新型1-(1,3,5-三嗪-6-基)-3-甲基-4-(5-苯基-1,3,4-噁二唑-2-基)吡唑的合成及活性评价

设计合成了18个以吡唑桥连1,3,4-噁二唑和1,3,5-三嗪的新型多杂环分子[7A(a~f),7B(a~f)和7C(a~f)];通过红外光谱(IR)、核磁共振波谱(NMR)和高分辨质谱(HRMS)等对目标分子进行了结构表征;评价了目标分子对蛋白酪氨酸磷酸酯酶1B(PTP1B)和细胞分裂周期25磷酸酯酶B(Cdc25B)的抑制活性.结果表明,所有目标分子对PTP1B和Cdc25B均有较好的抑制活性,其中,9个目标分子表现出优异的PTP1B和Cdc25B抑制效果,IC50值低于齐墩果酸(PTP1B抑制活性测试参照物)和正钒酸钠(Cdc25B抑制活性测试阳性参照物),有望成为潜在的PTP1B和Cdc25B抑制剂.     

Three-coordinate organoboron with a B=N bond: substituent effects, luminescence/electroluminescence and reactions with fluoride

Five new three-coordinate boron compounds with a B=N bond involving an indole or a substituted indole ligand including B(mesityl)2(indolyl), (1), B(mesityl)2(2-Me-indolyl), (2), B(mesityl)2(3-Me-indolyl), (3), B(mesityl)2 (7-Me-indolyl), (4), and B(mesityl)2(3-Ph-indolyl), (5) have been synthesized. The structures of these new compounds were determined by X-ray diffraction analyses. All five compounds are luminescent involving a charge transfer transition between the indolyl pi orbital and the boron p(pi) orbital. The substituent group on the indolyl ring was found to have a subtle impact on the electronic properties of compounds. NMR experiments established that the methyl group at the 7-position of indole is most effective in blocking the rotation of the mesityl group around the B-C bond. The addition of fluoride ions to this group of compounds causes luminescent quenching and an irreversible decomposition of the compounds due to the reaction of the F- adduct with water molecules. The potential use of this group of compounds as blue emitters in electroluminescent (EL) devices was demonstrated by the successful fabrication of a four-layer EL device where 1 was used as the emitter. The EL device displays a blue emission with a maximum luminescence being 1037 cd m(-2) and a maximum current efficiency about 0.7 cd A(-1) at 5 V.     

Bioactive Trichothecenes Produced by the Myrothecium sp. QB‐1

Three new simple trichothecenes, 15‐acetyltrichoverrol B ( 3 ), 13′‐acetyltrichoverrin B ( 5 ), and 6′‐dehydroxytrichoverrin B ( 6 ), along with five known trichothecenes trichodermadienediol B ( 1 ), trichoverrol B ( 2 ), trichoverrin B ( 4 ), and roridins A ( 7 ) and D ( 8 ), have been isolated from the liquid culture of Myrothecium roridum (strain no. QB‐1). The structures of the new compounds were established by comprehensive analysis of 1D‐ and 2D‐NMR data. All the compounds were evaluated for antifungal activity, only compounds 7 and 8 showed significant antifungal activity against the tested fungi (MIC ranged from 10 to 5 μg/ml).     

Synthesis and antiviral activities of synthetic glutarimide derivatives

A series of novel glutarimide compounds were synthesized and their antiviral activities were evaluated. The compounds displaying the strongest antiviral activities included 5, 6f, 7e and 9 against coxsackievirus B3 (Cox B3), 10 and 6f against influenza virus A (influenza A) and 7a against herpes simplex virus 2 (HSV-2). However, most of the synthetic glutarimides showed comparatively much weaker activity against influenza A, Cox B3 and HSV-2 than the natural glutarimide compounds tested. Based on the results, it seemed likely that a conjugated system at the β-substituted moiety provides stronger antiviral activity.     

Phenolic glycosides and pyrrolidine alkaloids from Codonopsis tangshen

Chemical examination of the n-butanol extract of the root of Codonopsis tangshen led to the isolation of four new compounds named codonosides A (1) and B (2) and codonopyrrolidiums A (3) and B (4), with seven known compounds [(Z)-2-(beta-glucopyranosyloxy)-3-phenylpropenoic acid (5), lobetyolin (6), lobetyol (7), luteolin (8), friedelin (9), 5,6,9-trihydroxy-octadec-7-enoic acid (10), and adenosine (11)]. Based on spectroscopic evidence, the structures of codonosides A (1) and B (2) were established as phenolic glycosides, and those of codonopyrrolidiums A (3) and B (4) as pyrrolidines. The relative configuration of 3 was determined by X-ray crystallographic analysis.     

