有水条件下路易斯酸B(C6F5)3对醛酮的选择性催化还原

近年路易斯酸B（C₆F₅）₃催化的醛酮还原反应研究表明，路易斯酸B（C₆F₅）₃也可以作为一种"耐水"的催化剂在"有水"条件下进行催化反应.这些研究成果对进一步扩展受限路易斯酸碱对（FLPs）化学在水相中的应用及其发展至关重要.以硅烷作为还原剂，在路易斯酸B（C₆F₅）₃催化下成功对14种不同取代的醛酮在温和条件下实现了高效地还原成醇反应，产率可高达100%.通过核磁共振分析对反应机理进行的研究表明，在有水条件下，底物羰基氧与催化剂硼烷之间存在以水介导的相互作用，即可能存在"R¹R²C=O--H-O（-H）--B（C₆F₅）₃"的三组分络合形式.对不同路易斯碱与水及硼烷所组成的"LB--H-O（-H）--B（C₆F₅）₃"三组分复合物之间对应原子间距进行了比较研究，发现这种以水介导的相互作用对醛酮的羰基不仅具有质子化的活化作用，而且与硼烷的络合作用也更有利于硅烷作为还原剂在有水条件下使用.所报道的以硅烷作为还原剂，B（C₆F₅）₃催化的醛酮直接还原成醇反应，首次实现了FLPs在真正有水条件下的催化反应，并更进一步证明了在以硅烷作为还原剂时，体系中存在的水不仅会参与催化反应并会促使反应的进行.对有水条件下FLPs催化的醛酮还原的选择性及其催化反应机理，以及对其他反应的影响还需要更深入的研究.     

芳香胺盐酸盐/硼烷体系催化的氢胺化/还原反应研究

近年来有关受限路易斯酸碱对（FLPs）化学的研究受到了国内外的广泛关注,但有关芳香胺类FLPs的应用研究却极少涉及.本工作以硅烷作为还原剂,路易斯酸三（五氟苯基）硼（BCF）作为催化剂,用芳香胺盐酸盐代替苯胺,可一步反应实现炔烃与苯胺的催化氢胺化还原反应.研究发现,取代基较多的三乙基硅烷在反应中表现出较高的反应活性,吸电子取代基取代的端基芳炔的转化率也较给电子取代基取代的端基芳炔的转化率高.对催化反应的机理研究表明,胺盐与B（C₆F₅）₃及硅烷反应所生成的硼氢化芳胺盐活性中间体"[Ar₂NH₂]⁺[H-B（C₆F₅）₃]^-"的产生和分解速度决定着中间产物亚胺的生成和还原.     

有机胺盐/硼烷体系与炔烃的硼氢化加成反应机理研究

炔烃的立体选择性硼氢化加成反应是有机合成中重要的反应之一.在硅烷的存在下,有机胺盐酸盐/硼烷体系可与炔烃在温和的反应条件下发生计量的加成反应.该反应不仅可高立体选择性地得到Z-式构型的1,2-硼氢化胺盐加成产物,而且反应产率高,产物易于分离提纯.对有机胺盐酸盐/硼烷体系与炔烃的加成反应机理进行的研究表明,胺盐与B（C₆F₅）₃及硅烷反应所生成的硼氢化胺盐"[R₂NH₂]⁺[H-B（C₆F₅）₃]^-",虽然被认为是受限路易斯酸碱对化学的活性中间体,但其本身并不能直接还原炔烃;炔烃必须首先被催化量的路易斯酸B（C₆F₅）₃活化后才可与[H-B（C₆F₅）₃]-加成.同时,胺盐氯阴离子Cl-与路易斯酸B（C₆F₅）₃之间的弱的相互作用直接决定着产物的立体选择性,[H-B（C₆F₅）₃]^-以反式加成的方式进攻活化后的炔烃最终得到Z-式构型的硼氢化加成产物.     

