A Novel Flavonoid Glucoside from Anoectochilus roxburghii （Wall,） Lindl.

Eight compounds were isolated from the ethyl acetate- and n-butanol-soluble fractions of the ethanollc extract of the whole plant of Anoectochllus roxburghll（Wali.） Lindi. （Orchidaceee）. On the basis of spectroscopic methods, the structures of these compounds were elucidated as quercetin-7-O-β-D-[6＂-O-（trans-feruloyi）]- giucopyranosids （compound 1）, 8-C-p-HydroxybenzyiquerceUn （compound 2）, isorhamnetin-7-O-β-D- giucopyranoside （compound 3）, isorhamnetin-3-O-β-D-giucopyranoside （compound 4）, kaempferoi-3-O-β-D- giucopyranoside （compound 5）, kaempferoi-7-O-β-D-giucopyranoside （compound 6）, 5-hydroxy-3＇,4＇,7- trimethoxyfiavonoi-3-O-β-D-rutinoside （compound 7）, and isorhamnetin-3-O-β-D-rutinoside （compound 8）. Of the compounds isoisted, compound 1 was a new flavonoid giucoside and exhibited strong scavenging activity against the 1,1-diphenyi-2-picryihydrazyi free radical, whereas the ethanolic extract showed weak activity. Compounds 2-8 were obtained from this family for the first time.     

Chemical Constituents of Daphne giraldii Nitsche

In a search for structurally interesting substances from traditional Chinese medicines, eight compounds were isolated from an ethanolic extract of the stem bark of Daphne giraldii Nitsche. On the basis of one- and two-dimensional nuclear magnetic resonance and mass spectrometry data, and chemical methods, their structures were determined to be 2H-1-benzopyran-2-one-8-hydroxy-7-O-β-D-glucopyranosyl-5-（2-oxo- 2H-1-benzopyran-7-hydroxy-8-yloxy） （compound 1）, 1-pentanone, 1-（4-hydroxyphenyl）-5-phenyl （compound 2）, octadecyl caffeate （compound 3）, （＋）syringaresinol-4,4＇-diglycoside （compound 4）, daphnetin-8-O-β-D- glucopyranoside （compound 5）, p-hydroxybenzoic acid （compound 6）, 7,7＇-dihydroxy-[6, 8＇-bi-2H-benzopyran]- 2, 2＇-dione （compound 7）, and daphnorin （compound 8）, respectively. Of the compounds isolated, compounds 1 and 2, which we named daphnolin and daphnolon, respectively, were new, and the others were obtained from this plant for the first time.     

珠子草化学成分的研究

利用大孔树脂吸附和多种柱层析方法,从珠子草中分离得到5个化合物,根据理化数据和波谱学等方法鉴定为柯里拉京(1)、芦丁(2)、isobubbialine(3)、丁二酸(4)和没食子酸(5)。根据2D-NMR修正了化合物3的部分碳信号归属,归属了化合物1的碳氢谱数据。     

A substituted 3,4-dihydropyrimidinone derivative (compound D22) prevents inflammation mediated neurotoxicity; role in microglial activation in BV-2 cells

A novel synthetic 3,4-dihydropyrimidinone derivative, compound D22 (ethyl 6-methyl-4-(3-phenoxyphenyl)-2-thioxo-3,4-dihydropyrimidine-5-carboxylate), was found to exert anti-inflammatory properties in lipopolysaccharide-stimulated microglial BV-2 cells. Compound D22 reduced the pro-inflammatory factors such as nitric oxide, prostaglandin E(2), tumor necrosis factor-α and interleukin-1β. Moreover, it suppressed the expressions of inducible NO synthase and cyclooxygenase-2. Compound D22 inhibited the activation of mitogen-activated protein kinases. When compound D22-conditioned media from BV-2 cells were applied to N2a cells, neuronal cell death was inhibited via suppression of caspase-3 activation and regulation of Bcl-2 and Bax proteins expression. These results suggest that compound D22 may be useful for treating neurodegenerative diseases related with neuroinflammation.     

A New Prenylated Flavonoid from Propolis Collected in Okinawa,Japan

The new prenylflavonoid, isonymphaeol-B (1), together with three known compounds, nymphaeol-A (2), nymphaeol-B (3), and nymphaeol-C (4), were isolated from propolis collected in Okinawa, the southern-most prefecture of Japan. The structure of each compound was determined by spectral methods, including mass spectrometry and 2D NMR. Each compound had 1,1-diphenyl-2-picryl-hydrazyl radical-scavenging activity.     

