellin); (2S,3S,3aR)-3a-allyl-5-methoxy-3-methyl-2-veratryl-2,3,3a,6-tetrahydro-6-oxobenzofuran; (2S,3S,3aR)-3a-allyl-5,7-dimethoxy-3-methyl-2-veratryl-2,3,3a,6-tetrahydro-6-oxobenzofuran; (2S,3S,5S)-5-allyl-5-methoxy-3-methyl-2-veratryl-2,3,5,6-tetrahydro-6-oxo-benzofuran; (2R,3R)-7-methoxy-3-methyl-5-propenyl-2-veratryl-2,3-dihydrobenzofuran; rel-(1R,5R,6R,7R,8S)-1-allyl-8-hydroxy-3-methoxy-7-methyl-4-oxo-6-piperonylbicyclo[3,2,1]oct-2-ene (guianin); rel-(1S,5S,6S,7R,8R)-1-allyl-8-hydroxy-3,5-dimethoxy-7-methyl-4-oxo-6-piperonylbicyclo[3,2,1]oct-2-ene; rel-(1S,5S,6S,7R,8R)-8-acetoxy-1-allyl-3-hydroxy-5-methoxy-7-methyl-4-oxo-6-piperonyl-bicyclo[3,2,1]oct-2-ene; rel-1S,5S,6S,7R,8R)-8-acetoxy-3,5-dimethoxy-7-methyl-4-oxo-6-piperonylbicyclo[3,2,1]oct-2-ene; rel-(1R,5S,6R,7R)-1-allyl-3-methoxy-7-methyl-4,8-dioxo-6-piperonylbicyclo[3,2,1]oct-2-ene.