Aromatic diglycosides from Cladogynos orientalis

Two unusual aromatic diglycosides with galloyl substitution, 4'-O-galloyl-violutoside and 4'-O-galloyl-benzyl-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside, were isolated from the aerial portion of Cladogynos orientalis along with isovitexin, apigenin 6-C-(2'-O-galloyl)-beta-D-glucopyranoside, apigenin 8-C-(2'-O-galloyl)-beta-D-glucopyranoside, syringic acid beta-D-glucopyranoside, 3,4,5-trimethoxyphenyl beta-D-glucopyranoside, (6S,9R)-roseoside, and violutioside. The structural elucidations were based on analyses of chemical and spectroscopic data by including 1D and 2D NMR analyses.     

(6S)-Hydroxy-3-oxo-alpha-ionol glucosides from Capparis spinosa fruits

Two new (6S)-hydroxy-3-oxo-alpha-ionol glucosides, together with corchoionoside C ((6S,9S)-roseoside) and a prenyl glucoside, were isolated from mature fruits of Capparis spinosa. The structures were established on the basis of spectroscopic, chiroptic and chemical evidence. In addition, the 13C-resonance of C-9 was found to be of particular diagnostic value in assigning the absolute configuration at that center in ionol glycosides. The alpha-ionol derivatives are metabolites of (+)-(S)-abscisic acid.     

羊角拗茎的化学成分及其抗炎活性研究

探讨羊角拗茎的化学成分及其抗炎活性,采用硅胶、Sephadex LH-20等色谱分离技术分离纯化羊角拗茎乙醇提取物的乙酸乙酯萃取物中的化合物,通过质谱和核磁共振等波谱技术对其结构进行鉴定,确定出了13个化合物,包括常春藤皂苷元(1)、(-)-loliolide(2)、(3S,5R,6S,7E)-3,5,6-trihydroxy-7-megastigmen-9-one(3)、(3R,6R,7E)-3-hydroxy-4,7-megastigmadien-9-one(4)、松脂素(5)、表松脂素(6)、4,4′-dihydroxy-3,3′-dimethoxybenzophenone(7)、6-羟基柚皮素(8)、东莨菪素(9)、6-羟基-7,8-二甲氧基香豆素(10)、吲唑(11)、香草酸(12)、对羟基苯甲酸(13)。其中化合物1～4和6～13为首次从羊角拗中分离得到。采用LPS诱导小鼠单核巨噬细胞RAW 264.7体外细胞炎症模型测试结果表明,化合物5能显著抑制NO的产生,IC₅₀值为18.09±1.09μM。     

C(15) Acetogenins from the red alga Laurencia obtusa.

Four C(15) acetogenins, 13-epilaurencienyne (3Z) (1), 13-epipinnatifidenyne (3E) (2), (3E, 6S(*), 7R(*), 9S(*), 10S(*), 12R(*))-9-chloro-13-bromo-6:12-epoxy-7, 10-diacetoxypentadec-3-en-1-yne (3), (3Z, 6S(*), 7R(*), 9S(*), 10S(*), 12R(*))-9-chloro-13-bromo-6:12-epoxy-7, 10-diacetoxypentadec-3-en-1-yne (4), along with the known 13-epilaurencienyne (3E) (5), have been isolated from the organic extract of the red alga Laurencia obtusa, collected in the Aegean Sea, Greece. The structures of the new natural products, as well as their relative stereochemistry, were established by means of spectral data analysis, including 2D NMR spectroscopic experiments. Some of the new metabolites exhibited significant insecticidal activity.     

Extractive compounds of betulaceae family birch buds (Betula pendula Roth.): IV. Composition of sesquiterpene diols, triols, and flavonoids