“受阻路易斯酸碱对”催化的2,3-二取代2H-1,4-苯并噁嗪氢化反应机理研究

在受阻路易斯酸碱对（FLPs）催化的2，3-二取代2H-1，4-苯并噁嗪氢化反应中，3号位取代基不同会导致反应效率极大改变，因此我们选取反应活性具有较大差别的三种底物作为模型化合物对其反应机理进行了研究，建立了氢化反应势能面.发现当B（C₆F₅）₃与2，3-二苯基2H-1，4-苯并噁嗪或2-甲基-3-苯基2H-1，4-苯并噁嗪混合后，会形成FLPs与路易斯酸碱加合物的混合物.而将B（C₆F₅）₃与2，3-二甲基2H-1，4-苯并噁嗪混合后主要形成没有催化活性的路易斯酸碱加合物，因其能量低于FLPs，在催化体系中不容易转化为FLPs，这导致三种模型化合物在FLPs催化的氢化反应中效率不同.进一步的取代基电子效应及位阻效应计算表明：B（C₆F₅）₃与2-甲基-3-取代2H-1，4-苯并噁嗪混合后形成的路易斯酸碱加合物和FLPs化合物之间稳定性差别源于3位取代基空间位阻不同.     

理论研究“受阻路易斯酸碱对”催化的烯醇硅醚氢化反应机理

“受阻路易斯酸碱对”(FLPs)催化的烯醇硅醚氢化反应是一类重要的直接合成醇类化合物的方法, 然而目前其反应机理仍不明确. 基于此, 以乙基取代的全氟苯基硼作为路易斯酸(Et-B(C₆F₅)₂), 三叔丁基膦(t-Bu₃P)作为路易斯碱, 烯醇硅醚化的苯乙酮(Me-TMS)作为底物建立了模型反应, 并使用密度泛函理论系统研究了其催化氢化反应机理. 结果显示: FLPs催化的烯醇硅醚氢化反应从Et-B(C₆F₅)₂和t-Bu₃P形成B-P-FLPs开始, 随后会依次经过H₂裂解, H⁺和H^-转移等过程, 其中H⁺转移为决速步, H^-转移无势垒, B-P-FLPs生成及H⁺转移是吸热反应. 升高温度不利于氢化反应发生, 但是增大压力可促进反应进行. 底物取代基效应会影响H^-转移过程, 可能使反应不发生.     

有机胺盐酸盐/B(C6F5)3催化的酸与炔烃选择性加成反应研究

一直以来寻找直接有效的乙烯基官能化合成方法的研究备受关注. 报道了一种新型的有机胺盐酸盐/B(C₆F₅)₃ (BCF)体系催化炔烃与氢氯酸或羧酸的加成反应方法, 可选择性地在炔烃的C(2)位氯代或羧化. 研究了在有机胺盐酸盐/BCF体系催化下, 不同取代的炔烃与无机酸HCl的氢氯化加成反应. 在2,2,4,4-四甲基哌啶盐酸盐/BCF([TMPH]⁺[Cl-B(C₆F₅)₃]^-)催化下, 等物质的量的炔烃和HCl反应时, 端基芳炔的C(2)位一加成产物的比例可高达90%以上, 而端基烷基炔烃的选择性较芳炔差, 叔丁基乙炔的一加成产物只占到67%. 报道了非金属催化剂路易斯酸BCF催化的炔烃与羧酸CF₃COOH的烯醇酯化反应, 端基芳炔的C(2)位烯醇酯化产率可达95%以上, 而二苯基乙炔及非芳香性端基炔的反应活性较低. 首次实现了非金属催化剂FLPs参与催化的炔烃与酸的选择性氢氯化和烯醇酯化加成反应.     

B(C6 F5)3催化吲哚与苯乙炔的区域选择性加成

使用B（C₆F₅）₃替代稀有金属催化剂,实现了绿色、无毒、温和催化吲哚与苯乙炔的加成反应.对吲哚不同位置带有取代基的底物进行拓展,在室温条件下高产率获得了一系列双吲哚烷烃.对机理的初步探究表明,反应首先从苯乙炔被B（C₆F₅）₃活化开始,而后依次受到两分子吲哚进攻,经马氏加成得到相应产物.根据探究结果,给出了可能的反应机理.     

