Biotransformation of a C-glycosylflavone, abrusin 2''-O-beta-D-apioside, by human intestinal bacteria

After anaerobic incubation of abrusin 2'-O-beta-D-apioside (1) with a human fecal suspension, five metabolites were isolated and identified as abrusin (2), 1-(2',6'-dihydroxy-3',4'-dimethoxyphenyl)-3-(4'-hydroxyphenyl)propan-1- one (5), 5,6-dimethoxybenzene-1,3-diol (6), 3-(4'-hydroxyphenyl)propionic acid (7) and 3-phenylpropionic acid (8). However, methyl ether derivatives of abrusin (4'-O-methylabrusin and 4'-O-, 5-O-dimethylabrusin) resisted degradation under the same conditions.     

PREPARATIVE ISOLATION AND PURIFICATION OF CHEMICAL CONSTITUENTS OF BELAMCANDA BY MPLC, HSCCC AND PREP-HPLC

Combined with medium-pressure liquid chromatography (MPLC) and preparative high-pressure liquid chromatography (Prep-HPLC), high-speed countercurrent chromatography (HSCCC) was successfully applied for separation and purification of isoflavonoids from the extract of belamcanda. HSCCC separation was performed on a two-phase solvent system composed of methyl tert-butyl ether -ethyl acetate - n-butyl alcohol - acetonitrile -0.1% aqueous trifluoroacetic acid at a volume radio of 1:2:1:1:5. Semi-purified peak fractions from HSCCC separation were further purified by Prep-HPLC. Nine well-separated fractions were analyzed by HPLC-UV absorption spectrometry to determine their purities and characterized with ESI-MS(n). Except for peaksland VII (unknown) seven compounds were identified as apocynin (peak II), mangiferin (peak III), 7-O-methylmangiferin (peak IV), hispidulin (peak V), 3'-hydroxyltectoridin (peak VI), iristectorin B (peak VII), isoiridin (peak IX).     

Phenolic constituents from the rhizomes of Gastrodia elata

Gastrodia elata Bl. (Orchidaceae) is an important traditional medicinal plant as well as a famous foodstuff in China. In the present article, the HPLC chromatograms of different preparation processes were reported, and structures of nine phenolic compounds, isolated from Gastrodia elata, were assigned. The isolated compounds were identified as 1,3-bis(4-hydroxybenzyl)citrate (1), gastrodin (2), 4-hydroxybenzyl alcohol (3), 1-(4-beta-D-glucopyranosyloxybenzyl)citrate (4), 4-hydroxybenzaldehyde (5), parishin B (6), 4-hydroxybenzyl methyl ether (7), 4-hydroxybenzyl ethyl ether (8), and 4-(4'-hydroxybenzyl)phenol (9). Compounds 1 and 4, named as parishin D and E, were new. Their structures were elucidated on the basis of spectral analyses, including 2D NMR spectroscopy.     

Photochemical reaction mechanisms of 2-nitrobenzyl compounds: methyl ethers and caged ATP

The mechanism of methanol photorelease from 2-nitrobenzyl methyl ether (1) and 1-(2-nitrophenyl)ethyl methyl ether (2), and of ATP release from adenosine-5'-triphosphate-[P(3)-(1-(2-nitrophenyl)ethyl)] ester ('caged ATP', 3) was studied in various solvents by laser flash photolysis with UV-vis and IR detection. In addition to the well-known primary aci-nitro transients (A, lambda(max) approximately 400 nm), two further intermediates preceding the release of methanol, namely the corresponding 1,3-dihydrobenz[c]isoxazol-1-ol derivatives (B) and 2-nitrosobenzyl hemiacetals (C), were identified. The dependencies of the reaction rates of A-C on pH and buffer concentrations in aqueous solution were studied in detail. Substantial revision of previously proposed reaction mechanisms for substrate release from 2-nitrobenzyl protecting groups is required: (a) A novel reaction pathway of the aci-tautomers A prevailing in buffered aqueous solutions, e.g., phosphate buffer with pH 7, was found. (b) The cyclic intermediates B were identified for the first time as the products formed by the decay of the aci-tautomers A in solution. A recently proposed reaction pathway bypassing intermediates B (Corrie et al. J. Am. Chem. Soc., 2003, 125, 8546-8554) is shown not to be operative. (c) Hemiacetals C limit the release rate of both 1 (pH < 8) and 2 (pH < 10). This observation is in contrast to a recent claim for related 2-nitrobenzyl methyl ethers (Corrie et al.). Our findings are important for potential applications of the 2-nitrobenzyl protecting group in the determination of physiological response times to bioagents ('caged compounds').     

