三种藏药材的化学成分研究

本学位论文报道了西藏产三种藏族传统植物药材的化学成分研究。论文由四章组成，前三章是实验部分，分别报道了尼泊尔黄堇(Corydalis hendersonii Hemsl.)、藏波罗花(Incarvillea younghusbandii Sprague)和全缘叶绿绒蒿(Meconopsis interifolia Franch.)的化学成分研究结果。从这三种青藏高原药用植物中共分离鉴定出33 个化合物，其中1 个是新化合物。第四章概述了罂粟科紫堇属植物的化学和药理研究进展。 第一章为尼泊尔黄堇的化学成分研究。通过正、反相硅胶柱色谱等分离方法从药用植物尼泊尔黄堇的地上部分共分离纯化得到12 个化合物。运用MS、1H-NMR、13C-NMR、DEPT、HMBC、NOESY 等现代波谱学方法将它们的结构鉴定为：刺罂粟碱(1) ， 普托品(2) ， 新那亭(3) ， 斯可任(4) ， tetrahydrothalifendine (5) ，9-methyl-decumbenine C (6)，tetrahydroberberrubine (7)，隐品碱(8)，α-别隐品碱(9)，6,7-methylenedioxy-1(2H)-oxoisoquinolinone (10)，6-丙酮基-5,6 -二氢血根碱(11)和β-谷甾醇(12)。其中化合物6 为新化合物，为首次发现的分子骨架上C-9 位连有甲基的苯肽异喹啉类型生物碱。另外，除化合物1 和2 外，其它9 个生物碱（3～11）均为首次从该种植物中分离得到。同时，我们还对对尼泊尔黄堇中的总生物碱进行了串联质谱分析。 第二章为藏波罗花的化学成分研究。从该药用植物的地上部分共分离得到16个化合物，通过理化常数和波谱数据鉴定为：异佛手柑内酯(1)，6-甲氧基当归素(2)，欧前胡素(3)，花椒毒内酯(4)，珊瑚菜素(5)，水合氧化前胡素(6)，rivulobirin A (7)，齐墩果酸甲酯(8)，咖啡酸甲酯(9)，银桦酸(10)，(D)-boschniakinic acid (11)，对羟基苯甲酸(12) ， tert-O-β-D-glucopyranosyl-(R)-heraclenol (13) ， 5-methoxy-8-O-β-D-glucopyranosyloxypsoralen (14)，前胡苷V(15)和苯乙醇-O-β-D-吡喃葡萄糖-(1→2)-O-β-D-吡喃葡萄糖苷(16)。所有以上化合物均为首次从该种植物中分离得到。另外我们还首次对藏波罗花挥发油的化学成分进行了气相色谱-质谱(GC-MS)联用分析，共鉴定出39 个挥发性成分。 第三章为全缘叶绿绒蒿化学成分的分离鉴定。从传统藏药材全缘叶绿绒蒿地上部分共分离纯化出8 个化合物。通过理化常数和波谱数据将他们的结构分别鉴定为：去甲血根碱(1)，β-谷甾醇(2)，3-羟基-齐墩果烷-12(13)-烯-30-酸(3)，6-丙酮基-5,6-二氢血根碱(4)，木犀草素(5)，胡萝卜苷(6)，quercetin 3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (7)和普托品(8)。其中化合物1，4 和7 为首次从该种药用植物中分离得到。 第四章为综述，总结和归纳了近年来罂粟科紫堇属植物的化学和药理研究进展。 This dissertation consists of four parts. The first, second and third parts report the studies on the chemical constituents from the medicinal plants of Corydalis hendersonii, Incarvillea younghusbandii and Meconopsis interifolia. The forth part reviews the progress of the studies on Corydalis species. The first chapter is about the isolations and identifications of alkalids from the aerial parts of C. hendersonii which is a traditional Tibetan medicine to treat febrifuge, high blood pressure and hepatitis. A new isoquinoline alkaloid, 9-methyl-decumbenine C (6), together with ten known alkaloids, stylopine (1), protopine (2), canadine (3), scoulerine (4), tetrahydrothalifendine (5), tetrahydroberberrubine (7), cryptopine (8), α-allocryptopine (9), 6,7-methylenedioxy-1(2H)-isoquinolinone (10) and 6-acetonyl-5,6-dihydrosanguinarine (11), and β-sitosterol (12) were isolated. Their structures were elucidated by spectroscopic methods. Furthermore, the total alkaloids were analyzed by ESI-MSn. The second chapter is about the isolations and identifications of chemical constituents from the aerial parts of I. younghusbandii. Sixteen compounds were isolated and purified by normal and reversed phase silica gel column chromatography. By spectral analysis, there structures were identified as isobergapten (1), sphondin (2), imperatorin (3), xanthotoxin (4), phellopterin (5), heraclenol (6), rivulobirin A (7), methyl oleanolate (8), methyl caffeate (9), grevillic acid (10), (D)-boschniakinic acid (11), 4-hydroxybenzoic acid (12), tert-O-β-D-glucopyranosyl-(R)-heraclenol (13), 5-methoxy-8-O-β-D-glucopyranosyloxypsoralen (14), decuroside Ⅴ(15), and phenylethyl-O-β-Dglucopyranosyl-(1→2)-β-D-glucopyranoside (16). All of these compounds were isolated from this plant for the first time．By the way, the chemical components of the essential oil from I. younghusbandii were analyzed by GC-MS for the first time. The third chapter is about the the isolations and identifications of the chemical constituents of M. interifolia. Eight compounds were isolated and identified as norsanguinarine (1), β-sitosterol (2), 3-hydroxyolean-12(13)-en-30-oic acid (3), 6-acetonyl-5,6-dihydrosanguinarine (4), luteolin (5), daucosterol (6), quercetin 3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (7) and protopine (8). The compounds 1, 4 and 7 were isolated from this herb for the first time. The last chapter is a review of the research progress of the studies on Corydalis species, which includes the chemical constituents in this genus and their pharmacology.