This report is devoted to study of the hydrocarbon composition of the extract of buds of birch (family Betulaceae). We identified 3,5-dihydroxy-7,4??-dimethoxyflavone, 5,7-dihydroxy-3,4??-dimethoxyflavone, 7-methoxy-4??,5-dihydroxyflavanone, 4??-methoxy-5,7-hydroxyflavanone, 5??,6??-dihydroxycaryophyllen-4(14),8(15)-diene ((1R,5R,6R,9S)-5,6-dihydroxy-11,11-dimethyl-4,8-methylenebicyclo[7.2.0]-undecane), 5??,6??-dihydroxycaryophyllen-3,8(15)-diene ((1R,5R,6R,9S)-5,6-dihydroxy-11,11-dimethyl-8-methylenebicyclo[7.2.0]undec-3-ene), 6??,9??-dihydroxy-??-humulene((1E,4E,6R,9S)-6,9-dihydroxy-4,11,11-trimethyl-8-methylene-1,4-cycloundecanediene), 5??,6??,8??-trihydroxycariolan, and (1R,5R,6R,8R,9S)-trihydroxycariolan. The gas chromatographic retention indices of all identified compounds were determined.     

肋果茶中的萜类化学成分研究

从肋果茶(Sladenia celastrifolia)95％乙醇提取物的乙酸乙酯部位中分离得到15个萜类化合物,经波谱学方法分别鉴定为sladeniafolin A(1),grasshopper ketone (2),(3S,5R,6S,7E,9R) -7-megastigmene-3,6,9-triol (3),hedytriol (4),(3S,5R,6R,7E,9R) -3,5,6,9-tetrahydroxy-7-megastigmene(5),1′S*,4′R*-8-(4′-hydroxy-2′,6′,6′-trimethylcyclohex-2-enyl)-6-methyloct-3E,5E,7E-trien -2-one (6),2α,3α,19α,23-tetrahydroxyurs-12-en-28-oic acid (7),2α,3β,19α,23-tetrahydroxyurs-12-en-28-oic acid(8),pomolic acid(9),3-O-acetyl pomolic acid(10),ursaldehyde (11),camarolide (12),3β-hydroxyurs-11-en-13β(28) -olide (13),3β-hydroxy -11α,12α-epoxy-urs-13β,28-olide (14)和28-0-β-D-glucopyranosyl euscaphic acid (15).以上化合物均首次从该植物中分离得到,其中1为新的C9裂环烯醚萜.     

New synthesis of the (3Z,6Z,9S,10R)-isomers of 9,10-epoxy-3,6-henicosadiene and 9,10-epoxy-1,3,6-henicosatriene, pheromone components of the female fall webworm moth, Hyphantria cunea

(3Z,6Z,9S,10R)-9,10-Epoxy-3,6-henicosadiene (1) and (3Z,6Z,9S,10R)-9,10-epoxy-1,3,6-henicosatriene (5), pheromone components of the female fall webworm moth (Hyphantria cunea Drury), were synthesized by starting from (2S,3R)-2,3-epoxy-4-t-butyldimethylsilyloxy-1-butanol (8). Epoxide 8 was prepared by employing lipase-catalyzed asymmetric acetylation of (+/-)-8 as the key optical resolution step.     

南海柳珊瑚鳞海底柏化学成分的研究

本文对南海柳珊瑚鳞海底柏Melitodes squarnata Nutting进行了化学成分的研究.通过用工业乙醇:二氯甲烷(2∶1)进行了提取,采用硅胶柱色谱、Sephadex LH-20凝胶色谱、高效液相半制备色谱和薄层制备等方法对鳞海底柏的化学成分进行了分离,并利用波谱分析技术和文献对照鉴定其结构.从鳞海底柏中分离得到了17个化合物,分别鉴定为:malonganenone E(1),malonganenone D(2),nuttingin A(3),腺嘌呤核苷(4),1,3,7-三甲基黄嘌呤(5),2'-脱氧胸腺嘧啶核苷(6),3-甲基-6-次黄嘌呤(7),2'-脱氧尿苷(8),(22E,24R)-ergosta-8 (14),22-dien-3β,5α,6β,7α-tetrol(9),(22E)-胆甾-5,22-二烯-3β-醇(10),胆甾醇(11),(2S,3S,4R)-N-hexadecanoyl-2-amino-1,3,4-eicosanetriol( 12),(2S,2'R,3R,4E,8E)-N-2'- Hydroxytetradecanoyl-2-amino-9-methyl-4,8-octadecaa-diene-1,3-diol(13),鲨肝醇(14),十六烷基甘油醚(15),三油酸甘油酯(16)和4-hydroxy-2,3-dimetlhy1-2-nonen-4-olide(17).     