8-羟基喹啉席夫碱衍生物及其金属配合物的合成及荧光性质研究

设计合成了三种新的8-羟基喹啉席夫碱衍生物4-(8-羟基喹啉-5-亚胺甲基)-7-甲氧基苯并吡喃-2-酮(3a),4-(8-羟基喹啉-5-亚胺甲基)-7-己氧基苯并吡喃-2-酮(3b)和4-(8-羟基喹啉-5-亚胺甲基)-7-十八烷氧基苯并吡喃-2-酮(3c)及其铝、锌配合物,产物结构经1H(13C)NMR,MS,HRMS,IR和元素分析表征,研究了它们的荧光发光性能.     

Synthesis of 1-[(3-Halo-1-Hydroxy-2-Propoxy)methyl]uracil and Thymine as Potential Antiviral Agents

3′-Halogen acyclonucleoside analogs have been prepared. The starting material, benzyl glycidyl ether (5) , prepared from eplchlorohydrin and sodium benzyloxidc, underwent ring opening by soft halogen ions to give l-benzyloxy-3-fluoro-2-propanol (6) , l-bcnzyloxy-3-chloro-2-propanol (7) , and l-benzyloxy-3- bromo-2-propanol (8) respectively. The treatment of 5 with lithium iodide in the presence of acetic acid provided 1-benzyloxy-3-iodo-2-propanol (9) . The treatment of 8 with sodium iodide in anhydrous acetone also produced l-benzyloxy-3-iodo-2-propanol (9) . Chloromethylation of these halohydrins 6-9 using paraformaldehyde and hydrogen chloride gas produced the chloromcthyl ethers 10-13 . These chloromethyl ethers without further purification were allowed to react with the silylated bases 16-17 , previously prepared by silylating the bases 14-15 with HMDS in the presence of ammonium sulfate to give 1- [(l-benzyloxy-3-halogen-2-propoxy)methyl]uracils and thymines 19-25 . The target compounds 26-33 were obtained respectively after the debcnzylation of 18-25 . Compounds 26, 27, 30 and 31 had no significant cell toxicity in the range of concentrations 0.001-20 mM. Compounds 26, 27, 28 and 29 have no significant activity against HSV II (for less than 2 mM there is a cytopathic effect). Compounds 30, 31, 32 and 33 show no activity against HSV II virus even at the level 20 mM.     

α-Methylidene- and α-Alkylidene-β-lactams from Nonproteinogenic Amino Acids

Treatment of methyl 2-(1-hydroxyalkyl)prop-2-enoates 1 with conc. HBr solution afforded methyl (Z)-2-(bromomethyl)alk-2-enoates 2 , which were transformed regioselectively into N-substituted methyl (E)-2- (aminomethyl)alk-2-enoates 3 (S_N2 reaction) and into N-substituted methyl 2-(1-aminoalkyl)prop-2-enoates 4 (S_N2′ reaction). Regiocontrol of nucleophilic attack by amine was accomplished simply by choice of solvent, the S_N2 reaction occurring in MeCN and the S_N2′ reaction in petroleum ether. Hydrolysis and lactamization afforded β-lactams 7 and 8 , containing an exocyciic alkylidene and methylidene group at C(3), respectively.     