New sphingolipids with a previously unreported 9-Methyl-C-20-sphingosine moiety from a marine algous endophytic fungus Aspergillus niger EN-13

Asperamides A (1) and B (2), a sphingolipid and their corresponding glycosphingolipid possessing a hitherto unreported 9-methyl-C-20-sphingosine moiety, were characterized from the culture extract of Aspergillus niger EN-13, an endophytic fungus isolated from marine brown alga Colpomenia sinuosa. The structures were elucidated by spectroscopic and chemical methods as (2S,2'R,3R,3'E,4E,8E)-N-(2'-hydroxy-3'-hexadecenoyl)-9-methyl-4,8-icosadien-1,3-diol (1) and 1-O-beta-D-glucopyranosyl-(2S,2'R,3R,3'E,4E,8E)-N-(2'-hydroxy-3'-hexadecenoyl)-9-methyl-4,8-icosadien-1,3-diol (2). In the antifungal assay, asperamide A (1) displayed moderate activity against Candida albicans.

Chiral Synthons from Monoterpenes.1 Stereoselective Syntheses of (-)5S, 6S, 9R-6-Isopropyl-9-Methyl-2-Oxaspiro[4.4]Nonan-3-One and (-) 3aR, 6R, 7aR-3a-Methyl-6-Isopropenylhexahydrobenzofuran-2-One

Highly stereoselective syntheses of two C-12 chiral synthons 3 and 9, mentioned in the title, starting from the monoterpenes R-1 imonene and R-carvone, using radical cyc 1 sation as key reaction, are described.

Low-lying excited states and nonradiative processes of 9-methyl-2-aminopurine

he UV spectrum of the adenine analogue 9-methyl-2-aminopurine (9M-2AP) is investigated with one- and two-color resonant two-photon ionization spectroscopy at 0.3 and 0.05 cm−1 resolution in a supersonic jet. The electronic origin at 32 252 cm−1 exhibits methyl torsional subbands that originate from the 0A′′1 (l = 0) and 1E ″ (l = ±1) torsional levels. These and further torsional bands that appear up to 000+230 cm−1 allow to fit the threefold (V 3) barriers of the torsional potentials as ∣∣V′′3∣∣=50 cm−1 in the S 0 and ∣∣V′3∣∣=126 cm−1 in the S 1 state. Using the B3LYP density functional and correlated approximate second-order coupled cluster CC2 methods, the methyl orientation is calculated to be symmetric relative to the 2AP plane in both states, with barriers of V′′3=20 cm−1 and V′3=115 cm−1. The 000 rotational band contour is 75% in-plane (a/b) polarized, characteristic for a dominantly long-axis 1ππ* excitation. The residual 25% c-axis polarization may indicate coupling of the 1ππ* to the close-lying 1 nπ* state, calculated at 4.00 and 4.01 eV with the CC2 method. However, the CC2 calculated 1 nπ oscillator strength is only 6% of that of the 1ππ* transition. The 1ππ* vibronic spectrum is very complex, showing about 40 bands within the lowest 500 cm−1. The methyl torsion and the low-frequency out-of-plane ν′1 and ν′2 vibrations are strongly coupled in the 1ππ* state. This gives rise to many torsion-vibration combination bands built on out-of-plane fundamentals, which are without precedence in the 1ππ* spectrum of 9H-2-aminopurine [S. Lobsiger, R. K. Sinha, M. Trachsel, and S. Leutwyler, J. Chem. Phys.134, 114307 (2011)]. From the Lorentzian broadening needed to fit the 000 contour of 9M-2AP, the 1ππ* lifetime is τ ⩾ 120 ps, reflecting a rapid nonradiative transition.

