7-羟基异黄酮及其衍生物的合成与选择性雌激素受体结合的构效关系研究

以多酚类化合物和多取代苯乙酸类化合物为原料,用一锅法合成了24个7-羟基异黄酮类化合物;并从一锅法制得的3d,3g经脱除甲基得到两个2'-羟基取代的异黄酮化合物4a和4b.雌激素受体(Estrogen receptors,ERs)的选择性结合活性试验表明:26个化合物(包括4个新化合物3r,3s,3u和3v)中,9个化合物与ERβ相对于ERα的选择性作用强于染料木素(Genistein);发现7,8-二羟基异黄酮类化合物与ERβ相对结合能力高于相应7-羟基异黄酮类化合物;4'取代基对化合物与ERβ结合相对于ERα的选择性影响从大到小为:H>Cl>F>OH;2',3'及5'位取代基降低异黄酮对ERα和ERβ的亲和性.     

二羟基蒽醌磷酰化衍生物的合成及表征

分别以4种不同位取代的二羟基葸醌和亚磷酸二乙酯或亚磷酸二丙酯为原料,通过简化的Atheron-Todd合成法合成了一系列二羟基葸醌的磷酰化衍生物,并通过量化计算对葸醌上不同羟基电荷分布进行了研究,发现β-羟基氧上的电荷密度大于β-羟基氧上的电荷密度.所合成化合物的结构均经IR,MS,1H NMR,31p NMR和元素分析确证,并通过荧光猝灭法初步探讨了部分新化合物的生物活性.     

双席夫碱的合成与光谱

由2-羟基苯甲醛或2-羟基-1-萘甲醛和二胺类化合物合成了一系列双席夫碱,其中包括七个新化合物;N,N-二水杨醛缩-1,4-丁二胺,N,N-二水杨醛缩二(4-氨基苯基)甲烷,N,N-二水杨醛缩-1,5-萘二胺,N,N-二(2-羟基-1-萘甲醛)缩-1,4-丁二胺,N,N-二(2羟基-1-萘甲醛)缩-1.3-苯二胺,N,N-二(2-羟基-1-萘甲醛)缩-1.4-苯二胺和N,N-二(-羟基-1-萘甲醛)缩-二(4-氨基苯基)甲烷。测定了它们的紫外和红外光谱,讨论了分子结构与光谱特性之间的关系。极性溶剂,尤其是质子溶剂,有利于醌式结构的存在,由2-羟基-1-萘甲醛和二胺形成的双席夫碱在醇醌互变异构中的醌式结构比相应的由2-羟基苯甲醛所形成的双席夫碱要多,这与分子中羟基的酸性相关。     

双席夫碱的合成与光谱

由2-羟基苯甲醛或2-羟基-1-萘甲醛和二胺类化合物合成了一系列双席夫碱, 其中包括七个新化合物; N,N-二水杨醛缩-1,4-丁二胺, N,N-二水杨醛缩二(4-氨基苯基)甲烷, N,N-二水杨醛缩-1,5-萘二胺, N,N-二(2-羟基-1-萘甲醛)缩-1,4-丁二胺, N,N-二(2羟基-1-萘甲醛)缩-1.3-苯二胺, N,N-二(2-羟基-1-萘甲醛)缩-1.4-苯二胺和N,N-二(-羟基-1-萘甲醛)缩-二(4-氨基苯基)甲烷。测定了它们的紫外和红外光谱, 讨论了分子结构与光谱特性之间的关系。极性溶剂, 尤其是质子溶剂,有利于醌式结构的存在, 由2-羟基-1-萘甲醛和二胺形成的双席夫碱在醇醌互变异构中的醌式结构比相应的由2-羟基苯甲醛所形成的双席夫碱要多, 这与分子中羟基的酸性相关.     