Design,synthesis, and biological evaluation of a series of beta-lactam-based prodrugs

By use of pro-dual-drug concept the synthesis of 6-beta-[(R)-2-(clavaminio-9-N-yl)-2-(4-hydroxyphenylacetamido)]penicillanic acid (10), 6-beta-[(R)-2-(amino)-2-(4-(clavulano-9-O-yl)phenylacetamido)]penicillanic acid (13), (Z)-4-[2-(amoxycillin-4-O-yl)ethylidene]-2-(clavulano-9-O-yl)-3-methoxy-Delta(alpha,beta)-butenolide (19), and 3-[(amoxicillin-4-O-yl)methyl]-7-(phenoxyacetamido)-(1-oxo)-3-cephem-4-carboxylic acid (23) was accomplished. Unlike penicillin G, ampicillin, or amoxicillin, these four heretofore undescribed compounds 10, 13, 19, and 23 showed notable activity against beta-lactamase (betaL) producing microorganisms, Staphylococcus aureus A9606, S. aureus A15091, S. aureus A20309, S. aureus 95, Escherichia coli A9675, E. coli A21223, E. coli 27C7, Pseudomonas aeruginosa 18S-H, and Klebsiella pneumoniae A20634 TEM. In comparison with amoxicillin (9), alpha-amino-substituted compound 10 and butenolide derivative 19 showed a broadened spectrum of antibacterial activity; yet they were found to be less active than 13 and 23. Like clavulanic acid (7) or cephalosporin-1-oxide (21), the newly synthesized compounds 10, 13, 15, 16, 19, or 23 functioned as potent inhibitors of various bacterial betaLs.     

New sugars from antigenic lipopolysaccharides of bacteria: identification and synthesis of 3-O-[(R)-1-carboxyethyl]-L-rhamnose, an acidic component of Shigella dysenteriae type 5 lipopolysaccharide.

A new acidic sugar, 3-O-[(R)-1-carboxyethyl]-L-rhamnose (1), has been identified as a constituent of the O-antigenic lipopolysaccharide of Sh. dysenteriae type 5. The structure of 1 has been established by physico-chemical methods and by synthesis. Alkylation of methyl 2,5-di-O-benzyl-alpha-L-rhamnofuranoside (6) with (S)- or (R)-2-chloropropionic acids, followed by removal of the protecting groups, afforded 3-O-[(R)-1-carboxyethyl]-L-rhamnose (9) and 3-O-[(S)-1-carboxyethyl]-L-rhamnose (10), respectively. The properties of 1 coincide with those of 9.     

Model platinum nucleobase and nucleoside complexes and antitumor activity: X-ray crystal structure of [PtIV(trans-1R,2R-diaminocyclohexane)trans-(acetate)2(9-ethylguanine)Cl]NO3.H2O

A series of platinum(II) and (IV) monoadducts of the type [Pt(II)(DACH)LCl]NO3 and [Pt(IV)(DACH)trans-(X)2LCl]NO3 (where DACH=trans-1R,2R-diaminocyclohexane, L=adenine, guanine, hypoxanthine, cytosine, adenosine, guanosine, inosine, cytidine, 9-ethylguanine (9-EtGua), or 1-methylcytosine and X=hydroxo or acetato ligand) have been synthesized and characterized by elemental analysis and by 1H and 195Pt nuclear magnetic resonance (NMR) spectroscopy. The crystal structure of the model nucleobase complex [Pt(IV)(trans-1R,2R-diaminocyclohexane)trans-(acetate)2(9-EtGua)Cl]NO3.H2O was determined using a single crystal X-ray diffraction method. The compound crystallized in the monoclinic space group P2(1), with a=10.446(2) A, b=22.906(5) A, c=10.978(2) A, Z=4, and R=0.0718, based upon the total of 11,724 collected reflections. In this complex, platinum had a slightly distorted octahedron geometry owing to the presence of a geometrically strained five-member ring. The two adjacent corners of the platinum plane were occupied by the two amino nitrogen of DACH, whereas, the other two equatorial positions occupied by chloride ion and 9-ethylguanine. The remaining two axial positions were occupied by the oxygen atoms of acetato ligands. The DACH ring was in a chair configuration. An intricate network of intermolecular hydrogen bonds held the crystal lattice together. Some of these synthesized models of DACH-Pt-DNA adducts have good in vitro cytotoxic activity against the cisplatin-sensitive human cancer ovarian A2780 cell line (IC50=1-8 microM). Interestingly, a substituted nucleobase (9-ethylguanine) adduct was over 6-fold more potent than regular adducts. The cross-resistance factor against the 44-fold cisplatin-resistant 2780CP/clone 16 cells was about 3-9; thus, the cytotoxicity of adducts was indicative of low potency, but the resistance factors were also substantially low. These results suggest that DNA adducts of DACH-Pt are cytotoxic with low cross-resistance.     