Addition of hydrogen cyanide to 9-methyl- Δ4-octalone-3 and 9β-methyl-8β-hydroxy- Δ4-octalone-3

Addition of hydrogen cyanide to 9-methyl-Δ4-octalone-3 (IIb), as a model, yielded both cis- and trans-ketonitriles the configurations of which are assigned on the basis of IR spectra of the hydrolysed products. Similar addition of hydrogen cyanide to 9β-methyl-8β-hydroxy-Δ4-octalone-3 (IIc) gave the corresponding cis- and trans-hydroxy-keto-nitriles, configurations of which were proved by their conversion into cis- and trans-keto-nitriles obtained in the model study. In contrast to the model experiment where the trans-product predominated, the cis-isomer was the major product of addition to IIc.

High resolution methyl selective C-13-NMR of proteins in solution and solid state

New C-13-detected NMR experiments have been devised for molecules in solution and solid state, which provide chemical shift correlations of methyl groups with high resolution, selectivity and sensitivity. The experiments achieve selective methyl detection by exploiting the one bond J-coupling between the C-13-methyl nucleus and its directly attached C-13 spin in a molecule. In proteins such correlations edit the C-13-resonances of different methyl containing residues into distinct spectral regions yielding a high resolution spectrum. This has a range of applications as exemplified for different systems such as large proteins, intrinsically disordered polypeptides and proteins with a paramagnetic centre.

Study of (9)Be+(12)C elastic scattering at energies near the Coulomb barrier

In this work, angular distribution measurements for the elastic channel were performed for the (9)Be + (12)C reaction at the energies E(Lab) = 13.0, 14.5, 17.3, 19.0 and 21.0 MeV, near the Coulomb barrier. The data have been analyzed in the framework of the double folding Sao Paulo potential. The experimental elastic scattering angular distributions were well described by the optical potential at forward angles for all measured energies. However, for the three highest energies, an enhancement was observed for intermediate and backward angles. This can be explained by the elastic transfer mechanism. (C) 2011 Elsevier B.V. All rights reserved.

Versão Portuguesa da Escala de Perceção da Criança sobre os Conflitos Interparentais – Versão para crianças dos 7 aos 9 anos (EPCCI-C)

As perceções da criança acerca dos conflitos interparentais constituem um importante fator mediador do impacto que estes têm no seu desenvolvimento, pelo que se torna crucial uma adequada avaliação. Neste artigo apresentamos a versão portuguesa da Escala de Perceção da Criança dos Conflitos Interparentais (EPCCI-C), cujo original designado por Children’s Perception of Interparental Conflict Scale for Young Children (CPIC-Y) foi desenvolvido por Grych em 2000. Esta escala de autorrelato tem como objetivo avaliar as perceções produzidas pelas crianças entre os sete e os nove anos de idade acerca dos conflitos entre os pais, tais como as características dos incidentes, a perceção de ameaça, de culpa e a representação sobre a relação pais-criança. Esta versão foi testada em contexto escolar com uma amostra de crianças do 1º ciclo de ensino básico e revelou boas qualidades psicométricas. Estas propriedades e outros elementos caracterizadores do instrumento são discutidos neste artigo.

1H and 13C NMR spectral studies of C-2 substituted isomeric exo- and endo-5-methyl-bicyclo[3.2.1]octane-6,8-diones

A detailed analysis of the 1H and 13C NMR spectra of C-2 aryl and alkyl/desalkyl substituted isomeric exo- and endo-5-methylbicyclo[3.2.1]octane-6,8-diones is presented. The chemical shift of the C-5 angular methyl, the C-2 alkyl/olefinic (C-10)/C-2 methine protons, the aromatic proton shieldings and the characteristic AMX and ABX spectral pattern of the ketomethylene and bridgehead protons were found to be sensitive to the phenyl ring orientation (anisotropy). These distinctive features could be used for configurational distinction for this class of compounds. With increasing ortho-methoxy substitution on the phenyl ring, considerable deshilelding of the bridgehead proton was observed (ca. 0.6 ppm). Absence of the C-2 alkyl group in the desalkyl isomers resulted in substantial changes in the chemical shifts of different protons. A study of the NMR spectra of the corresponding bicyclic compounds with C-2 methoxy/hydroxy substitution instead of the aryl group revealed that the anisotropy of the phenyl ring and the electronegative oxygen substituents have opposite effects. The 13C NMR spectral assignment of each carbon resonance of C-2 aryl and alkyl/desalkyl substituted isomeric exo- and endo-5-methylbicyclo[3.2.1]octane-6,8-diones and the corresponding C-2 methoxy/hydroxy/chloro and methyl bicyclic compounds are reported. Additional ortho-methoxy substitution on the phenyl ring was found to produce considerable high field shifts of the C-10 and C-1 carbon resonances. A high-field shift was observed for the C-6 and C-8 carbonyl carbons, presumably due to 1,3-dicarbonyl interactions. The chemical shifts of C-1 aromatic, C-10 alkyl and C-2 carbons, which are sensitive to exo/endo isomerism, could be utilized in differentiating a pair of isomers.

