环糊精衍生物在液相有机合成中的应用

综述了环糊精(包括α-环糊精、β-环糊精和y-环糊精)衍生物在液相有机合成中的应用,主要包括其作为人工合成酶、超分子光学手性源、亲偶极体和微通道反应器在氧化、水解、还原、光催化异构化、1,3-偶极环加成等反应中的应用.其中环糊精衍生物作为人工合成酶应用最广,该催化剂中起催化作用的为环糊精衍生物的修饰基团.与环糊精母体相比,修饰基团的引入增加了环糊精分子中官能团的种类和数量,拓展了环糊精在液相有机合成中的应用,并提高了催化反应的催化活性和选择性.     

氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应

在不对称 Michael加成反应中,有机小分子如伯胺、吡咯烷类衍生物、(硫)脲类、手性方酰胺、联萘类、奎宁类、手性膦、离子液体和肽类等是目前使用的主要催化剂,如果能避免或少量使用有机溶剂,则更符合“绿色化学”的环境友好发展方向.β-环糊精的内腔疏水,而外部亲水,可以类似酶分子结合有机反应物,在水相体系进行催化反应.当β-环糊精分子上连接催化部位或结合部位时,能产生更优异的包结底物和诱导对映选择性的能力.目前基于β-环糊精衍生物构筑人工类酶催化剂用于不对称 Michael加成反应的报道较少.本文通过亲核取代反应将氨基类有机小分子与单(6-O-p-甲苯磺酰基)-β-环糊精结合,得到9个氨基修饰β-环糊精衍生物CD-1–CD-9(收率在24.2%–64.9%,分子结构通过1H NMR,13C NMR和 ESI-MS表征确认),并用于室温水相体系不对称Michael加成的仿生催化反应,以期获得较好的催化反应活性和对映选择性.通过设计不同β-环糊精衍生物的修饰基团结构、改变反应介质pH值和反应底物结构,分析了Michael加成反应体系产物产率和对映选择性的变化,采用2D-1H ROESY NMR、紫外吸收光谱、红外光谱和和量子化学计算,分析了β-环糊精衍生物和反应底物分子的包结状态,探究了反应过程机理.结果显示,在该水相体系中进行的不对称Michael加成反应产物产率和对映体过量值(ee值)受修饰基团结构、反应介质pH值和底物结构影响较大.当反应介质pH值低于6.0时,由于氨基分子被质子化而失去催化活性;当 pH值为7.5时,获得中等水平的对映选择性,通过量子化学在 ONIOM (B3LYP/6-31G(d)：PM3)水平上的优化计算发现,底物分子与β-环糊精衍生物的包结可以出现两种形式：当底物分子的活性部位接近β-环糊精衍生物小口端的修饰基团时,产生分子内催化,诱导反应产生较好的对映选择性;当底物分子的活性部位远离β-环糊精衍生物小口端的修饰基团时,产生分子间催化,几乎没有对映选择性,而这两种情况同时存在.当底物分子以较大的空间位阻与β-环糊精疏水性空腔结合时,产生较好的对映选择性,邻位取代的2-硝基-β-硝基苯乙烯比对位取代的4-硝基-β-硝基苯乙烯 ee值更高,通过量子化学优化计算证实空间位阻效应.应用2-金刚烷酮与β-环糊精衍生物空腔形成竞争性的包结反应实验,产物产率和ee值都下降,说明β-环糊精衍生物的疏水性空腔是产生不对称诱导和催化活性不可或缺的部分,底物分子与β-环糊精衍生物的包结过程通过2D-1H ROESY NMR和紫外吸收图谱获得确认.其中L-2-氨甲基吡咯烷修饰β-环糊精 CD-1表现出较好的反应对映选择性,在溶剂(pH =7.5,0.5 mol/L CH3COONa-HCl)2 mL,环己酮2 mmol,2-硝基-β-硝基苯乙烯0.2 mmol,CD-1用量0.04 mmol,25°C反应96.0 h的条件下,环己酮与2-硝基-β-硝基苯乙烯 Michael加成产物的 ee值达71%,产率为47%.该反应过程在β-环糊精衍生物的疏水性空腔内进行,修饰基团L-2-氨甲基吡咯烷与环己酮形成烯胺的催化反应.     

