2,2—二甲基赤霉素A1甲酯的合成

赤霉素(Gibberellins)是一类重要的具有多种生理活性的植物生长刺激素,在农业、植物生理学、园艺学及医学等方面有广泛的用途。某些2,2-二烷基赤霉素衍生物具有很强的生理活性,如2,2-二甲基赤霉素A_4(1)的生理活性是赤霉酸GA_3(3)的50倍。为了深入探讨这类化合物的生理活性及其构效关系,合成一系列新的2,2-二烷基赤霉素衍生物是一项有意义的工作。Beale M.H等通过微生物法将1转化成为2,2-二甲基赤霉素A_1(2),但收率低,后处理烦琐。有关2的化学合成尚未见报道。 本文以赤霉酸GA_3(3)为原料,通过6步化学反应,成功地合成了2,2-二甲基赤霉素A_1甲酯(9_a)及其差向异构体2,2-二甲基表赤霉素A_1甲酯(9_b)。具体合成路线如下:     

Triterpene glycosides from the sea cucumber Eupentacta fraudatrix. Structure and biological action of cucumariosides A1, A3, A4, A5, A6, A12 and A15, seven new minor non-sulfated tetraosides and unprecedented 25-keto, 27-norholostane aglycone

Seven new minor triterpene glycosides, cucumariosides A1 (1), A3 (2), A4 (3), A5 (4), A6 (5), A12 (6) and A15 (7) have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix. Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS. Glycosides 1-7 belong to the group of cucumariosides A, having linear tetrasaccharide carbohydrate moieties without any sulfate group and possessing 3-O-methyl-D-xylose as a terminal monosaccharide unit. The latter peculiarity is rare in sea cucumber glycosides, but typical for the glycosides from E. fraudatrix. Glycosides 1-7 differ from each other by side chain structures in the aglycone moieties; three of them have unique structural features. The first is the presence of a 25-butoxy-group in the side chain of cucumarioside A3 (2), the second is a 23E,25-diene system in cucumarioside A6 (5) and the third is a 25-keto-27-nor-holostane aglycone in cucumarioside A12 (6); these were never previously found in sea cucumber glycosides. Cytotoxic activity of glycosides 1-7 against mouse spleen lymphocytes and the cells of the ascite form of mouse Ehrlich carcinoma, along with hemolytic activity against mouse erythrocytes and antifungal activity were studied. Glycosides 1 and 5 were the most active in all the tests.     

Synthesis and characterization of A3Na10Sn23 (A = Cs, Rb, K) with a new clathrate-like structure and of the chiral clathrate Rb5Na3Sn25

Four new compounds Cs17.4(1)Na60.6(1)Sn138 (1), Rb19.1(1)Na58.9(1)Sn138 (2), K21.3(1)Na56.7(1)Sn138 (3), and Rb20Na12Sn100 (4) were synthesized by fusion of the corresponding elements. The structures were determined by single-crystal X-ray diffraction. Compounds 1-3 are isostructural and crystallize in a new structure type (rhombohedral, R3m, Z = 1, a = 12.4567(9) A, c = 51.533(3) A for 1; a = 12.465(1) A, c = 51.085(3) A for 2; a = 12.456(2) A, c = 50.559(4) A for 3). The structure contains layers of fused pentagonal dodecahedra of tin that alternate with layers of isolated tin tetrahedra. It is an intergrowth between the structure of clathrate-II (A24Sn136) with the same layers of pentagonal dodecahedra and the Zintl phase ASn with Sn4(4-) tetrahedra. Compound 4 is a new chiral clathrate (cubic, P4(1)32, Z = 1; a = 16.4127(7) A) with stoichiometry that corresponds to an electronically balanced Zintl phase.     