Synthetic Triterpenoid Cyano Enone of Methyl Boswellate Activates Intrinsic, Extrinsic, and Endoplasmic Reticulum Stress Cell Death Pathways in Tumor Cell Lines

We explored the effect of a novel synthetic triterpenoid compound cyano enone of methyl boswellates (CEMB) on various prostate cancer and glioma cancer cell lines. CEMB displayed concentration-dependent cytotoxic activity with submicromolar lethal dose 50% (LD(50)) values in 10 of 10 tumor cell lines tested. CEMB-induced cytotoxicity is accompanied by activation of downstream effector caspases (caspases 3 and 7) and by upstream initiator caspases involved in both the extrinsic (caspase 8) and intrinsic (caspase 9) apoptotic pathways. By using short interfering RNAs (siRNA), we show evidence that knockdown of caspase 8, DR4, Apaf-1, and Bid impairs CEMB-induced cell death. Similar to other proapoptotic synthetic triterpenoid compounds, CEMB-induced apoptosis involved endoplasmic reticulum stress, as shown by partial rescue of tumor cells by siRNA-mediated knockdown of expression of genes involved in the unfolded protein response such as IRE1 alpha, PERK, and ATF6. Altogether, our results suggest that CEMB stimulates several apoptotic pathways in cancer cells, suggesting that this compound should be evaluated further as a potential agent for cancer therapy. Mol Cancer Ther; 10(9); 1635-43. (C)2011 AACR.

Low temperature crystal structures of two rhodanine derivatives, 3-amino rhodanine and 3-methyl rhodanine: geometry of the rhodanine ring

Rhodanines (2-thio-4-oxothiazolidines) are synthetic small molecular weight organic molecules with diverse applications in biochemistry, medicinal chemistry, photochemistry, coordination chemistry and industry. The X-ray crystal structure determination of two rhodanine derivatives, namely (I), 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine], C3H4N2OS2, and (II) 3-methylrhodanine [3-methyl-2-thio-4-oxothiazolidine], C4H5NOS2, have been conducted at 100 K. I crystallizes in the monoclinic space group P2(1)/n with unit cell parameters a = 9.662(2), b = 9.234(2), c = 13.384(2) angstrom, beta = 105.425(3)degrees, V = 1151.1(3) angstrom(3), Z = 8 (2 independent molecules per asymmetric unit), density (calculated) = 1.710 mg/m(3), absorption coefficient = 0.815 mm(-1). II crystallizes in the orthorhombic space group Iba2 with unit cell a = 20.117(4), b = 23.449(5), c = 7.852(2) angstrom, V = 3703.9(12) angstrom(3), Z = 24 (three independent molecules per asymmetric unit), density (calculated) = 1.584 mg/m(3), absorption coefficient 0.755 mm(-1). For I in the final refinement cycle the data/restraints/parameter ratios were 2639/0/161, goodness-of-fit on F-2 = 0.934, final R indices [I > 2sigma(I)] were R1 = 0.0299, wR2 = 0.0545 and R indices (all data) R1 = 0.0399, wR2 = 0.0568. The largest difference peak and hole were 0.402 and -0.259 e angstrom(-3). For II in the final refinement cycle the data/restraints/parameter ratios were 3372/1/221, goodness-of-fit on F(2) = 0.950, final R indices [I > 2sigma(I)] were R1 = 0.0407, wR2 = 0.1048 and R indices (all data) R1 = 0.0450, wR2 = 0.1088. The absolute structure parameter = 0.19(9) and largest difference peak and hole 0.934 and -0.301 e angstrom(-3). Details of the geometry of the five molecules (two for I and three for II) and the crystal structures are fully discussed. Corresponding features of the molecular geometry are highly consistent and firmly establish the geometry of the rhodanine