Xanthones from Lawsonia inermis

Two new xanthones isolated from Lawsonia inermis have been characterised as 1, 3-dihydroxy-6, 7-dimethoxyxanthone and 1-hydroxy-3, 6-diacetoxy-7-methoxyxanthone and named laxanthone-I and II, respectively.     

红厚壳枝条的化学成分

从红厚壳(Calophyllum inophyllum Linn.)枝条乙醇提取物中分离得到11个化合物,通过光谱分析,鉴定其结构为:6-羟基-2,3-二甲氧基 酮 ( 1 ) ,1,3,7-三羟基 酮 ( 2 ) ,1,3,7-三羟基-8-甲氧基 酮( 3 ) ,7-羟基-1,3-二甲氧基 酮( 4 ) ,伪蒲公英甾醇( 5 ) ,1,3,6-三羟基-5,7-二甲氧基 酮( 6 ) ,2-羟基-1-甲氧基 酮 ( 7 ) ,2-羟基-1,8-二甲氧基 酮 ( 8 ) ,1,3,5-三羟基-2-甲氧基 酮 ( 9 ) ,4-羟基 酮 ( 10 ) ,1,3,5-三羟基 酮 ( 11 ) 。化合物 2 ~ 5 为首次从红厚壳属植物中得到,化合物 6 ~ 8 为首次从该植物中得到,化合物 1 为一新的天然产物。细胞毒活性测试结果表明,化合物 9 对人胃癌细胞(SGC-7901)的增殖显示出生长抑制活性, 其IC₅₀值为1.8×10^-5 mol/L。     

Volubolin,a 4-phenyl-2H-1-benzopyran-2-one from Dalbergia volubilis

From the ether soluble portion of a methanolic extract of young non-green branches of Dalbergia volubilis, sitosterol, 7-hydroxy-4-methyl-2H-1-benz     

Constitutions of diarylpropanoids from Virola multinervia

The wood of Virola multinervia Ducke (Myristicaceae) contains sitosterol, stigmasterol and two novel diarylpropanoids virolane [1-(2-hydroxy-4-methoxyphenyl)-3-(3,4-methylenedioxyphenyl)-propane] and virolanol [2-hydroxy-1-(2-hydroxy-4-methoxyphenyl)-3-(3,4-methylenedioxyphenyl)-propane].     

Xanthones from Tovomita pyrifolium

The wood of Tovomita pyrifolium (Guttiferae) contains the novel tovopyrifolins A [1,6-dihydroxy-7-methoxy-5-prenyl-6′,6′-dimethylpyrano (2′,3′:3,2)xanthone], B (1,5-dihydroxy-3,4-dimethoxyxanthone) and C (1,3,5-trihydroxy-2-methoxyxanthone) and also the known tovophyllins A and B [structure revised to 1,6-dihydroxy-5-prenyl-6′, 6′-dimethylpyrano(2′,3′:3,2)-6″,6″-dimethylpyrano(2″,3″:7,8)xanthone].     

Glucosinolates in Sesamoides canescens and S. pygmaea: Identification of 2-(α-l-arabinopyranosyloxy)-2-phenylethylglucosinolate

A new natural product, 2-(α-l-arabinopyranosyloxy)-2-phenylethylglucosinolate, has been isolated from Sesamoides canescens. This glucosinolate together with 2-hydroxy-2-phenylethylglucosinolate and 2-phenetliylglucosinolate in a 1:1:1 ratio constitutes about 90 % of the total glucosinolate pool in green parts of the plant. Phenethylglucosinolate constitutes about 70 % of the total glucosinolate pool in green parts of S. pygmaea together with minor amounts of the two other glucosinolates. In addition, both plants contain at least seven other glucosinolates. The structure of the new natural product has been confirmed by transformations into d-glucose, l-arabinose, N-(2-(α-l-arabinopyranosyloxy)-2-phenylethyl)thiourea, 3-(α-l-arabinopyranosyloxy)-3-phenylpropionitrile and 3-hydroxy-3-phenylpropionic acid, respectively. The significance of this investigation is briefly discussed in relation to the methods used in glucosinolate analysis, chemotaxonomy and possible catabolic transformation of glucosinolates into amines.     

Flavans from Zephyranthes flava

A new optically active flavan aglucone, 7-hydroxy-3′,4′-methylenedioxyflavan, and its 7-glucoside have been isolated from the bulbs of Zephyranthes flava, collected at flowering. Additionally, two known flavans, 7,4′-dihydroxy-3′-methoxyflavan and 7-methoxy-2′-hydroxy-4′,5′-methylenedioxyflavan, have been isolated for the first time from this species. The structures of these flavans have been established by comprehensive analyses (UV, IR, ¹H NMR, ¹³C NMR, mass spectrometry, [α]_D) of the compounds and their acetates, and also by chemical correlation.     