氨基修饰β-环糊精衍生物水相仿生催化不对称Michael加成反应（英文）

在不对称Michael加成反应中,有机小分子如伯胺、吡咯烷类衍生物、(硫)脲类、手性方酰胺、联萘类、奎宁类、手性膦、离子液体和肽类等是目前使用的主要催化剂,如果能避免或少量使用有机溶剂,则更符合"绿色化学"的环境友好发展方向.β-环糊精的内腔疏水,而外部亲水,可以类似酶分子结合有机反应物,在水相体系进行催化反应.当β-环糊精分子上连接催化部位或结合部位时,能产生更优异的包结底物和诱导对映选择性的能力.目前基于β-环糊精衍生物构筑人工类酶催化剂用于不对称Michael加成反应的报道较少.本文通过亲核取代反应将氨基类有机小分子与单(6-O-p-甲苯磺酰基)-β-环糊精结合,得到9个氨基修饰β-环糊精衍生物CD-1–CD-9(收率在24.2%–64.9%,分子结构通过~1H NMR,~(13)CNMR和ESI-MS表征确认),并用于室温水相体系不对称Michael加成的仿生催化反应,以期获得较好的催化反应活性和对映选择性.通过设计不同β-环糊精衍生物的修饰基团结构、改变反应介质pH值和反应底物结构,分析了Michael加成反应体系产物产率和对映选择性的变化,采用2D-~1HROESY NMR、紫外吸收光谱、红外光谱和和量子化学计算,分析了β-环糊精衍生物和反应底物分子的包结状态,探究了反应过程机理.结果显示,在该水相体系中进行的不对称Michael加成反应产物产率和对映体过量值(ee值)受修饰基团结构、反应介质pH值和底物结构影响较大.当反应介质pH值低于6.0时,由于氨基分子被质子化而失去催化活性;当pH值为7.5时,获得中等水平的对映选择性,通过量子化学在ONIOM(B3LYP/6-31G(d):PM3)水平上的优化计算发现,底物分子与β-环糊精衍生物的包结可以出现两种形式:当底物分子的活性部位接近β-环糊精衍生物小口端的修饰基团时,产生分子内催化,诱导反应产生较好的对映选择性;当底物分子的活性部位远离β-环糊精衍生物小口端的修饰基团时,产生分子间催化,几乎没有对映选择性,而这两种情况同时存在.当底物分子以较大的空间位阻与β-环糊精疏水性空腔结合时,产生较好的对映选择性,邻位取代的2-硝基-β-硝基苯乙烯比对位取代的4-硝基-β-硝基苯乙烯ee值更高,通过量子化学优化计算证实空间位阻效应.应用2-金刚烷酮与β-环糊精衍生物空腔形成竞争性的包结反应实验,产物产率和ee值都下降,说明β-环糊精衍生物的疏水性空腔是产生不对称诱导和催化活性不可或缺的部分,底物分子与β-环糊精衍生物的包结过程通过2D-~1HROESYNMR和紫外吸收图谱获得确认.其中L-2-氨甲基吡咯烷修饰β-环糊精CD-1表现出较好的反应对映选择性,在溶剂(pH=7.5,0.5mol/LCH_3COONa-HCl)2mL,环己酮2mmol,2-硝基-β-硝基苯乙烯0.2mmol,CD-1用量0.04mmol,25°C反应96.0h的条件下,环己酮与2-硝基-β-硝基苯乙烯Michael加成产物的ee值达71%,产率为47%.该反应过程在β-环糊精衍生物的疏水性空腔内进行,修饰基团L-2-氨甲基吡咯烷与环己酮形成烯胺的催化反应.     

新型β-希夫碱衍生化β-环糊精键合硅胶手性固定相的合成与色谱性能研究

环糊精及其衍生物在手性分离、模拟酶及手性催化剂药物转运等方面都有一定的应用[1～3].设计并合成新型的环糊精衍生物并扩大其应用范围是非常必要的[4,5].近年来,手性希夫碱作为配体已在不对称催化反应中有很好的应用[6].我们将手性希夫碱配体中的刚性CN片断引入到环糊精中制成键合固定相,并通过增加键合固定相与被分离物质间的电荷转移、偶极-偶极及氢键作用,试图改变β-环糊精键合固定相的分离选择性.本文报道了苯亚胺环糊精固定相(BCDs)和异丙亚胺环糊精固定相(YBCDs)的合成方法,探讨了其对DL-氨基酸对映体的分离能力以及流动相的…     

联二萘酚配合物催化的不对称异原子Diels-Alder反应研究进展

光学活性的联二萘酚及其衍生物作为优良的手性配体在不对称催化反应中的研究已经取得重大进展,本文概述了近些年来以联二萘酚及其衍生物为手性配体和各种金属盐形成的配合物作为手性催化剂在不对称催化的异原子Diels-Alder反应中的应用.总结了各种基于联二萘酚及其衍生物的用于异原子Diels-Alder反应的新的催化剂,以及能有效不对称催化该反应的新条件及新方法.     