过渡金属甲基磺酸盐催化醇的四氢吡喃化反应

以过渡金属甲基磺酸盐［Mn(CH₃SO₃)₂·2H₂O, Cu(CH₃SO₃)₂·4H₂O, Co(CH₃SO₃)₂·4H₂O和Zn(CH₃SO₃)₂·4H₂O］为催化剂,在室温条件下催化醇的四氢吡喃化反应,并对反应条件进行了优化。结果表明：当醇用量为30 mmol,醇和3,4-二氢吡喃摩尔比为1.0 ：1.1,甲基磺酸盐用量为1 mmol,二氯甲烷20 mL时,可高效催化醇的四氢吡喃化反应。与路易斯酸催化活性相比,过渡金属甲基磺酸盐催化醇的四氢吡喃化反应效果最好,催化酚的效果较差。用Mn(CH₃SO₃)₂·2H₂O和Cu(CH₃SO₃)₂·4H₂O催化正丁醇的四氢吡喃化反应,重复使用5次,收率分别为89%和92%。     

新型双苯并环己酮芳亚胺镍(Ⅱ)催化降冰片烯与甲基丙烯酸丁酯共聚合

采用自制的新型双苯并环己酮芳亚胺镍催化剂双苯并环己酮-2,6-二甲基苯亚胺镍(Ⅱ)(Ni{C₁₀H₈(O)C[2,6-C₆H₃(CH₃)₂N]CH₃}₂, C1)和双苯并环己酮-2,6-二氯苯亚胺镍(Ⅱ)(Ni{C₁₀H₈(O)C[2,6-C₆H₃Cl₂N]CH₃}₂, C2)与三五氟苯硼[B(C₆F₅)₃]结合, 在一定的反应条件下可高效催化降冰片烯(NB)与甲基丙烯酸正丁酯(n-BMA)的乙烯基加成共聚合. 提出了催化聚合时存在的可能失活机理; 研究了不同单体投料比对催化活性、 产率及产物性能的影响. 根据Kelen-Tüdõs方法分别估算出2种单体在不同催化体系下的竞聚率, 即当催化体系为C1/B(C₆F₅)₃时, 竞聚率r_n-BMA=0.02, r_NB=16.28, r_NB·r_n-BMA=0.32; 当催化体系为C2/B(C₆F₅)₃时, r_n-BMA=0.01, r_NB=64.83, r_NB·r_n-BMA=0.65. 结果表明, 2种单体在2种体系催化下均为无规共聚合.     

B(C6F5)3催化不饱和烃的硅化反应

有机硅化合物由于其独特的性质,在合成化学、药物化学、高分子化学和有机光电材料等领域具有广泛的应用.不饱和化合物的硅化反应是获得有机硅化合物的重要途径之一,因此引起了化学家的关注并取得了令人瞩目的进展.B(C₆F₅)₃作为一类独特的非金属路易斯酸,近年来,其催化不饱和烃的硅化取得了重要的研究进展,详细介绍了不饱和烃的硅化反应及机理研究.     

Enantiomer separation by CEC——Enantiomer separation by packed-capillary electrochromatography

Three chiral compounds were successfully separated in a short time with two enantiomer separation models on packed-capillary electrochromatography (CEC). (i) 75 μm I.D. capillaries were packed with 5 μm β-cyclodextrin (β-CD) chiral stationary phase (CSP). Effects of voltage, pH and concentration of organic modifier on electroosmotic flow (EOF) and chiral separations were investigated systematically. Enantiomers of a neutral compound (benzoin) and a neutral drug (mephenytoin) were separated within a short time with high efficiency. Efficiency of 32 000 theoretical plates per meter and resolution (R_s) of 1.42 were achieved for enantiomers of benzoin using a βCD packed column with 6.2 cm packed length. Efficiency of 45 000 theoretical plates per meter and R_s of 3.40 were obtained for enantiomers of mephenytoin. Especially, the enantiomer separation of mephenytion was performed in just 3.4 min with R_s of 2.60. (ⅱ) 75 μm I.D. capillary was packed with octadecylsilica particles (ODS). Chiral separat     

Regioselectivity of olefin oxidation by iodosobenzene catalyzed by metalloporphyrins : control by the catalyst

The regioselectivity of the oxidation of three monosubstituted olefins, 6-phenoxyhex-1-ene, hex-1-ene and styrene, by iodosobenzene in the presence of various Fe-, Mn- or Cr-tetraaryl-porphyrins, was studied. It was found that, besides epoxides, known products from such systems, allylic alcohols and aldehydes were formed, the latter not being derived from the corresponding epoxides. The relative importance of these reactions greatly depends upon both the metal and porphyrin constituents of the catalyst. More particularly, the competition between epoxidation and allylic hydroxylation can be efficiently controlled by non-bonded interactions between the olefin and porphyrin substituents. No hydroxylation of the aromatic rings and no oxidative dealkylation of the ether function was detected.     