Arylbenzofurans from Dalbergia parviflora

The isolation of two polysubstituted arylbenzofurans from the heartwood of Dalbergia parviflora is described. Their structures were elucidated mainly by spectroscopic techniques (UV, IR, ¹H and ¹³C NMR). They were named parvifuran (5-hydroxy-6-methoxy-3-methyl-2-phenylbenzofuran) and isoparvifuran (5-hydroxy-6-methoxy-2-methyl-3-phenylbenzofuran) and are the first compounds of this class isolated from a Dalbergia species.     

New tetraoxygenated xanthones of Canscora decussata

From the alcoholic extract of Canscora decussata Schult (Gentianaceae), the previously unreported 1,3,6,7-tetrahydroxyxanthone (I), 1,3,5,6-tetrahydroxyxanthone-C₂-glucoside (II), and 1,5,6-trihydroxy-3-methoxyxanthone (III), have been isolated and identified. The structures of these xanthones have been established by chemical transformations, synthesis (in case of III), and spectral (UV, IR, PMR, MS) evidence. II and III have not been encountered before in nature, while I is reported for the first time in this genus. The significance of mass spectral fragmentation in the structural elucidation of oxygenated xanthones is discussed.     

Xanthones of Centaurium pulchellum

1-Hydroxy-3,7,8-trimethoxyxanthone, 1,8-dihydroxy-3,7-dimethoxyxanthone and 1,8-dihydroxy-3,5-dimethoxyxanthone have been isolated from the whole plant of Centaurium pulchellum; the compounds were characterized by UV and NMR spectroscopy.     

Guianin: A neolignan from Aniba guianensis

The wood of Aniba guianensis Aubl. (Lauraceae) contains benzyl benzoate, benzyl salicylate, sitosterol, O-methyleugenol, O-methylisoeugenol and the neolignan guianin for which the structure of 1-allyl-8-hydroxy-3-methoxy-7-methyl-4-oxo-6-piperonylbicyclo[3,2,1]oct-2-ene (VI) is proposed.     

Genetic deletion of apolipoprotein A-I increases airway hyperresponsiveness,inflammation, and collagen deposition in the lung

The relationship between high-density lipoprotein and pulmonary function is unclear. To determine mechanistic relationships we investigated the effects of genetic deletion of apolipoprotein A-I (apoA-I) on plasma lipids, paraoxonase (PON1), pro-inflammatory HDL (p-HDL), vasodilatation, airway hyperresponsiveness and pulmonary oxidative stress, and inflammation. ApoA-I null (apoA-I^−/−) mice had reduced total and HDL cholesterol but increased pro-inflammatory HDL compared with C57BL/6J mice. Although PON1 protein was increased in apoA-I^−/− mice, PON1 activity was decreased. ApoA-I deficiency did not alter vasodilatation of facialis arteries, but it did alter relaxation responses of pulmonary arteries. Central airway resistance was unaltered. However, airway resistance mediated by tissue dampening and elastance were increased in apoA-I^−/− mice, a finding also confirmed by positive end-expiratory pressure (PEEP) studies. Inflammatory cells, collagen deposition, 3-nitrotyrosine, and 4-hydroxy-2-nonenal were increased in apoA-I^−/− lungs but not oxidized phospholipids. Colocalization of 4-hydroxy-2-nonenal with transforming growth factor β-1 (TGFβ-1 was increased in apoA-I^−/− lungs. Xanthine oxidase, myeloperoxidase and endothelial nitric oxide synthase were increased in apoA-I^−/− lungs. Dichlorodihydrofluorescein-detectable oxidants were increased in bronchoalveolar lavage fluid (BALF) in apoA-I^−/− mice. In contrast, BALF nitrite+nitrate levels were decreased in apoA-I^−/− mice. These data demonstrate that apoA-I plays important roles in limiting pulmonary inflammation and oxidative stress, which if not prevented, will decrease pulmonary artery vasodilatation and increase airway hyperresponsiveness.     

Non-reversibility of the isoleucine-acetate pathway in Datura

Five-month-old Datura meteloides plants were fed via the roots with 3-hydroxy-2-methylbutanoic acid-[1-¹⁴C] and isoleucine-[U-¹⁴C] as a positive control. After 5 days the plants were collected and in each case the root alkaloids 3α,6β-ditigloyloxytropane, 3α,6β-ditigloyloxytropan-7β-ol, meteloidine, hyoscine and hyoscyamine were isolated. Whereas isoleucine served as a precursor for the tiglic acid moieties 3-hydroxy-2-methylbutanoic acid did not.     

Isolation and crystal structure of 5-hydroxy-2,8-dimethyl-6,7-dimethoxybenzopyran-4-one from Couepia paraensis

A highly substituted chromone constituent of Couepia paraensis was isolated and identified as 5-hydroxy-2,8-dimethyl-6,7-dimethoxychromone by spect     

Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1

Cytochrome P450 (P450 or CYP) 46A1 is expressed in brain and has been characterized by its ability to oxidize cholesterol to 24S-hydroxycholesterol. In addition, the same enzyme is known to further oxidize 24S-hydroxycholesterol to the 24,25- and 24,27-dihydroxy products, as well as to catalyze side-chain oxidations of 7α-hydroxycholesterol and cholestanol. As precursors in the biosynthesis of cholesterol, 7-dehydrocholesterol has not been found to be a substrate of P450 46A1 and desmosterol has not been previously tested. However, 24-hydroxy-7-dehydrocholesterol was recently identified in brain tissues, which prompted us to reexamine this enzyme and its potential substrates. Here we report that P450 46A1 oxidizes 7-dehydrocholesterol to 24-hydroxy-7-dehydrocholesterol and 25-hydroxy-7-dehydrocholesterol, as confirmed by LC-MS and GC-MS. Overall, the catalytic rates of formation increased in the order of 24-hydroxy-7-dehydrocholesterol < 24-hydroxycholesterol < 25-hydroxy-7-dehydrocholesterol from their respective precursors, with a ratio of 1:2.5:5. In the case of desmosterol, epoxidation to 24S,25-epoxycholesterol and 27-hydroxylation was observed, at roughly equal rates. The formation of these oxysterols in the brain may be of relevance in Smith-Lemli-Opitz syndrome, desmosterolosis, and other relevant diseases, as well as in signal transduction by lipids.     

1,2,3-Trioxygenated glucosyloxyxanthones from Polygala triphylla

Four B-ring oxygen-free trioxygenated xanthones, viz. 1-OH-2,3-(OMe)₂-, 1,2,3-(OMe)₃-, 1-OH-2,3- (OCH₂O)-, 1-OMe-2,3-(OCH₂O)-xanthone, two B-ring oxygen-free glucosyloxyxanthones, viz. 1-O-gl.-2-OH-3-OMe- and 1-O-gl.-2,3-(OCH₂0)-xanthone, and a pentaoxygenated xanthone, 1-OMe-2,3,6,7-(OCH₂O)₂-xanthone, have been isolated from the flowering top of Polygala triphylla. The xanthones have been characterized on the basis of chemical transformation, comprehensive spectral evidence, and by direct comparison where possible. This is the first report of occurrence of the glucosyloxyxanthones in nature. The biochemical significance of these chemical characters in higher plants is appraised.     

On the mechanism of accumulation of cholestanol in the brain of mice with a disruption of sterol 27-hydroxylase

The rare disease cerebrotendinous xanthomatosis (CTX) is due to a lack of sterol 27-hydroxylase (CYP27A1) and is characterized by cholestanol-containing xanthomas in brain and tendons. Mice with the same defect do not develop xanthomas. The driving force in the development of the xanthomas is likely to be conversion of a bile acid precursor into cholestanol. The mechanism behind the xanthomas in the brain has not been clarified. We demonstrate here that female cyp27a1^−/− mice have an increase of cholestanol of about 2.5- fold in plasma, 6-fold in tendons, and 12-fold in brain. Treatment of cyp27a1^−/− mice with 0.05% cholic acid normalized the cholestanol levels in tendons and plasma and reduced the content in the brain. The above changes occurred in parallel with changes in plasma levels of 7α-hydroxy-4-cholesten-3-one, a precursor both to bile acids and cholestanol. Injection of a cyp27a1^−/− mouse with ²H₇-labeled 7α-hydroxy-4-cholesten-3-one resulted in a significant incorporation of ²H₇-cholestanol in the brain. The results are consistent with a concentration-dependent flux of 7α-hydroxy-4-cholesten-3-one across the blood-brain barrier in cyp27a1^−/− mice and subsequent formation of cholestanol. It is suggested that the same mechanism is responsible for accumulation of cholestanol in the brain of patients with CTX.     

A new chromanone acid from the bark of Calophyllum dryobalanoides

A new chromanone acid, calodryobalanoic acid, along with six known compounds, apetalic acid, isoblancoic acid, lupeol, 1-hydroxy-2-methoxyxanthone, 1,7-dihydroxy-3-methoxyxanthone, and 5,7,4′-trihydroxyflavanone, was isolated from the bark of Calophyllum dryobalanoides collected in Vietnam. The structure of the new compound was elucidated using mainly 1-D and 2-D NMR techniques (¹H and ¹³C NMR, HSQC, HMBC, COSY, and NOESY) and IR spectroscopy. The stereochemistry was determined on the basis of NMR results and DFT calculations.     

Inhibitors of HIV protease: Unique non-peptide active site templates

New templates were designed and prepared which straddle the active site of HIV-1 protease. These templates were designed to be ‘flexible scaffolds’ upon which substituents could be appended to fill the pockets of HIV protease. The new templates prepared and analysed were 4-hydroxy-5H-furan-2-ones, 4-hydroxy-5,6-dihydropyrones, 3-hydroxy-cyclohex-2-enones, and 4-hydroxy-2(1H)-pyridinones, of which the 4-hydroxy- 5,6-dihydropyrones were found to be the most potent inhibitors of HIV-1 protease.     

A substituted 1,2-diarylethane from Cymbidium giganteum

In addition to sitosterol and taraxerone, a new substituted 1,2-diarylethane, gigantol has been isolated from Cymbidium giganteum and characterized as 1-(3′-hydroxy-5′-methoxyphenyl-2-(4″-hydroxy-5″-methoxyphenyl)ethane on the basis of physicochemical data and through synthesis of its derivative.