Reactivity pathways for nitric oxide and nitrosonium with iron complexes in biologically relevant sulfur coordination spheres

The interaction of nitric oxide (NO) with iron-sulfur cluster proteins results in the formation of dinitrosyl iron complexes (DNICs) coordinated by cysteine residues from the peptide backbone or with low molecular weight sulfur-containing molecules like glutathione. Such DNICs are among the modes available in biology to store, transport, and deliver NO to its relevant targets. In order to elucidate the fundamental chemistry underlying the formation of DNICs and to characterize possible intermediates in the process, we have investigated the interaction of NO (g) and NO(+) with iron-sulfur complexes having the formula [Fe(SR)(4)](2-), where R=(t)Bu, Ph, or benzyl, chosen to mimic sulfur-rich iron sites in biology. The reaction of NO (g) with [Fe(S(t)Bu)(4)](2-) or [Fe(SBz)(4)](2-) cleanly affords the mononitrosyl complexes (MNICs), [Fe(S(t)Bu)(3)(NO)](-) (1) and [Fe(SBz)(3)(NO)](-) (3), respectively, by ligand displacement. Mononitrosyl species of this kind were previously unknown. These complexes further react with NO (g) to generate the corresponding DNICs, [Fe(SPh)(2)(NO)(2)](-) (4) and [Fe(SBz)(2)(NO)(2)](-) (5), with concomitant reductive elimination of the coordinated thiolate donors. Reaction of [Fe(SR)(4)](2-) complexes with NO(+) proceeds by a different pathway to yield the corresponding dinitrosyl S-bridged Roussin red ester complexes, [Fe(2)(mu-S(t)Bu)(2)(NO)(4)] (2), [Fe(2)(mu-SPh)(2)(NO)(4)] (7) and [Fe(2)(mu-SBz)(2)(NO)(4)] (8). The NO/NO(+) reactivity of an Fe(II) complex with a mixed nitrogen/sulfur coordination sphere was also investigated. The DNIC and red ester species, [Fe(S-o-NH(2)C(6)H(4))(2)(NO)(2)](-) (6) and [Fe(2)(mu-S-o-NH(2)C(6)H(4))(2)(NO)(4)] (9), were generated. The structures of 8 and 9 were verified by X-ray crystallography. The MNIC complex 1 can efficiently deliver NO to iron-porphyrin complexes like [Fe(TPP)Cl], a reaction that is aided by light. Removal of the coordinated NO ligand of 1 by photolysis and addition of elemental sulfur generates higher nuclearity Fe/S clusters.     

Chemical Constituents of Schisandra rubriflora Rehd.et Wils.

Schisandra rubriflora Rehd. et Wils. is a traditional Chinese medicine. To search for new and bioactive components from traditional Chinese medicines and provide scientific evidence for taxonomy, the chemical constituents ofthe plant were investigated by various column chromatography methods (silica gel,Sephadex LH-20, and RP-18). From the aerial parts ofS. rubriflora, three new megastigmane glycosides,namely (3S, 5R, 6S, 9R)-megastigmane-3, 9-diol 3-O-[α-L-arabionfuranosyl-(1→6)-β-D-glucopyranoside](1), 7-megastigmene-3-ol-9-one 3-O-[o-L-arabionfuranosyl-(1→6)-β-D-glucopyranoside] (2), and megastigmane-3α, 4β, 9ξ-triol 3-O-β-D-glucopyranoside (3), along with 14 known compounds, were isolated.The structures of the new compounds were elucidated by a combination of spectroscopic and chemical methods.     