Labdane diterpenes from the rhizomes of Hedychium coronarium

A new labdane diterpenoid, (E)-labda-8(17),12-dien-15,16-olide (1) together with eight known compounds, coronarin D (2), coronarin D methyl ether (3), coronarin D ethyl ether (4), isocoronarin D (5), coronarin B (6), labda-8(17),11,13-trien-15,16-olide (7), (E)-labda-8(17),12-diene-15,16-dial (8) and 16-hydroxylabda-8(17),11,13-trien-15,16-olide (9), are isolated from the rhizomes of Hedychium coronarium. Compounds 2-4, 5 and 9 are isolated as mixtures of C-15, C-14 and C-16 epimers, respectively. Their structures are determined on the basis of their spectroscopic data. The epimeric mixtures of 2 and 3 have not been reported before. Some of them were evaluated for their cytotoxicity.     

Reactions of hydro(pero)xy derivatives of polyunsaturated fatty acids/esters with nitrite ions under acidic conditions. Unusual nitrosative breakdown of methyl 13-hydro(pero)xyoctadeca-9,11-dienoate to a novel 4-nitro-2-oximinoalk-3-enal product

13(S)-hydroperoxy- and 13(S)-hydroxyoctadeca-9,11-dienoic acids (1a/b), 15(S)-hydroperoxy- and 15(S)-hydroxyeicosa-5,8,11,13-tetraenoic acids (2a/b), and their methyl esters reacted smoothly with NO2- in phosphate buffer at pH 3-5.5 and at 37 degrees C to afford mixtures of products. 1b methyl ester gave mainly the 9-nitro derivative 3b methyl ester (11% yield) and a peculiar breakdown product identified as the novel 4-nitro-2-oximinoalk-3-enal derivative 4 methyl ester (15% yield). By GC-MS hexanal was also detected among the products. Structures 3b and 4 methyl esters were secured by 15N NMR analysis of the products prepared from 1b methyl ester upon reaction with Na15NO2. 4 methyl ester (14% yield) was also obtained from 1a methyl ester along with the nitrated hydroperoxy derivative 3a methyl ester (10% yield). Under the same conditions, 2a/b methyl esters gave mainly the corresponding nitrated derivatives 5a/b, with no detectable breakdown products, whereas the model compound (E,E)-2,4-hexadienol (6) afforded two main nitrated derivatives identified as 7 and 8. A reaction pathway for 1a/b methyl esters was proposed involving conversion of nitronitrosooxyhydro(pero)xy intermediates which would partition between two competing routes, viz., loss of HNO2, to give 3a/b methyl esters, and a remarkably facile fission leading to 4 methyl ester and hexanal.     

Selective ther cleavage in the aporphine series. Conversion of (S)-bulbocapnine into (S)-corytuberine and (S)-corydine methyl ether.

Bulbocapnine methyl ether ( 2 ), on treatment with boron halides, affords the aporphine-1,2-diol ( 3 ), the novel aporphines 5 and 6 or the phenanthrene derivative 11 depending on the reaction conditions. 3 can be further transformed into corydine methyl ether ( 4 ); 6 has been converted to corytuberine ( 8 ). Similarly, dehydrobulbocapnine methyl ether 9 was converted to 10 .     

Studies on Balanites aegyptiaca fruits, an antidiabetic Egyptian folk medicine

An aqueous extract of mesocarps of the fruits of Balanites aegyptiaca exhibited a prominent antidiabetic activity by oral administration in streptozotocin induced diabetic mice. From one of the active fractions of this extract, two new steroidal saponins were isolated, and their structures were determined as 26-O-beta-D-glucopyranosyl-(25R)-furost-5-ene-3 beta,22,26-triol 3-O-[alpha-L-rhamnopyranosyl-(1----2)]-[beta-D-xylopyranosyl-(1---- 3)]-[alpha-L-rhamnopyranosyl-(1----4)]-beta-D-glucopyranoside and its 22-methyl ether. In addition, two known saponins, 26-O-beta-D-glucopyranosyl-(25R)-furost-5-ene-3 beta,22,26-triol 3-O-(2,4-di-O-alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside and its methyl ether were isolated and identified. It was revealed that the individual saponins did not show antidiabetic activity, while the recombination of these saponins resulted in significant activity. From an ethanolic extract of the epicarps, two known flavonol glycosides, isorhamnetin-3-O-robinobioside and isorhamnetin-3-O-rutinoside were isolated and identified.     