锦灯笼果实的化学成分研究

从锦灯笼中分离得到5个甾体类化合物,分别鉴定为酸浆素A(1,alkekengilin A)、酸浆素B(2,alkekengilin B)、酸浆苦素D(3,physalin D)、酸浆苦素P(4,physalin P)、4,7-二去氢新酸浆苦素B(5,4,7-didehydro-neophysalin B).其中酸浆素A(1,alkekengilin A)和酸浆素B(2,alkekengilin B)为新的天然产物.运用现代波谱技术对上述化合物的结构进行了确证.     

Allylic-type diindium reagents. Reactivity toward electrophiles and cascade coupling reactions with imines

The allylic-type diindium reagents A and B were prepared from 3-bromo-1-iodopropene (1a) and 4-bromo-2-iodobut-2-ene (1b), respectively, and their reactions with electrophiles were investigated. The diindium reagents A and B were initially reacted with imines and the resulting vinylindium compounds were then treated with organic halides in the presence of Pd(PPh(3))(4) to give linear N-aryl and N-tosyl homoallylic amines. Diindium A is stable in a small amount of water in solvent, whereas B is easily protonated to give a crotylindium reagent. The reaction of B with benzaldehyde gives mainly the 1,3- and 1,5-diols via a spontaneous coupling with two molecules of the aldehyde, in contrast to A, which reacts with one molecule of carbonyl compounds to give the vinylindium compounds.     

金丝矮陀陀植物中甾体生物碱的分离与化学结构

最近,我们研究了云南产的金丝矮陀陀植物中的甾体生物碱。对植物样品的乙醇提取物作了系统分离,从中得到22个甾体生物碱,     

New secoiridoid glycosides from the roots of Picrorhiza scrophulariiflora

Three new secoiridoid glycosides, named picrogentiosides A (1), B (2) and C (3), have been isolated from the underground parts of Picrorhiza Scrophulariiflora, together with the two known compounds plantamajoside (4) and plantainoside D (5). Their structures were established by spectroscopic analyses and comparisons with data from related compounds. A pilot pharmacological study showed that picrogentiosides A (1) and B (2) have an immunomodulatory effect in vitro.     

Phlomisflavosides A and B, new flavonol bisglycosides from Phlomis spinidens

From the aerial parts of Phlomis spinidens, two new flavonol bisglycosides, phlomisflavosides A (1) and B (2), were isolated together with the known compounds, astragalin, isoquercitrin, lamiridoside, phlomoside A, shanzhiside methyl ester, 8-O-acetylshanzhiside methyl ester, phlorigidoside C, rodioloside (=salidroside), forsythoside B, citroside A and lariciresinol-4'-O-beta-D-glucoside. The structures of the new compounds were elucidated based on spectral and chemical evidence.     

Two new triterpenes from the Rhizome of Dryopteris crassirhizoma, and inhibitory activities of its constituents on human immunodeficiency virus-1 protease

Two new hopane type triterpenes, named dryopteric acids A (1) and B (2), were isolated from the Rhizome of Dryopteris crassirhizoma (Aspiadaceae) together with sixteen known compounds (3-18). Of isolated compounds, ursolic acid (15), and dryopteric acid A (1) and B (2) showed potent inhibitory activities against HIV-1 protease with IC50 values of 8.9-44.5 microM. In addition, acetylated compounds 1 and 2 appreciably increased inhibitory activities with their IC50 values of 1.7 and 10.8 microM, respectively.     

1H and 13C NMR assignments of two new indolic enamide diastereomers from a mangrove endophytic fungus Aspergillus sp

Terpeptin A (1) and B (2), two new members of the indolic enamides, along with three known compounds (3-5) were identified from a strain of Aspergillus sp. (w-6), an endophytic fungus associated with Acanthus ilicifolius. The complete (1)H and (13)C NMR assignments for these compounds were carried out using (1)H, (13)C, DEPT, COSY, HMQC, and HMBC NMR experiments. Terpeptin A and B exhibited modest cytotoxicity against A-549 cell line.     