A novel phytotoxic nonenolide from Phomopsis sp. HCCB03520

A novel phytotoxic nonenolide, (6S,7R,9R)-6,7-dihydroxy-9-propylnon-4-eno-9-lactone (1), was isolated from solid cultures of the endophytic fungus Phomopsis sp. HCCB03520, together with three known compounds, cytochalasin H (2), cytochalasin N (3), and epoxycytochalasin H (4). The structures of these compounds were elucidated through spectroscopic analysis, and the absolute configurations were determined by CD spectroscopy. Phytotoxic activities of compounds 1-4 were also investigated. Compound 1 showed phytotoxic activity on germination and radicle growth of Medicago sativa, Trifolium hybridum, and Buchloe dactyloides.     

Computer aided screening and evaluation of herbal therapeutics against MRSA infections

Methicillin resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life threatening outbreaks such as community-onset and nosocomial infections has emerged as 'superbug'. The organism developed resistance to all classes of antibiotics including the best known Vancomycin (VRSA). Hence, there is a need to develop new therapeutic agents. This study mainly evaluates the potential use of botanicals against MRSA infections. Computer aided design is an initial platform to screen novel inhibitors and the data finds applications in drug development. The drug-likeness and efficiency of various herbal compounds were screened by ADMET and docking studies. The virulent factor of most of the MRSA associated infections are Penicillin Binding Protein 2A (PBP2A) and Panton-Valentine Leukocidin (PVL). Hence, native structures of these proteins (PDB: 1VQQ and 1T5R) were used as the drug targets. The docking studies revealed that the active component of Aloe vera, β-sitosterol (3S, 8S, 9S, 10R, 13R, 14S, 17R) -17- [(2R, 5R)-5-ethyl-6-methylheptan-2-yl] -10, 13-dimethyl 2, 3, 4, 7, 8, 9, 11, 12, 14, 15, 16, 17- dodecahydro-1H-cyclopenta [a] phenanthren-3-ol) showed best binding energies of -7.40 kcal/mol and -6.34 kcal/mol for PBP2A and PVL toxin, respectively. Similarly, Meliantriol (1S-1-[ (2R, 3R, 5R)-5-hydroxy-3-[(3S, 5R, 9R, 10R, 13S, 14S, 17S)-3-hydroxy 4, 4, 10, 13, 14-pentamethyl-2, 3, 5, 6, 9, 11, 12, 15, 16, 17-decahydro-1H-cyclopenta[a] phenanthren-17-yl] oxolan-2-yl] -2- methylpropane-1, 2 diol), active compound in Azadirachta indica (Neem) showed the binding energies of -6.02 kcal/mol for PBP2A and -8.94 for PVL toxin. Similar studies were conducted with selected herbal compound based on pharmacokinetic properties. All in silico data tested in vitro concluded that herbal extracts of Aloe-vera, Neem, Guava (Psidium guajava), Pomegranate (Punica granatum) and tea (Camellia sinensis) can be used as therapeutics against MRSA infections.     

Synthesis, lipophilicity and anti-HIV activity of a new brominated analog of zidovudine.

A novel cyclic bromine zidovudine analog, (-)-trans-(5S,6S)-5-bromo-6,5'- epoxy-5,6-dihydro-3'-azido-3'-deoxythymidine (2), and its diastereoisomer (+)-trans-(5R,6R)-(3) were synthesized and characterized by spectroscopic methods, obtaining 3 in very low yields. The major product 2 presents a selectivity index (CCID50/IC50) similar to zidovudine but 55.5 times with higher lipophilicity, which should increase the ability of 2 to cross the blood-brain barrier by a non facilitated diffusion mechanism.     

黄瓜藤的化学成分研究

从丽江产黄瓜藤甲醇提取物的氯仿部位分离得到9个化合物,经理化和波谱分析鉴定为α-菠甾醇(1)、α-菠甾醇-3-O-β-D-葡萄糖苷(2)、β-谷甾醇(β-sitosterol,3)、豆甾-7-烯-3-O-β-D-葡萄糖苷(4)、22-亚甲基-9,19-环羊毛甾烷-3β-醇(5)、(2S,3S,4R,10E)-2-(2′,3′-二羟基二十四烷酰氨基)-10-十八烯-1,3,4-三醇(6)、(2S,3S,4R,10E)-2-[(2′R)-2-羟基二十四烷酰氨基]-10-十八烯-1,3,4-三醇(7)、(2S,3S,4R,10E)-1-(β-D-葡萄糖苷)-2-[(2′R)-2-羟基二十四烷酰氨基]-10-十八烯-1,3,4-三醇(8)、大豆脑苷(9),除化合物3外,其它化合物均为首次从该植物中分离得到.     