High-resolution laser excitation spectroscopy of the A2E-X2A1 transition of SrCH3

High-resolution laser excitation spectroscopy has been used to record the A (2)E-X (2)A(1) electronic transition of SrCH(3) in a laser ablation/molecular jet source. Transitions arising from the K(')=1<--K(")=0, K(')=0<--K(")=1, and K(')=2<--K(")=1 subbands have been observed and assigned. The data were modeled with (2)E and (2)A(1) symmetric top Hamiltonian matrices in a Hund's case (a) basis, using a least squares fitting program. Rotational and fine structure parameters for the A (2)E state were determined. A comparison of the spin-orbit energy separation in the A (2)E state to other strontium containing free radicals showed that the Jahn-Teller effect is negligible. The spin-rotation constants for the A (2)E state were calculated using the pure precession model and were found to be in good agreement with the experimentally determined parameters. These calculations suggest that the A (2)E state of SrCH(3) is not entirely of p orbital character. The rotational constants were used to estimate the structural parameters of SrCH(3) in the A (2)E state. The strontium-carbon bond length was found to decrease by approximately 0.006 A, and the hydrogen-carbon-hydrogen bond angle opened by approximately 0.8 degrees compared to the X (2)A(1) state, similar to the geometry changes observed for CaCH(3).     

Discovery of Novel Acetaldehyde Dehydrogenase 1A1(ALDH1A1) Inhibitors by Utilizing 3D-QSAR,Molecular Docking and Molecular Dynamics Simulation

Acetaldehyde dehydrogenase 1A1 is a hopeful therapeutic target to ovarian cancer. In this present work, 3D-QSAR, molecular docking and molecular dynamics(MD) simulations were implemented on a series of quinoline-based ALDH1A1 inhibitors to investigate novel acetaldehyde dehydrogenase 1A1 inhibitors as anticancer adjuvant drugs for ovarian cancer. Two reliable CoMFA(Q~2 = 0.583, R~2 = 0.967) and CoMSIA(Q~2 = 0.640, R~2 = 0.977) models of ALDH1A1 inhibitors were established. Novel ALDH1A1 inhibitors were predicted by the 3D-QSAR models. Molecular docking reveals important residues for protein-compound interactions, and the results revealed ALDH1A1 inhibitors had stronger electrostatic interaction and binding affinity with key residues of protein, such as Phe171, Val174 and Cys303. Molecular dynamics simulations further verified the results of molecular docking. The above information provided significant guidance for the design of novel ALDH1A1 inhibitors.     

5-芳基-3-二茂铁基二氢吡唑的合成及晶体结构

吡唑环是许多具有生理活性化合物的关键结构,许多吡唑衍生物都显示了较强的生理活性,如镇静止痛、消炎、杀菌、降血糖以及安眠的活性等~([1-3]),特别是芳基吡唑在医药以及农药方面具有重要的应用~([4,5]).     

Lathyranone A: a diterpenoid possessing an unprecedented skeleton from Euphorbia lathyris

Lathyranone A (1), a novel diterpenoid with a rearrangement skeleton, along with a known diterpenoid, Euphorbia factor L(11) (2), was isolated from the seeds of Euphorbia lathyris. The structure and relative stereochemistry of 1 were elucidated by extensive spectroscopic analysis. A possible biosynthetic pathway for lathyranone A (1) was proposed.     

Haptoglobin subtyping with anti-haptoglobin alpha chain antibodies

Specific antibodies against the human haptoglobin (HP) alpha chain were raised and used for immunoblotting after isoelectric focusing to determine Hp alpha subtypes in a reproducible and simplified manner. By eliminating the staining of the HP beta chain, HP alpha subtypes were visualized more precisely and simply than by previously reported methods. Subtypes of a total of 1211 sera, obtained from two different populations in Japan, were examined by the new method. Four HP alpha subtypes (HP 1S-1S,2FS-1S, 2FS-2FS and 2FS-2SS) and five subtypes combined with a new variant (HP 2FS-1V1, 2V1-1S, 2FS-2V1, 2FS-2V2 and 2FS-2V3) were observed. HP 1V1 belonged to HP alpha 1, and HP 2V1, 2V2 and 2V3 belonged to HP alpha 2, and their alleles were designated HP A*1V1, HP A*2V1, HP A*2V2 and HP A*2V3, respectively. The allele frequencies were calculated to be as follows: HP A*1S, 0.2597; HP A*1V1, 0.0004; HP A*2FS, 0.7333; HP A*2SS, 0.0008; HP A*2V1, 0.0045; HP A*2V2, 0.0008; and HP A*2V3, 0.0004. The allele frequency of HP A*2SS, which is common in the European population, is less frequent than HP A*2V1 in the Japanese population.     