一些丹参醌类二萜醌在电子轰击下的裂解反应—关于一种不常见的(M-O)碎片离子的观察

本文对从丹参、大紫丹参及小红参等三种植物中分得的八个二萜邻醌类化合物及它们的四个衍生物进行了质谱研究,阐明了它们在电子轰击下的裂解途径;并在一些羟基取代的丹参醌类化合物的质谱中,观察到一种不常见的(M—O)碎片离子。亚稳测量与高分辨质谱结果表明,氧的消除是通过醌基与邻近羟基间的功能团相互作用而引起的。     

蒽醌、甲基紫精、N,N-二乙基苯胺与金丝桃蒽酮素光致电子转移的研究

金丝桃蒽酮素(HYP)是有多个羟基的醌类衍生物。在极性溶剂乙腈中,电子给体N,N-二乙基苯胺和电子受体甲基紫精、蒽醌均能有效猝灭其荧光。说明它既具有酚羟基的给电子性能,又有醌类化合物的受电子性能。HYP与平面构型的蒽醌可能形成基态复合物,以不同的方式与其发生光致相互作用。     

醌类化合物与抗坏血酸反应生成醌自由基负离子的ESR研究

醌类化合物广泛存在于动植物体内,许多抗癌药物含有醌核。醌类可经单电子还原生成相应的的醌自由基负离子,后者可转移单电子给分子氧,产生超氧负离子基,并进一步产生对生物细胞有损伤作用的羟基自由基,这被认为是醌类化合物生物毒性的主要来源之一。抗坏血酸作为重要的生物抗氧化剂,在生物保护过程中具有十分重要的意义,本文首     

α-二芳甲基-β-羰基硫代羧酸酯与肼的环合反应:官能化含5-羟基吡唑基的三芳基甲烷类化合物的合成

本文通过α-二芳甲基-β-羰基硫代羧酸酯与肼的环合反应合成了含5-羟基吡唑基的三芳基甲烷类化合物。研究表明,在乙醇回流条件下,α-二芳甲基-β-羰基硫代羧酸酯与肼能有效进行环合反应,高产率制得5-羟基吡唑基三芳甲烷类化合物。该反应条件温和、产率高、操作简单。     

致癌性卤代醌与有机氢过氧化物不依赖金属分解的分子机制及其潜在生物学意义

卤代醌是一类具有致癌活性的化合物.最近,它们作为氯代消毒副产物在饮用水中被检测到.有机氢过氧化物(ROOH)可通过自由基和酶促反应氧化多不饱和脂肪酸产生.先前的研究表明,ROOH可被过渡金属催化分解产生烷氧自由基,从而启动脂质过氧化或进一步分解生成α,β-不饱和醛.然而,目前还不清楚卤代醌能否不依赖过渡金属离子与ROOH以类似方式生成烷氧自由基.综合采用电子自旋共振-自旋捕获、高分辨液相色谱质谱联用及其他分析方法,结果发现,2,5-二氯-1,4-苯醌(DCBQ)可显著增强典型的有机氢过氧化物叔丁基过氧化氢(t-BuO OH)分解,以不依赖金属离子的方式生成叔丁氧自由基.在以上发现的基础上,我们检测和鉴定出一类新型的以碳为中心的醌酮自由基,其是我们之前推测的以氧为中心的醌氧自由基的自旋异构体.我们进而将研究扩展到更具生理意义的内源性脂质氢过氧化物13-过氧羟基-9,11-十八碳二烯酸(13-HPODE)中,发现DCBQ也可以显著增加13-HPODE的分解,产生脂质烷基自由基和具有基因毒性的4-羟基-2-壬烯醛.其他卤代醌也具有类似作用.研究表明,致癌性卤代醌能通过一类新型的不依赖于金属离子的亲核取代和均裂分解的机制,促进有机氢过氧化物分解并生成具有较强反应活性的烷氧、醌酮和脂质烷基自由基,及具有基因毒性的4-羟基-2-壬烯醛.以上研究结果可部分解释卤代醌及其酚类前驱物为何具有潜在的基因毒性和致癌性.     