A new prenylated flavonoid from propolis collected in Okinawa, Japan

The new prenylflavonoid, isonymphaeol-B (1), together with three known compounds, nymphaeol-A (2), nymphaeol-B (3), and nymphaeol-C (4), were isolated from propolis collected in Okinawa, the southern-most prefecture of Japan. The structure of each compound was determined by spectral methods, including mass spectrometry and 2D NMR. Each compound had 1,1-diphenyl-2-picryl-hydrazyl radical-scavenging activity.     

Iridoid Glycosides from Pedicularis dolichocymba Hand.-Mazz.

During investigation of the chemical constituents of the whole plant ethanol extract of Pedlcularis dollchocymba Hand.-Mazz. （Scrophularlaceae）, four new irldold glycosides, dolichocymbosides A （compound 1）, B （compound 2）, C （compound 3） and D （compound 4）, were Isolated. Their structures were determined based on spectral data Including 1D and 2D-nuclear magnetic resonance spectroscopy （^1H-^1H COSY, HSQC, HMBC, ROESY） and FAB-MS.     

Synthesis and biological characterization of 1alpha,24,25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (24-hydroxylated ED-71)

24-Hydroxylated derivatives were synthesized in 24(R) and 24(S) forms by the convergent method as analogs related to 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3). In the convergent synthesis, the A-ring fragment, synthesized from diethyl D-tartarate, and the C/D-ring fragments in 24(R) and 24(S) forms (vitamin D numbering), obtained from vitamin D(2) via the Inhoffen-Lythgoe diol, were coupled in moderate yields to give 1alpha,24(R),25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) and 1alpha,24(S),25-trihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3). In preliminary biological evaluations, 24-hydroxylation of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) caused weakened affinity to vitamin D binding protein in vitro and less calcemic activity in vivo compared to the parent compound. While the affinity to vitamin D receptor in 24(R) epimer was sustained, the affinity in 24(S) epimer was less than that of the parent compound.     

Phialomyces macrosporus: Chemical Constituents,Antimicrobial Activity and Complete NMR Assignments for the 7,7′‐Biphyscion

Five known secondary metabolites, chrysophanol ( 1 ), 7,7′‐biphyscion ( 2 ), secalonic acid D ( 3 ), mannitol ( 4 ) and trehalose ( 5 ) were isolated for the first time from the extracts of the fungus Phialomyces macrosporus. Their structures were elucidated by NMR methods (1D and 2D NMR analysis), optical activity and ESI‐MS. Complete ¹H and ¹³C assignments were performed for compound 2 . The antimicrobial activity was evaluated by serial microdilution assay for compounds 2 and 3 and results showed that compound 3 exhibited a significant growth inhibition at concentrations of 15.6 mg/ml (S. aureus and S. choleraesius) and 0.97 mg/mL (B. subtilis), comparable to the positive control.     

海藻中两种纤溶活性化合物的分离与结构鉴定

采用氯仿-甲醇有机溶剂提取、常压硅胶柱层析等方法进行分离纯化,从微劳马尾藻的提取物中分离纯化了6个化合物;根据核磁共振谱分析及文献解析化合物B、D分别确定为棕榈酰基．油酰基-3-O-α-D-吡喃葡萄糖基甘油和肉豆蔻酰基-油酰基-3-O-α-D-吡喃葡萄糖基甘油;使用酶标仪体外测定化合物的纤溶活性,发现化合物B使纤溶作用提高了10％～30％,化合物D的纤溶促进作用弱于化合物B;分离纯化的纤溶促进化合物B和D属于甘油糖脂类化合物。本文首次从微劳马尾藻分离得到了肉豆蔻酰基．油酰基-3-O-α-D-吡喃葡萄糖基甘油。     

Studies on the Triterpenes of Terminalia chebula Retz.

Four triterpenes have been isolated from the alcoholic extract of Terminalia Chebula Retz.. Three of them have been identified as terminoic acid (T1), arjugenin (T2) and arjunolic acid(T3). T4 is a new compound, named chebupentol. Its structure was established to be olean-12-ene-2,3,19,23,28-pentol on the basis of its IR, MS, 1HNMR, 13CNMR, 1H-13C 2D NMR, 1H-1H 2D NMR and NOESY 2D NMR. The structure of compound T4 was confirmed by the chemical transformation of T4 from arjugenin (T2) with LiAlH4.     