Stereoselective synthesis of 1-methoxyspiroindoline phytoalexins and their amino analogues

The stereoselective synthesis of the spiroindoline phytoalexin (R)-(+)-1-methoxyspirobrassinin and its unnatural (S)-(−)-enantiomer were achieved by the bromine-induced spirocyclization of 1-methoxybrassinin using chiral auxiliaries (+)- and (−)-menthol, followed by oxidation of the obtained menthyl ethers. The TFA-catalyzed methanolysis of chiral 1-methoxyspirobrassinol menthyl ethers provided (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether and its other three unnatural stereoisomers. The enantiomers of the 2-amino analogues of the indole phytoalexin (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether were prepared by the TFA-catalyzed replacement of the chiral alkoxy group with an amine. The synthesized compounds were tested in vitro on cancer cell lines and examined with enantiopure 2-amino analogues of the indole phytoalexin (2R,3R)-(−)-1-methoxyspirobrassinol methyl ether, which showed in most cases, lower activity than the corresponding racemates.     

Thermodynamic properties (enthalpy, bond energy, entropy, and heat capacity) and internal rotor potentials of vinyl alcohol, methyl vinyl ether, and their corresponding radicals

Vinyl alcohols (enols) have been discovered as important intermediates and products in the oxidation and combustion of hydrocarbons, while methyl vinyl ethers are also thought to occur as important combustion intermediates. Vinyl alcohol has been detected in interstellar media, while poly(vinyl alcohol) and poly(methyl vinyl ether) are common polymers. The thermochemical property data on these vinyl alcohols and methyl vinyl ethers is important for understanding their stability, reaction paths, and kinetics in atmospheric and thermal hydrocarbon-oxygen systems. Enthalpies , entropies , and heat capacities (C(p)()(T)) are determined for CH(2)=CHOH, C(*)H=CHOH, CH(2)=C(*)OH, CH(2)=CHOCH(3), C(*)H=CHOCH(3), CH(2)=C(*)OCH(3), and CH(2)=CHOC(*)H(2). Molecular structures, vibrational frequencies, , and C(p)(T) are calculated at the B3LYP/6-31G(d,p) density functional calculation level. Enthalpies are also determined using the composite CBS-Q, CBS-APNO, and G3 methods using isodesmic work reactions to minimize calculation errors. Potential barriers for internal rotors are calculated at the B3LYP/6-31G(d,p) level and used to determine the hindered internal rotational contributions to entropy and heat capacity. The recommended ideal gas phase values calculated in this study are the following (in kcal mol(-1)): -30.0, -28.9 (syn, anti) for CH(2)=CHOH; -25.6, -23.9 for CH(2)=CHOCH(3); 31.3, 33.5 for C(*)H=CHOH; 27.1 for anti-CH(2)=C(*)OH; 35.6, 39.3 for C(*)H=CHOCH(3); 33.5, 32.2 for CH(2)=C(*)OCH(3); 21.3, 22.0 for CH(2)=CHOC(*)H(2). Bond dissociation energies (BDEs) and group additivity contributions are also determined. The BDEs reveal that the O-H, O-CH(3), C-OH, and C-OCH(3) bonds in vinyl alcohol and methyl vinyl ether are similar in energy to those in the aromatic molecules phenol and methyl phenyl ether, being on average around 3 kcal mol(-1) weaker in the vinyl systems. The keto-enol tautomerization enthalpy for the interconversion of vinyl alcohol to acetaldehyde is determined to be -9.7 kcal mol(-1), while the activation energy for this reaction is calculated as 55.9 kcal mol(-1); this is the simplest keto-enol tautomerization and is thought to be important in the reactions of vinyl alcohol. Formation of the formyl methyl radical (vinoxy radical/vinyloxy radical) from both vinyl alcohol and methyl vinyl ether is also shown to be important, and its reactions are discussed briefly.     