Glycosidase inhibition by macrolide antibiotics elucidated by STD-NMR spectroscopy

A glycosynthase approach was attempted to glycodiversify macrolide antibiotics, using DesR, a family-3 retaining beta-glucosidase involved in the self-resistance mechanism of methymycin production. STD-NMR was used to probe enzyme-substrate interactions. Analysis of competitive STD-NMR experiments between erythromycin A and a chromogenic substrate (pNP-beta-d-glucose) with the hydrolytically inactive nucleophile mutants led us to discover a family of unprecedented glycosidase inhibitors. Analysis of kinetic data with wild-type DesR determined that erythromycin is a competitive inhibitor of the glucosidase (IC50 = 2.8 +/- 0.3 microM and Ki = 2 +/- 0.2 microM) with respect to the hydrolysis of pNP-beta-d-glucose. Comparable inhibitory data was obtained for clarithromycin; however, the inhibitory effect of azithromycin was weak and no significant inhibition was observed with methymycin or d-desosamine. This report documents significant inhibition of glycosidases by macrolide antibiotics and provides insight into the design of novel glycosidase inhibitors based on the macrolactone ring of macrolide antibiotics.     

Membrane solubilization by detergent: resistance conferred by thickness

The commonly held model for membrane dissolution by detergents/surfactants requires lipid transport from the inner to the outer bilayer leaflet ('flip-flop'). Although applicable to many systems, it fails in cases where cross-bilayer transport of membrane components is suppressed. In this paper we investigate the mechanism for surfactant-induced solubilization of polymeric bilayers. To that end, we examine the dissolution of a series of increasingly thick, polymer-based vesicles (polymersomes) by a nonionic surfactant, Triton X-100, using dynamic light scattering. We find that increasing the bilayer thickness imparts better resistance to dissolution, so that the concentration required for solubilization, after a fixed amount of time, increases nearly linearly with membrane thickness. Combining our experimental data with a theoretical model, we show that the dominant mechanism for the surfactant-induced dissolution of polymeric vesicles, where polymer flip-flop across the membrane is suppressed, is the surfactant transport through the bilayer. This mechanism is different both qualitatively and quantitatively from the mechanisms by which surfactants dissolve pure lipid vesicles.     

Antibiotic recognition by binuclear metallo-beta-lactamases revealed by X-ray crystallography

Metallo-beta-lactamases are zinc-dependent enzymes responsible for resistance to beta-lactam antibiotics in a variety of host bacteria, usually Gram-negative species that act as opportunist pathogens. They hydrolyze all classes of beta-lactam antibiotics, including carbapenems, and escape the action of available beta-lactamase inhibitors. Efforts to develop effective inhibitors have been hampered by the lack of structural information regarding how these enzymes recognize and turn over beta-lactam substrates. We report here the crystal structure of the Stenotrophomonas maltophilia L1 enzyme in complex with the hydrolysis product of the 7alpha-methoxyoxacephem, moxalactam. The on-enzyme complex is a 3'-exo-methylene species generated by elimination of the 1-methyltetrazolyl-5-thiolate anion from the 3'-methyl group. Moxalactam binding to L1 involves direct interaction of the two active site zinc ions with the beta-lactam amide and C4 carboxylate, groups that are common to all beta-lactam substrates. The 7beta-[(4-hydroxyphenyl)malonyl]-amino substituent makes limited hydrophobic and hydrogen bonding contacts with the active site groove. The mode of binding provides strong evidence that a water molecule situated between the two metal ions is the most likely nucleophile in the hydrolytic reaction. These data suggest a reaction mechanism for metallo-beta-lactamases in which both metal ions contribute to catalysis by activating the bridging water/hydroxide nucleophile, polarizing the substrate amide bond for attack and stabilizing anionic nitrogen intermediates. The structure illustrates how a binuclear zinc site confers upon metallo-beta-lactamases the ability both to recognize and efficiently hydrolyze a wide variety of beta-lactam substrates.