Bengamides revisited: new structures and antitumor studies

The structural chemistry and biological activity of the bengamide class of compounds have been further characterized. Extracts prepared from recollected Jaspis cf. coriacea from five sites in Fiji were pooled. Six new bengamides, M (7b), N (8a), O (8b), P (9a), Q (9b), and R (10), were identified, accompanied by the known bengamides A (1a), B (1b), E (3a), F (3b), Y (5), Z (6), L (7a), G (11a), H (11b), and I (12). The structures of the new compounds were determined from spectroscopic data, and some were additionally confirmed by semisynthesis. Cytotoxicity screening data were obtained from the NCI-DTP 60 cell screen for bengamides A, B, and P. Bengamides A and B were more potent than bengamide P, with average IC(50) values of 0.046, 0.011, and 2.70 FM, respectively. The in vitro antitumor activity against MDA-MB-435 human mammary carcinoma was also determined for natural bengamides A, B, E, F, P, M, O, and Z and for synthetic samples of B and O. The best activity was observed for the natural bengamides A (IC(50) = 1 nM) and O (IC(50) = 0.3 nM).     

Thiersinines A and B: novel antiinsectan indole diterpenoids from a new fungicolous Penicillium species (NRRL 28147)

[structure: see text] Two novel antiinsectan indole diterpenoids, thiersinines A (1) and B (2), along with seven known paxilline-type compounds, were isolated from organic extracts of a new Penicillium species (P. thiersii NRRL 28147). The structures of 1 and 2 were determined by analysis of 2D NMR data. Thiersinines A and B possess a unique spirocyclic subunit that is unprecedented in previously known compounds of this class. Both compounds exhibit potent activity against the fall armyworm (Spodoptera frugiperda).     

Kitungolides A, B, and C, new diterpenes from a soft coral of a new genus

Three novel compounds, designated kitungolides A (1), B (2), and C (3), were isolated from a soft coral of a new genus collected at Kitungamwe, Kenya. The three new compounds are of a unique heterotricyclic skeleton. The structures and relative stereochemistry of the compounds were elucidated by interpretation of MS, COSY, HMQC, HMBC, and NOESY experiments. [structure: see text]     

莽吉柿中几种双苯吡酮和蒽醌类成分的分离与鉴定

对莽吉柿(Pericarpium Garciniae Mangostanae)85%乙醇提取物进一步分离,得到8个双苯吡酮类化合物和1个蒽酮类化合物,经理化性质和NMR及MS谱学数据鉴定分别为α-倒捻子素-3,6-二乙酸酯（α-mangostin-3,6-diyl diacetate,Ⅰ）、1,5,8-三羟基-3-甲氧基-2,4-双-（3-甲基丁-2-烯）双苯吡酮（8-hydroxycudraxanthone G,Ⅱ）、1,3-二羟基-6,7-二甲氧基-2,8-双-（3-甲基丁-2-烯基）双苯吡酮（Cowaxanthone B,Ⅲ）、1,6-二羟基-3,5-二甲氧基-2-（3-甲基丁-2-烯基）双苯吡酮（Cowaxanthone A,Ⅳ）、1,5-二羟基-4-（3-甲基丁-2-烯基）-6′,6′-二甲基吡喃[2′,3′:3,2]双苯吡酮（trapezifolixanthone,Ⅴ）、1,6-二羟基-6′,6′-二甲基吡喃[2′,3′:7,8]-6″,6″-二甲基吡喃[2″,3″:3,2-]双苯吡酮（brasilixanthone B,Ⅵ）、1,3,5-三羟基-2-（3-甲基丁-2-烯）-4-（1,1-二甲基-2-烯丙基）双苯吡酮（Allanxanthone A,Ⅶ）、1,3,8-三羟基-5-甲氧基-2,4-双-（3-甲基丁-2-烯）双苯吡酮(2,4-di-(3-methylbut-2-enyl)-1,3,8-trihydroxy-5-methoxyxanthone,Ⅷ)、1,4,8-三羟基-6-甲基-3-甲氧基-9,10-蒽酮(1,4,8-trihydroxy-6-methyl-3-methoxy- 9,10-anthraquinone, Ⅸ）。 其中化合物Ⅰ、Ⅴ、Ⅵ、Ⅶ、Ⅸ为首次从藤黄属植物中分离得到,化合物Ⅱ、Ⅲ、Ⅳ、Ⅷ为首次从该植物中分离得到。     

Preparations and photophysical properties of fused and nonfused thienyl bridged MM (M = Mo or W) quadruply bonded complexes