Cellular Mechanisms of Protection by Metabotropic Glutamate Receptors During Anoxia and Nitric Oxide Toxicity

Abstract: Metabotropic glutamate receptors, nitric oxide (NO), and the signal transduction pathways of protein kinase C (PKC) and protein kinase A (PKA) can independently alter ischemic-induced neuronal cell death. We therefore examined whether the protective effects of metabotropic glutamate receptors during anoxia and NO toxicity were mediated through the cellular pathways of PKC or PKA in primary hippocampal neurons. Pretreatment with the metabotropic glutamate receptor agonists (±)-1-aminocyclopentane- trans -1,3-dicarboxylic acid, (1 S ,3 R )-1-aminocyclopentane-1,3-dicarboxylic acid (1 S ,3 R -ACPD), and l (+)-2-amino-4-phosphonobutyric acid ( l -AP4) 1 h before anoxia or NO exposure increased hippocampal neuronal cell survival from ∼30 to 70%. In addition, posttreatment with 1 S ,3 R -ACPD or l -AP4 up to 6 h following an insult attenuated anoxic- or NO-induced neurodegeneration. In contrast, treatment with l -(+)-2-amino-3-phosphonopropionic acid, an antagonist of the metabotropic glutamate receptor, did not significantly alter neuronal survival during anoxia or NO exposure. Protection by the ACPD-sensitive metabotropic receptors, such as the subtypes mGluR1α, mGluR2, and mGluR5, appears to be dependent on the modulation of PKC activity. In contrast, l -AP4-sensitive metabotropic glutamate receptors, such as the subtype mGluR4, may increase neuronal survival through PKA rather than PKC. Thus, activation of specific metabotropic glutamate receptors is protective during anoxia and NO toxicity, but the signal transduction pathways mediating protection differ among the metabotropic glutamate receptor subtypes.     

Chemical Constituents of Schisandra rubriflora Rehd. et Wils.

Schisandra rubriflora Rehd. et Wils. is a traditional Chinese medicine. To search for new and bioactive components from traditional Chinese medicines and provide scientific evidence for taxonomy, the chemical constituents of the plant were investigated by various column chromatography methods (silica gel, Sephadex LH-20, and RP-18). From the aerial parts of S. rubriflora, three new megastigmane glycosides,namely (3S, 5R, 6S, 9R)-megastigmane-3, 9-diol 3-O-[α-L-arabionfuranosyl-(1→6)-β-D-glucopyranoside](1), 7-megastigmene-3-ol-9-one 3-O-[α-L-arabionfuranosyl-(1→6)-β-D-glucopyranoside] (2), and megastigmane-3α, 4β, 9ξ-tfiol 3-O-β-D-glucopyranoside (3), along with 14 known compounds, were isolated.The structures of the new compounds were elucidated by a combination of spectroscopic and chemical methods.     

Stereochemistry of megastigmane glucosides from Glochidion zeylanicum and Alangium premnifolium

From Glochidion zeylanicum, two megastigmane glucosides, 3- and 9-O-beta-D-glucopyranosides of (3S,5R,6R,7E,9S)-megastigman-7-ene-3,5,6,9-tetrol (1 and 2, respectively), were isolated. Their structures were different from those of kiwiionoside (3) and actinidioionoside (4), isolated from Actinidia chinensis and Actinidia polygama, respectively, in the stereochemistry at the 9-positions. Alangionosides E (5) and O (6), isolated from the leaves of Alangium premnifolium, are also megastigmane glucosides, and the latter is closely related to 1 and actinidioionoside (4). However, the absolute configurations of the 9-position remained to be determined. They were analyzed to be R by means of a modified Mosher's method. Alangionoside E (5) is identical with corchoionoside A in all aspects. The name of corchoionoside A must be retained thereafter.