Turrapubesins A and B, first examples of halogenated and maleimide-bearing limonoids in nature from Turraea pubescens

[structure: see text] Two novel tetranortriterpenoids, turrapubesins A (1) and B (2), representing the first examples of halogenated and maleimide-bearing limonoids, were isolated from the twigs and leaves of Turraea pubescens. The structures of 1 and 2 were elucidated by extensive spectroscopic analysis. Their absolute configurations were determined by X-ray crystallography of 1 and by CD analysis of a dihydrogenated derivative of 2. Turrapubesin A (1) exhibited weak cytotoxicity against the P-388 tumor cell line.     

1-甲基-2-喹诺酮类衍生物的合成及其抗肿瘤活性

以喹啉类化合物为原料,经甲基化反应和氧化反应制得中间产物2-喹诺酮类化合物(2a~2c); 2a~2c经硝化反应制得7个硝化-2-喹诺酮类化合物{3a~3g); 3a, 3e~3g经移位取代反应合成了4个1-甲基化-4-氰化-2-喹诺酮类衍生物(4a, 4e~4g),其结构经¹H NMR, ¹³C NMR和HR-MS(EI)确证。采用MTT法评价了化合物对MCF-7, H1299, A549, PC-12, CT-26及HepG-2肿瘤细胞的抗增殖作用。研究结果表明：部分化合物对肿瘤细胞的抑制活性明显高于喹啉系列物,其中1,8-二甲基-3,5,7-三硝基-2-喹诺酮(3e)显著抑制六种肿瘤细胞的增殖,对A549的抑制活性最高,IC₅₀为2.05 μmol·L^-1; 1-甲基-6,8-二硝基-4-氰基-2-喹诺酮(4a)可选择性抑制A549和CT-26肿瘤细胞,IC₅₀分别为9.34 μmol·L^-1和18.43 μmol·L^-1。     

多壁碳纳米管诱导A549细胞氧化应激与去极化线粒体膜电位

以人肺上皮细胞系A549为模型细胞, 探讨多壁碳纳米管的细胞毒性效应及其机制. A549细胞暴露于不同浓度(0~300 μg/mL)的多壁碳纳米管后, 用MTT比色法检测细胞活力和Hoechst 33342染色法观察细胞形态; 用活性氧(ROS)敏感探针2',7'-二氯荧光素二乙酸酯(DCFH-DA)结合流式细胞仪检测细胞内ROS水平; 用荧光探针JC-1结合激光共聚焦显微镜检测细胞线粒体膜电位ΔΨm的变化; 用免疫荧光和蛋白印迹法检测细胞氧化应激敏感蛋白血红素氧合酶-1(HO-1)的表达水平. 结果表明, 多壁碳纳米管可引起A549细胞活性降低、细胞内活性氧ROS过量产生以及谷胱甘肽GSH含量下降, 诱导细胞氧化应激效应; 抗氧化剂N-乙酰半胱氨酸(NAC)抑制多壁碳纳米管诱导的A549细胞内ROS的产生. 多壁碳纳米管处理A549细胞2 h后, 诱发细胞线粒体膜电位下降; 多壁碳纳米管诱导细胞氧化应激的同时伴有适应性应激蛋白HO-1的上调表达. 结果表明, 细胞氧化应激和线粒体膜电位去极化可能是多壁碳纳米管诱导A549细胞毒性效应的重要机制.     

Isolation and structures of antibacterial binaphtho-alpha-pyrones, talaroderxines A and B, from Talaromyces derxii.

New compounds designated talaroderxines A (1) and B (2) were isolated from a new heterothallic ascomycetous fungus, Talaromyces derxii, cultivated on rice. The structures of 1a and 1b were elucidated by means of spectroscopic examination and chemical reactions. Talaroderxines A (1a) and B (1b) are atropisomers of a 6,6'-binaphtho-alpha-pyrone derivative, and have strong antibacterial activity against Bacillus subtilis.     