烟草中5种糖苷类化合物的液相色谱-质谱联用分析

采用反相高效液相色谱-质谱(HPLC-MS)联用技术分析了烟草提取液中的5种糖苷类化合物.将烟叶烘干、磨碎后用95%乙醇提取,提取液用正己烷-乙醚(体积比1∶1)除去油脂,水层经大孔树脂分离除杂后,进HPLC-MS分析,获得了5种糖苷类化合物的结构信息.通过对相对分子质量及碎片离子结构信息的解析,推测5种糖苷类化合物分别为:α-紫罗兰醇-β-D-葡萄糖苷、3-氧代-α-紫罗兰醇-β-D-葡萄糖苷、4-羟基-α-紫罗兰醇-β-D-葡萄糖苷、3-羟基-β-大马酮-β-D-葡萄糖苷和地黄普内酯-β-D-葡萄糖苷.     

Peculiar features of application of pH gradients formed in borate buffer with a polyhydroxy compound for separation of proteins in a free-flow electrophoretic apparatus

The use of pH gradients in borate buffer with a polyhydroxy compound for separation of proteins in a free-flow electrophoretic apparatus is outlined. The composition of the pH gradients, the free-flow apparatus design and its operation, and the main causes of failures in the protein separation are considered.     

Colorimetric sensing of polyhydroxy compounds by an inclusion complex of boronic acid-modified amylose

A novel sensing method for polyhydroxy compounds has been established based on the stimuli-responsive inclusion complex of boronic acid-modified amylose with iodine. An aqueous solution containing the boronic acid-modified amylose and iodine was coloured bluish purple due to encapsulation of iodine within the helical cavity of amylose. When polyhydroxy compounds were added, the solution gradually lost its colour with increasing concentration of polyhydroxy compounds. This colour change was attributed to the dissociation of iodine from the amylose cavity in response to the polyhydroxy compounds. According to detailed examinations, it was concluded that the origin of the responsiveness is derived from an electrostatic repulsion between anionic boronate groups and iodine.     

Terracinolides A and B, Two Bishomoditerpene Lactones with a Novel Carbon Framework from Euphorbia terracina

A methanolic extract of Euphorbia terracina L. has been shown to contain two peracylated polyhydroxy terpenoid lactones with a novel C(22) carbon framework. These metabolites, which have been named terracinolides A (1) and B (2), are based on the same parent compound, but differ in the nature of one of the acyl residues. This novel skeletal system is formally derived from the jatrophane framework by addition of a two-carbon fragment on C-17 (jatrophane numbering).     

Collisionally activated mass spectra of [M?H] ions of polyhydroxy and hydroxy ether compounds

Collision-induced decomposition/mass-analyzed ion kinetic energy or collisionally activated mass spectra of [M ? H]^? ions of polyhydroxy compounds and other alcohols and ethers are reported. The [M ? H]^? ion of each compound is produced under OH^? negative ion chemical ionization mass spectrometric conditions. Characteristic fragmentations are observed that include production of [M ? H ? 2]^?, [M ? H ? 18]^? and [M ? H ? 32]^? ions. Certain other fragment ions in the collisionally activated mass spectra make it possible to distinguish among structural isomers. In polyhydroxy compounds, fragmentation increases as the number of hydroxyl groups increase, and carbon-carbon bond cleavage becomes favored.     

Copper oxide catalyzed domino process for the synthesis of substituted 2H-pyran-2-ones and polyhydroxy coumarin derivatives

An efficient method for the synthesis of substituted 2H-pyran-2-ones and polyhydroxy coumarin derivatives has been developed via CuO-catalyzed C–C bond formation followed by intramolecular cyclization reaction by reacting electron-deficient alkynes with 1,3-diketones and polyhydroxy benzenes, respectively. The domino reaction proceeded smoothly by using commercially available catalysts under reflux in toluene with very good yield.     