Antioxidant galloylated flavonol glycosides from Calliandra haematocephala

Three new acylated quercetin rhamnosides have been isolated from the leaves and stem of Calliandra haematocephala Hassk. (Fabaceae) and their structures were established as quercitrin 2'-O-caffeate (1), quercitrin 3'-O-gallate (2) and quercitrin 2',3'-di-O-gallate (3). Also, 17 known compounds were identified as gallic acid (4), methyl gallate (5), caffeic acid (6), myricitrin (7), quercitrin (8), myricetin 3-O-beta-D-4C1-glucopyranoside (9), afzelin (10), isoquercitrin (11), myricetin 3-O-(6'-O-galloyl)-beta-D-glucopyranoside (12), myricitrin 2'-O-gallate (13), quercitrin 2'-O-gallate (14), afzelin 2'-O-gallate (15), myricitrin 3'-O-gallate (16), afzelin 3'-O-gallate (17), 1,2,3,4,6-penta-O-galloyl-beta-D-4C1-glucopyranose (18), myricitrin 2',3'-di-O-gallate (19), quercetin 3-O-methyl ether (20), for the first time from the genus Calliandra except for 6. Compounds 7, 8, 13, 14, 16 and 19 exhibited moderate to strong radical scavenging properties on lipid peroxidation, hydroxyl radical, superoxide anion generation and DPPH radical in comparison with that of quercetin as a positive control in vitro. Compounds 7 and 8 exhibited lethal effect towards brine shrimp Artemia salina.     

9-Hydroxy-2-methyl-4H-pyrido[1,2-α] pyrimidin-4-one and its derivatives

2-Amino-3-(o-bromobenzyloxy)pyridine ( 1 ) and ethyl acetoacetate gave 9-(o-bromobenzyl-oxy)-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 2 ) in 2% yield. When 1 and methyl β-amino-crotonate ( 3 ) were reacted, benzyl ether cleavage occurred and the products were 9-hydroxy-2-methyl-4H-pyrido[1,2-α]pyrimidin-4-one ( 4 ) and its ammonium salt ( 5 ). These observations led to an alternative synthesis in which 2-amino-3-pyridinol ( 6 ) and either 3 or methyl acetoacetate, ( 8 ) in diethylbenzene at 185° gave 4 in 86 and 87% yields, respectively, and the anion of 4 and o-bromobenzyl bromide gave 2 in 61% yield. Even in diethylbenzene at 185°, 1 and 8 gave only trace amounts of 2 . Thus, o-bromobenzylation of the 3-hydroxyl group in 6 markedly decreased the reactivity of the amino group in 6 toward reactions with acetoacetic esters.     

New biphasic solvent system based on cyclopentyl methyl ether for the purification of a non‐polar synthetic peptide by pH‐zone refining centrifugal partition chromatography

A new type 1 ternary biphasic system composed of cyclopentyl methyl ether, dimethylformamide and water was developed, characterized and successfully used for the purification of a lipophilic, protected peptide by pH‐zone refining centrifugal partition chromatography. The protected peptide is an 8‐mer, key intermediate in bivalirudin (Angiomax®) synthesis and shows a very low solubility in the solvents usually used in liquid chromatography. All ionic groups, except the N‐terminal end of the peptide, are protected by a benzyl group. The purification of this peptide was achieved with a purity of about 99.04% and a recovery of 94% using the new ternary biphasic system cyclopentyl methyl ether/dimethylformamide/water (49:40:11, v/v) in the descending pH‐zone refining mode with triethylamine (28 mM) as the retainer and methanesulfonic acid (18 mM) as the eluter.     