Palmaenones A and B, two new antimicrobial chlorinated cyclopentenones from discomycete Lachnum palmae

Two new antimicrobial chlorinated cyclopentenones, palmaenones A (1) and B (2) were isolated from the culture broth of discomycete Lachnum palmae (NBRC-106495), and the structures of 1 and 2 were elucidated by spectroscopic data and the stereochemistry of 1 was directly determined by a single-crystal X-ray diffraction analysis. Palmaenones A (1) and B (2) are cyclopentenones containing three chlorines. Compound 1 exhibited potent antimicrobial activity against Micrococcus luteus, Mycobacterium smegmatis, Escherichia coli, Xanthomonas campestris, and Mucor racemosus, while the activities of compound 2 were weaker than 1.     

Isolation and purification of antioxidative isomeric polyphenols from the roots of Parthenocissus laetevirens by counter-current chromatography

Upright counter-current chromatography (CCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:2:1:2, v/v/v/v) was applied to the isolation and purification of polyphenols from the roots of Parthenocissus laetevirens. Two cis-trans isomeric resveratrol dimers - quadrangularin A and parthenocissin A - were obtained from the crude sample in a one-step separation, with purities of 95.4 and 97.6%, respectively, as determined by HPLC. The structures of these two compounds were identified by (1)H NMR and (13)C NMR. Furthermore, their antioxidant activities were determined by beta-carotene bleaching assay. The antioxidant activities of quadrangularin A and parthenocissin A were higher than that of vitamin C in this model.     

CCl2(A^1B1)自由基不同振动态的猝灭动力学

对CCl4/Ar混合气体直流脉冲放电产生CCl2自由基，再分别用波长为550.56nm,541.52nm,532.25nm,524.31nm,523.82nm和523.27nm的激光将电子基态CCl2激励到激发态A^1B1的(0,3,0),(0,4,0),(1,3,0),(0,6,0),(1,4,0),(2,2,0)振动态，激发态CCl2(A^1B1)的不同振动态的时间分辨荧光信号显示该信号呈双指数衰减，测得室温下CCl2(A^1B1)不同振动态被NH3,H2O,CH2Br2,NH(CH3)2,NH(C2H5)2,N(C2H5)3,n-C6H14等分子猝灭的实验结果，用三能级模型分析处理实验数据，获得态分辨速率常数kA和ka值，并对实验结果进行了讨论。     

High-performance anion-exchange chromatographic study of desialylated human alpha 1-acid glycoprotein variants. Development of a fractionation method for the protein slow variants

The three main desialylated variants (F1, S and A) of human alpha 1-acid glycoprotein (AAG), a serum acute-phase reactant, were analysed by high-performance anion-exchange chromatography in order to determine their optimum separation conditions. The analysis consisted of three steps, as follows: (1) A desialylated commercial AAG was separated into one "fast"- and one "slow"-migrating fraction by preparative isoelectrofocusing. The "fast" and "slow" fractions were shown to contain the F1 variant and a mixture of the S and A variants, respectively. (2) The pH titration curves of these two fractions were then measured by strong anion-exchange chromatography with several buffer systems of increasing pH. From the data obtained, it was not possible to select the optimum conditions to separate the "fast" variant F1 from the "slow" variants A and S. However, the S and A variants were shown to ionize very differently. (3) The specific fractionation of the S and A variants was therefore carried out by anion-exchange chromatography under operating conditions based on the data obtained from the study of their pH titration curves. This was performed both with the "slow"-migrating fraction obtained by preparative isoelectrofocusing of commercial AAG and with an AAG (containing only variants S and A) purified from an individual serum on immobilized Cibacron Blue F3G-A. Identification of the fractionated proteins was achieved by analytical isoelectrofocusing.     

Synthesis, tautomeric states and crystal structure of (Z)-ethyl 2-cyano-2-(3H-quinazoline-4-ylidene) acetate and (Z)-ethyl 2-cyano-2-(2-methyl-3H-quinazoline-4-ylidene) acetate

The new compounds (Z)-ethyl 2-cyano-2-(3H- and 2-methyl-3H-quinazoline-4-ylidene) acetate (1 and 2, respectively) were synthesized by multi-step reactions. The structures in a solution have been determined by (1)H-NMR spectroscopy and in the crystal form by X-ray analysis. Molecule 1 crystallized in a primitive monoclinic cell, space group capital ER, P2(1/c). The cell dimensions are a=7.970(6) A, b=7.061(2) A, c=20.537(7) A, beta=97.69(5) degrees , V=1145.3(10) A(3). Molecule 2 crystallized in a triclinic cell, space group P-1, the cell dimensions are a=8.196(5) A, b=8.997(6) A, c=9.435(4) A, alpha=74.22(4) degrees, beta=89.75(4) degrees , gamma=74.07(5) degrees , V=641.9(6) A(3). In both compounds the presence of intra-molecular NH---O=C hydrogen bonding between the nitrogen atom in position 3 of the quinazoline ring and a carbonyl group of the ethyl cyanoacetate residue was proven by quantum-chemical, (1)H-NMR and X-ray methods.     