Oxidative deamination of benzylamine by electrogenerated quinonoid systems as mimics of amine oxidoreductases cofactors

The reactions of a new type of quinonoid system with benzylamine have been investigated in methanol in order to mimic the reactions occurring in the course of the enzymatic oxidation of amines by quinone cofactors. Under strictly anaerobic conditions, unstable quinonoid species 1(ox)()-4(ox)() have been selectively electrogenerated using anodic-controlled potential electrolysis. Thus, we have demonstrated that 3,4-quinone 1(ox)() is incapable of deaminating benzylamine, while 3,4-iminoquinone species 3(ox)() and 4(ox)() act as efficient catalysts for the autorecycling oxidation of benzylamine: the reaction efficiency reached 64 turnovers. Additional mechanistic investigations reveal that the oxidation of benzylamine by our quinonoid model cofactors proceeds unambiguously via a transamination mechanism, as suggested for many enzymatic systems.     

13C NMR-spectroscopy of substituted xanthones—III: Computer supported structure elucidation of polyhydroxy xanthones

A procedure for developing ¹³C NMR chemical shift additivity rules for all 136 polyhydroxy xanthones, which is based on the method of multiple linear regression analysis with dummy parameters, is reported. A computer search program is presented, which rapidly identifies unkown polyhydroxy xanthones with the help of these additivity rules. The working mode is described and its selectivity demonstrated by means of examples from literature.     

Heterocycle-based isomeric chromophores with substantially varying NLO properties: a new structure-property correlation study

A number of heterocycle-based aromatic and quinonoid molecular systems have been considered for the theoretical study of their electric response properties. The nonlinear optical (NLO) parameters have been calculated by using the ab initio MO and DFT methods. An approximate scheme for calculating the first hyperpolarizability (beta) and second hyperpolarizability (gamma) in the framework of the sum-over-state (SOS) method have been proposed by exploiting the generalized Thomas-Kuhn sum rule (TK-SR). The NLO properties in the present scheme can be evaluated solely from the ground-state dipole moment (mu) and linear polarizability (alpha) and have been found to correlate fairly with the ab initio calculated values. The approximate scheme can be reasonably used to explain the wider range of variation of higher-order polarizabilities in terms of the above quantities. The position of the N atom in the thiazole ring at the ortho position (versus meta position) to the acceptor increases beta and decreases gamma for aromatic compounds, while the reverse trend is found with quinonoid compounds. In the case of the pyridine ring, the shifting of the N atom toward the acceptor enhances gamma, with insignificant variation of beta predicted for both the aromatic and quinonoid molecules. The negative contribution of the cubic polarizability of the quinonoid species increases linearly with alpha(2)/mean transition energy (Delta E).     

Application of factor analysis to the study of the forms of succinylfluorescein present in buffer solutions in aqueous methanol

The pH-dependent forms adopted by the xanthene dye succinylfluorescein in 1:1 v/v aqueous methanol buffers have been deduced from factor analysis of absorbance data measured at six wavelengths in the visible region, and sixteen pH-values. It is concluded that a protonated species and a doubly-charged anion are the only absorbing species at the two ends of the pH-range studied, 1.40-9.77, and the quinonoid neutral and singly charged anion forms, both with similar absorption properties, are the major components in the pH-range 5-6. A colourless minor compound may also be present at around pH 4. Apparent pK values corresponding to the three ionizations involved are 2.90, 4.60 and 6.80, as determined by potentiometry.     

Hairpin conformation of amphidinols possibly accounting for potent membrane permeabilizing activities

Amphidinols are a unique dinoflagellate metabolite with potent antifungal activity. We examined membrane permeabilizing action by amphidinol analogues with structural variations in polyhydroxy and polyene moieties. Consequently, the polyene and polyhydroxy moieties turned out to play important roles in binding to lipid bilayer membrane and in forming ion-permeable pore/lesion across membrane, respectively. NMR-constrained modeling experiments have revealed for the fist time that amphidinols in membrane generally take a hairpin configuration, which plausibly accounts for their potent antifungal and other membrane permeabilizing activities.