Über die absolute Konfiguration der Visnagane

(+)-cis-Khellactone methyl ether ( 4 ) and (?)-trans-khellactone methyl ether ( 6 ) had earlier been assigned the absolute configurations 3′-S; 4′-S and 3′-S; 4′-R, respectively, on the basis of the FREUDENBERG , rule. Both compounds together with their defunctionalised derivatives (?)- 7 and (+)- 8 (=(+)-lomatin), obtained from a mixture of (+)-visnadin ( 1 ) and (+)-samidin ( 2 ), were investigated by the HOREAU method. A conformational analytical study showed that the optical yield should rise in the order 4 < 6 < 7 , 8. This order was found and the α-phenylbutyric acid liberated was always dextrorotatory. The centre 3′ of the khellactones and their derivatives must be R-chiral and not S. Treatment of (?)- 6 with pyridinium perbromide gave (?)-trans-3-bromokhellactone methyl ether ( 11 ) as orthorhombic crystals. The X-ray crystal structure determination was made using the anomalous scattering of the Mo-K α radiation by Br. The result, — centre 3′ R-chiral (fig. g) — showed that the HOREAU method was correct.     

Perfluoroalkylated eight- and nine-membered benzoheterocycles from F-2-methyl-2-pentene

The reactions of $\text{F}$-2-methyl-2-pentene (1) with several $\text{ortho}$- difunctional benzenes afforded eight- and nine-membered benzoheterocyclic compounds carrying perfluoroalkyl groups. Salicylic acid, salicylaldehyde, and their methyl or chloro derivatives reacted in triethylamine-acetonitrile system giving perfluoroalkylated 2H,6H-1,5-benzodioxocin-2,6-dione (8) and 4H,6H-1,5-benzodioxocin (9) compounds respectively, while phthalyl alcohol and o-hydroxyphenethyl alcohol in triethylamine-diethyl ether system gave perfluoroalkylated 1H,3H,7H-2,6- and 4H,6H,7H-1,5-benzodioxonin compounds, (10) and (11). o-Aminobenzyl alcohol and (1) in diethyl ether afforded a perfluoroalkylated benzoxazocinobenzoxazocinone compound (15).     

Synthèse de l'évernine

Synthesis of Evernin Two syntheses of the depside evernin 6 are described. Condensation of methyl acetoacetate and methyl crotonate followed by aromatization and reduction with Raney-Ni led to methyl orsellinate (3) . The condensation of everninic acid (4) , obtained by partial methylation of 3 and saponification of the methyl ester, with methyl 2, 4-dihydroxy-3, 6-dimethylbenzoate (methyl β-orcin carboxylate) (5) in presence of cyclohexylcarbodiimide gave evernin ( 6 ). In a second syntheis methyl dihydroorsellinate (1) was regiospecifically converted into its 4-methyl enol ether and aromatized via the benzene selenenyl derivative to yield methyl evernate (7) . Benzylation followed by saponification gave the free acid 8 . Methyl β-orcin carboxylate (5) was synthesized in an analogous way from methyl 3,6-dimethyl-2,4-dioxocyclohexanecarboxylate. Condensation of 8 with the methyl ester 5 by treatment with trifluoroacetic anhydride in toluene yielded 9 , which could be converted into evernin ( 6 ) by hydrogenolysis of the benzyl ether.     

Electrochemical polymerization of functionalized thiophene derivatives for the immobilization of proteins

The hydroxy group of 3-(2-hydroxyethyl)thiophene was protected as methyl ether 1 and as dimethyl tert-butyl silyl ether 5 before anodic polymerization. The poly[3-(2-methoxyethyl)thiophene] 2 was prepared by electrochemical homopolymerization of 1 . Ether cleavage was carried out in the polymer film 2 and the resulting poly [3-(2-hydroxyethyl)thiophene] ( 3 ) was activated with cyanogen bromide to immobilize alcohol dehydrogenase. Silylether 5 did not undergo homopolymerization but copolymerization of 5 with 3-methylthiophene ( 4 ) was successful. After cleavage of the protecting group the resulting copolymer 7 was activated by cyanuric chloride, and chymotrypsin was immobilized. Electrocopolymerization of thiophene-3-acetic acid ( 8 ) and 3-methylthiophene ( 4 ) under various conditions produces copolymer 9 . By activation of the carboxylic groups with N,N'-dicyclohexylcarbodiimide (DCC) lactate oxidase (LOD) was bond to the surface of the electrode to form a lactate sensor.