Niobium-arsenic Zintl phases: A(6)NbAs(5) (A = K,Rb, Cs), K(6)NbTlAs(4), and K(8)NbPbAs(5) with edge-bridged niobium-centered tetrahedra of arsenic, [NbAs(4)M](n-) where M = As,Tl, Pb

The five title compounds were prepared by direct reactions of the corresponding elements at high temperature. Their structures contain isolated anions of tetrahedral NbAs(4) where one of the edges of the tetrahedron is bridged by a third atom. The bridging atom is arsenic in A(6)NbAs(5) (monoclinic, P2(1)/c, Z = 8; with a = 25.774(3) A, b = 9.335(1) A, c = 13.012(1) A, beta = 101.05(1) degrees for A = K; a = 27.629(1) A, b = 9.925(1) A, c = 14.111(1) A, beta = 101.63(1) degrees for A = Rb; and a = 27.405(1) A, b = 9.9447(6) A, c = 13.9964(8) A, beta = 101.210(1) degrees for A = Cs), thallium in K(6)NbTlAs(4) (orthorhombic, Pnma, Z = 4, a = 18.786(1) A, b = 10.4442(4) A, c = 7.715(1) A), and lead in K(8)NbPbAs(5) (monoclinic, C2/c, Z = 8, a = 31.597(9) A, b = 9.353(1) A, c = 13.427(2) A, beta = 95.25(1) degrees ). The lead atom in the latter is bonded to a third arsenic atom as well. Magnetic measurements showed diamagnetic behavior, and therefore, the compounds are electronically balanced, closed-shell type compounds and can be described as transition-metal Zintl phases. The bonding in the anion NbAs(5)(6-) is discussed in detail.     

Theoretical transition probabilities for the A 1Pi-X 1Sigma+ system of AlNC and AlCN isomers based on global potential energy surfaces

Transition probabilities were evaluated for the X (1)Sigma(+)-A (1)Pi system of AlNC and AlCN isomers to analyze photoabsorption and fluorescence spectra. The global potential energy surfaces (PESs) of the X (1)Sigma(+) and A (1)Pi (1 (1)A("),2 (1)A(')) electronic states were determined by the multireference configuration interaction calculations with the Davidson correction. Einstein's B coefficients were computed by quantum vibrational calculations using the three-dimensional PESs of these states and the electronic transition moments for the X-1 (1)A(") and X-2 (1)A(') systems. Einstein's B coefficients obtained for AlNC or AlCN exhibit that the Al-N or Al-C stretching mode is strongly enhanced in the transition. The absorption and fluorescence spectra calculated for the X-1 (1)A(") and X-2 (1)A(') systems are discussed comparing with the observed photoexcitation and fluorescence spectra. The lifetimes for the several vibrational levels of the A (1)Pi state were calculated to be ca. 7 ns for AlNC and 21-24 ns for AlCN from the fluorescence decay rates of the 1 (1)A(")-X and 2 (1)A(')-X emissions.     

Salarins a and B and tulearin a: new cytotoxic sponge-derived macrolides

Three novel nitrogenous macrolides designated salarin A and B (1 and 2) and tulearin A (3) were isolated from the Madagascar Fascaplysinopsis sp. sponge. The structures of the compounds were elucidated by interpretation of MS and 1D and 2D NMR spectra. Both salarins carry an acetylcarbamate moiety, and in addition, 1 contains a triacylamine group and 2 a methoxymethylketone lactam. Tulearin A carries the naturally rare carbamate ester. The compounds were found to be toxic to brine shrimp larvae, and salarin A and tulearin A were also cytotoxic to leukemia cells.