A series of metal-metal quadruply bonded compounds [(tBuCO2)3M2]2(mu-TT) where TT = thienothiophenedicarboxylate and M = Mo, 1A, and M = W, 1B and [(tBuCO2)3M2]2(mu-DTT) where DTT = dithienothiophenedicarboxylate and M = Mo, 2A, and M = W, 2B, has been prepared and characterized by elemental analysis, ESI- and MALDI-TOF mass spectrometry and 1H NMR spectroscopy. Their photophysical properties have also been investigated by steady-state absorption as well as transient absorption and emission spectroscopy. The optimized structures and the predicted low energy electronic transitions were obtained by DFT and time-dependent DFT calculations, respectively, on model compounds. These results, in combination with the respective properties of the compounds [(tBuCO2)3M2]2(mu-BTh) (BTh = 2,5'-bithienyldicarboxylate, M = Mo, 3A, and M = W, 3B), allow us to make a comprehensive comparison of the fused (compounds 1A, 1B, 2A, and 2B) and the nonfused thienyl (compounds 3A and 3B) dicarboxylate bridged compounds of molybdenum and tungsten. The electrochemical studies show singly oxidized radical cations that are valence trapped on the EPR time-scale and are classified as Class 1 (M = Mo) or Class 2 (M = W) on the Robin and Day scale for mixed valence compounds. The new compounds exhibit intense metal to bridge ligand charge transfer absorption bands in the far visible and near IR (NIR) region. Both molybdenum and tungsten complexes show dual emission, but for molybdenum, the phosphorescence is dominant while for tungsten the emission is primarily fluorescence. Femtosecond transient absorption spectroscopy shows that the relaxation dynamics of the S1 states which have lifetimes of approximately 10 ps is dominated by intersystem crossing (ISC), leading to T1 states that in turn possess long lifetimes, approximately 70 micros (M = Mo) or 3 micros (M = W). These properties are contrasted with the photophysical properties of conjugated organic systems incorporating metal ions of the later transition elements.     

Constituents from Leaves of Scolopia chinensis

Two new phenolic glycosides, scolochinenosides A and B ( 1 and 2 ), and a new flavonoid glycoside, scoloside A ( 3 ), were isolated from the leaves of Scolopia chinensis (Lour .) Clos , together with eight known compounds. The structures of the new compounds were established on the basis of chemical and spectroscopic evidences.     

5-Alkylpyrrole-2-carboxaldehyde derivatives from the Chinese sponge Mycale lissochela and their PTP1B inhibitory activities

Two new 5-alkylpyrrole-2-carboxaldehyde derivatives,mycalenitrile-15(1) and mycalenitrile-16(2),along with five known related ones(3-7),were isolated from the South China Sea sponge Mycale lissochela.The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR data with those reported in the literature.In bioassay,compounds 1 and 7 exhibited significant PTPIB(Protein-tyrosine phosphatase 1B,a recognized target for diabetes and obesity) inhibitory activities with IC_(50) values of 8.6 and 3.1 μmoI/L,respectively.A preliminary SAR analysis of the isolated compounds with their PTP1 B inhibitory effects was described.     

Tautomeric behavior of 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines between the hydrazone imine and diazenyl enamine forms in acidic media. Solvent and substituent effects

The 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines 1a-h and 2a-e showed tautomeric equilibria between the hydrazone imine A and diazenyl enamine B forms in a series of mixed trifluoroacetic acid/dimethyl sulfoxide media. The substituent and solvent effects on the tautomer ratios of A to B in a series of mixed media were studied for compounds 1a-h and 2a-e by the nmr spectroscopy. In compounds 1a-h and 2a-e , the ratios of the tautomer B gradually increased with elevation of acid concentration, and the tautomer B exclusively existed in trifluoroacetic acid media. The various acid concentrations (C v/v%, C' mol/1) giving the 1:1 tautomer ratios [C(A:B = 1:1), C'(A:B = 1:1)] were obtained from all compounds (Figures 1–13), and the linear correlation of the Hammett σ_p values with the log C'(A:B = 1:1) values were observed for compounds 1a-h. The larger Hammett σ_p values brought about the larger acid concentrations C(A:B = 1:1) in compounds 1a-h and 2a-e , indicating that the higher acid concentration was required for the stabilization of tautomer B possessing the electron-withdrawing p-substituents R¹, which weakened the basicity of the azo nitrogen atom. Moreover, the ester group R² of compounds 2a-e was found to decrease the electron density of the azo nitrogen atom, since the acid concentration C(A:B = 1:1) of compound 2c (R¹ = H, R² = COOMe, σ_p = O) was 52%, whose value was larger than that of compound 1b (R¹ = CN, R² = H, σ_p = 0.66) [C(A:B = 1:1) = 42%].