β-环糊精超分子催化剂用于液相有机合成

详细介绍了β-环糊精超分子作为催化剂应用于液相有机合成, 包括开环、脱保护、保护、氧化、还原、加成、置换等反应的研究进展. 对β-环糊精的催化性能和反应底物选择性能进行分析, 认为β-环糊精与底物的相互作用可有效地催化液相有机化学反应, 提高反应选择性. 提出对β-环糊精进行功能化修饰将促使其在液相有机合成反应中有更大的发展前景.     

Triphos配体在羧酸及其衍生物和CO_2的氢化反应中的应用研究进展

羧酸及其衍生物和二氧化碳中羰基的还原无论在基础研究中还是在工业生产上都是最重要的转化之一.在环境问题日益严峻的今天,以氢气作为还原剂实现这些化合物的还原具有极大的吸引力.由于均相催化反应具有反应条件温和、活性高及催化体系易于调节等优点,发展高效、高选择性的均相催化氢化体系来实现这些羰基化合物的还原成为了研究的热点.近年来,过渡金属与不同类型配体形成的催化体系在羧酸衍生物和二氧化碳的氢化反应中的应用得到了深入的研究,取得了一些重要的进展.其中,过渡金属与1,1,1-三(二苯基膦基甲基)乙烷(triphos)形成的催化体系在多种类型羧酸及其衍生物和二氧化碳的氢化中表现出了独特的反应活性和选择性.本文主要介绍triphos与过渡金属钌、钴和铜形成的催化体系在羧酸及其衍生物和二氧化碳的氢化反应方面取得的进展以及相关反应机理的探讨.     

新型β-希夫碱衍生化β-环糊精键合硅胶手性固定相的合成与色谱性能研究

环糊精及其衍生物在手性分离、模拟酶及手性催化剂药物转运等方面都有一定的应用，设计并合成新型的环糊精衍生物并扩大其应用范围是非常必要的。近年来，手性希夫碱作为配体已在不对称催化反应中有很好的应用，我们将手性希夫碱配体中的刚性C=N片断引入到环糊精中制成键合固定相，     

过渡金属催化的不对称交叉脱氢偶联反应研究进展

C—C键的形成是药物合成过程中重要的研究内容之一.交叉脱氢偶联直接利用不同反应底物中的C—H键在氧化条件下进行交叉偶联反应形成C—C键,反应过程中避免了反应底物的预先官能化,是构建新的碳-碳键简洁、高效的合成路径,原子利用率高、环境友好,具有重大的理论意义和应用价值.综述了目前过渡金属催化的不对称交叉脱氢偶联反应,重点阐述过渡金属与配体在反应的立体选择性中的应用.     

联三吡啶配体及其衍生物合成进展

金属-配体间的配位作用是超分子化学中最重要的相互作用之一, 寡聚吡啶配体可以与许多过渡金属离子配位, 形成具有独特磁、光物理和电化学性质的过渡金属络合物, 因此联三吡啶配体的合成及其过渡金属络合物性能研究引起化学家的广泛关注. 综述了联三吡啶配体及其衍生物的合成方法, 主要包括成环缩合反应、过渡金属催化的偶联反应以及其它方法, 并选取具有代表性的实例对联三吡啶配体的结构和合成方法进行详细地阐述.     

Studies of cyclodextrin-enhanced room-temperature phosphorescence

The enhancement of room-temperature phosphorescence by α-, β- and γ-cyclodextrins in the presence of heavy atoms is described for p-aminobenzoic acid, anthracene and six of its derivatives, dibenzofuran and some other compounds. The sensitivity can be improved by treating the filter paper substrate with the cyclodextrin (preferably β-cyclodextrin) or by mixing the analyte with β-cyclodextrin prior to sample spotting on the substrate.     