Polyketides from Penicillium sp. JP-1, an endophytic fungus associated with the mangrove plant Aegiceras corniculatum

Four polyketides, leptosphaerone C (1), penicillenone (2), arugosin I (3) and 9-demethyl FR-901235 (4), as well as five known compounds, bacillosporin A (5), bacillosporin C (6), sequoiamonascin D (7), sequoiatone A (8), and sequoiatone B (9) were isolated from the Penicillium sp. JP-1, an endophytic fungus isolated from Aegiceras corniculatum. Their structures were determined by spectroscopic methods, mainly by 2D NMR spectroscopic analyses. Compound 1 showed cytotoxicity against A-549 cells with an IC50 value of 1.45 microM, while compound 2 showed cytotoxicity against P388 cells with an IC50 value of 1.38 microM.     

Lactones from a brown alga endophytic fungus (No. ZZF36) from the South China Sea and their antimicrobial activities

Two new metabolites named 6-oxo-de-O-methyllasiodiplodin (1) and (E)-9-etheno-lasiodiplodin (2), with three known compounds lasiodiplodin (3), de-O-methyllasiodiplodin (4), and 5-hydroxy-de-O-methyllasiodiplodin (5), were isolated from the mycelium extracts of a brown alga endophytic fungus (No. ZZF36) obtained from the South China Sea. Their structures were elucidated using spectroscopic methods, mainly 1D and 2D NMR. Additionally, the structure of compound 1 was confirmed by single crystal X-ray diffraction analysis. The antimicrobial activities of lasiodiplodins, and the 13-acetyl and 12,14-dibromo derivatives of lasiodiplodin were tested for the first time and the results were compared to each other.     

A new prenylflavonoid isolated from propolis collected in the Solomon Islands

The new prenylflavonoid, solophenol A (1), together with three known compounds, bonannione A (2), sophoraflavanone A (3) and (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone (4), were isolated from propolis collected from Malaita Island in The Solomon Islands. The structure of each compound was determined by spectroscopic methods, including mass spectrometry and 2D NMR. Compound 1 exhibited potent 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity.     

Betagamma-dehydrocurvularin and related compounds as nematicides of Pratylenchus penetrans from the fungus Aspergillus sp

The new nematicidal compound, betagamma-dehydrocurvularin (1), together with three known compounds, alphabeta-dehydrocurvularin (2), 8-beta-hydroxy-7-oxocurvularin (3) and 7-oxocurvularin (4), were isolated from the culture filtrate and mycelial mats of Aspergillus sp. The structures of 1-4 were established by spectroscopic methods including 2D NMR. The biological activities of 1-4 were examined by bioassays with root-lesion nematodes, and lettuce and rice seedlings.     

Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: selective inhibitors of dopamine D₁ receptor

A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D(1) and D(2)) and serotonin (5-HT(1A) and 5-HT(2A)) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D(1) receptor, as well as high selectivity for the D(1) receptor over the D(2), 5-HT(1A), and 5-HT(2A) receptors. Among these, compound 19c exhibited a promising D(1) receptor binding affinity (K(i)=2.53nM) and remarkable selectivity versus D(2)R (inhibition=81.87%), 5-HT(1A)R (inhibition=61.70%), and 5-HT(2A)R (inhibition=24.96%). Compared with l-(S)-stepholidine (l-SPD) (D(1)K(i)=6.23nM, D(2)K(i)=56.17nM), compound 19c showed better binding affinity for the D(1) receptor (2.5-fold higher) and excellent D(2)/D(1) selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D(1) receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D(1) receptor. These results are in accord with molecular docking studies.     

Cyclopeptidic Constituents from Arenaria oreophila J. D. Hooker （Caryophyllaceae）

To further investigate the cyclopeptldes of the Caryophyllaceae family, two new cyclopeptldes, named Arenarlphilin E （compound 1） and Arenariphilin F （compound 2）, were obtained from Arenaria oreophUe J. D. Hooker using some Isolation methods, e. g. normal and reverse silica gel. By detailed spectroscopic analysis, such as FAB^＋-MS, 1 D NMR, 2D NMR, the structures of Arenariphilin E （compound 1） and Arenariphilln F （compound 2） were determined as cyclo（lle^1-Gly-Val^1-Ala-Leu-lle^3-lle^2-Val^2-Pro） and cyclo（Pro^2-Pro^1-Gly^2-lle-Val-Leu-Gly^1-AiaThr- Gly^3）, respectively.     

Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines

A series of apomorphine ((-)-1, APO)-derived analogues ((+/-)-3, (-)-4-(-)-6) were designed and synthesized by hybridizing APO with a privileged 2-aminothiazole functionality which was lent from the orally available anti-parkinsonian drug, pramipexole (2). Among these hybridized compounds, catecholic aporphine (-)-6 shows good affinity at the D(2) receptor with K(i) of 328nM, slightly less potent (3-fold), but more selective against the D(1) receptor than that of the parent compound, APO. Although possessing reduced affinity at the D(2) receptor, aporphines 15 and 18 show significant potency at both the D(1) and 5-HT(1A) receptors. The former compound is equipotent at both receptors (K(i): 116 and 151nM, respectively), while the latter is 8-fold more potent at the D(1) (K(i): 78nM) than at the 5-HT(1A) receptors (K(i): 640nM). These results indicate that the catechol fragment is critical for the D(2) receptor binding of the anti-parkinsonian drug, APO ((-)-1), but not necessary for binding at the D(1) and 5-HT(1A) receptors.     

Role of axial ligands in the reactivity of Mn peroxidase from Phanerochaete chrysosporium.

Site-directed mutagenesis was performed on Mn peroxidase (MnP) from the white-rot fungus Phanerochaete chrysosporium to investigate the role of the axial ligand hydrogen-bonding network on heme reactivity. D242 is hydrogen bonded to the proximal His of MnP; in other peroxidases, this conserved Asp, in turn, is hydrogen bonded to a Trp. In MnP and other fungal peroxidases, the Trp is replaced by a Phe (F190). Both residues are thought to have a direct influence on the electronic environment of the catalytic center. To study only the active mutants at D242 and F190, we used degenerate oligonucleotides allowing us to screen all 19 possible amino acid mutants at these positions. Two mutants at D242 passed our screen, D242E and D242S. Both mutations impaired only the functioning of compound II. The reactions of the ferric enzyme with H(2)O(2) were unaffected by the mutations, as were the reactions of compound I with reducing substrates. The D242S and D242E mutations reduced the first-order rate constant for the reaction of MnP compound II with chelated Mn(2+) from 233 s(-1) (wild type) to 154 s(-1) and 107 s(-1), respectively. Three F190 mutants passed our screen, F190V, F190L, and F190W. Similar to mutants at D242, these mutants largely affected the function of compound II. The F190V mutation increased the first-order rate constant for the reduction of compound II by chelated Mn(2+) to 320 s(-1). The F190L mutation decreased this rate to 137 s(-1). The F190W mutant was not very stable, but at pH 6.0, this mutation decreased the rate of compound II reduction by Mn(2+) from 140 s(-1) in the wild type to 36 s(-1). There was no indication that the F190W mutant was capable of forming a protein-centered Trp cation radical. All the mutations altered the midpoint potential of the Fe(3+)/Fe(2+) couple of the enzyme, as calculated from cyclic voltammagrams of the proteins. The values were shifted from -96 mV in the wild-type enzyme to -123 mV in D242S, -162 mV in D242E, -82 mV in F190L, -173 mV in F190V, and -51 mV in F190W. Collectively, these results demonstrate that D242 and F190 in MnP influence the electronic environment around the heme and that the reactions of compound II are far more sensitive to this influence than the reduction of compound I.     

Anthracycline metabolites of tetracenomycin C-nonproducing Streptomyces glaucescens mutants.

Mutants of Streptomyces glaucescens GLA.0 which are blocked in the production of tetracenomycin C (compound 1), an anthracycline antibiotic having significant antitumor activity, accumulated several new anthracycline metabolites structurally related to compound 1 and to intermediates of its biosynthetic pathway. Through chemical and spectroscopic comparisons with the known anthracycline metabolites of the wild-type strain, we identified the two regioisomers of tetracenomycin B2 (compounds 7a and 7b), 8-demethyltetracenomycin C (compound 12), tetracenomycin D2 (compound 11), tetracenomycin E (compound 13), and the 12-naphthacenone forms of compounds 7a, 7b, and 2 (tetracenomycin D1). A hypothetical biosynthetic pathway to compound 1 is presented that is consistent with the occurrence of compounds 7b, 13, and 5 (tetracenomycin A2) and with the cosynthetic behavior of tetracenomycin C-nonproducing mutants (H. Motamedi, E. Wendt-Pienkowski, and C. R. Hutchinson, J. Bacteriol. 167:575-580, 1986).