Synthesis of a novel poly(oxyethylene)-bridged β-cyclodextrin dimer

A novel supramolecular building block based on cyclodextrin and poly(oxyethylene) is reported, in which the poly(oxyethylene) moiety was selected to be the linker for cyclodextrin in order to enhance the biocompatibility. We report for the first time the synthesis of a bridged β-cyclodextrin dimer based on a condensation reaction by using a simple and efficient procedure, which can be employed for applications in supramolecular chemistry as a nanoscaled building block. It is noteworthy that the dimerization of β-cyclodextrin can increase the binding affinity compared to the β-cyclodextrin derivatives. The chemical structure is biocompatible and the dimer can therefore be considered for drug delivery applications.     

Zinc Complexes of Cyclodextrin‐bearing 8‐Hydroxyquinoline Ligands: A Comparative Study

The mounting evidence supporting the role of metal ions in several diseases has turned metal‐ion chelation therapy into a promising treatment strategy. The design of efficient metal‐binding ligands requires in‐depth knowledge of molecular structure and stability constants of the complexes formed. This paper presents an extensive overview on the stability of zinc(II) and copper(II) complexes of a series of cyclodextrin‐8‐hydroxyquinoline conjugates. In order to explain the differences observed in the stability constants between the metal complexes of the 6‐functionalized and 3‐functionalized cyclodextrin isomers, conformational analysis and DFT simulations were also performed. Molecular simulations allowed us to clarify the binding mode and to explain the differences in the stability constants of the metal complexes of these derivatives.     

Substrate-selective aqueous organometallic catalysis. How small water-soluble organic molecules enhance the supramolecular discrimination

Selective decarboxylation of two alkylallylurethane isomers into alkylallylamines has been performed in a biphasic system by using randomly hydroxypropylated and methylated cyclodextrins as discriminating agents. Surprisingly, the presence of small organic hydrosoluble molecules such as amine or alcohol derivatives appeared to be crucial in the discriminating process. Indeed, it was clearly proved that the presence of such additives enhances greatly the substrate selectivity. For instance, the addition of triethylamine to the reaction medium allows to improve the discriminating power of methylated-β-cyclodextrin by a factor 7. These unexpected results were explained by considering the formation of ternary cyclodextrin/substrate/additive complexes.     

Phosphocontaining Cyclodextrins as a New Class of Supramolecular Structures

Principal peculiarities of the use of phosphocontaining cyclodextrins as a new class of supramolecular structures are discussed. For the first time cyclodextrin perphosphite has been obtained and isolated in an individual state by the treatment of g -cyclodextrin with triazolide neopentylenephosphorous acid. Cyclodextrin perphosphite exhibited an unusual transphosphorylation under reaction with some chlorophosphites. The inclusion of adamantane into the cyclodextrin cavity results in slowing this reaction down. Some water-soluble cyclodextrin derivatives displayed high activity as phase transfer catalysts in biphase catalysis.     

Use of the olefin metathesis reaction for highly efficient β-cyclodextrin modification

A series of novel primary face mono-substituted β-cyclodextrin derivatives have been synthesised using the olefin metathesis reaction. Mono-6-allylamino-6-deoxy-β-cyclodextrin easily synthesised by nucleophilic substitution of mono-6-tosyl-β-cyclodextrin is the key synthon in the preparation of cyclodextrin derivatives mono-functionalised at the primary face by alkyl, aryl or perfluoroalkyl groups using Grubbs catalyst. In the cases of vinylbenzene and 1H,1H,2H-perfluoro-1-octene, the metathesis reactions yield with 95% stereoselectivity of the E-isomer.     

2-氨基-5-烷基-1,3,4-噻二唑修饰环糊精的制备与表征

在N2气保护下, 用单-(6-对甲苯磺酰基)-CD(β-CD-6-OTs)和过量的2-氨基-5-烷基-1,3,4-噻二唑在80 ℃反应2 d, 合成了5种新的2-氨基-5-烷基-1,3,4-噻二唑修饰β-环糊精. 化合物的结构用IR, 1H NMR, 13C NMR, UV, MS和元素分析等方法进行了表征. 由于环糊精的屏蔽效应, 在2-氨基-1,3,4-噻二唑修饰β-环糊精的 1H NMR中, 修饰产物中的噻二唑质子发生了高场位移. 其它的谱图数据同理论值相吻合, 这证明合成与分离方法是可行的. 研究了产物的生物活性, 结果显示部分化合物(2d, 2e)的抗菌活性明显增强.     

Synthesis of per-substituted hydrophilic and hydrophobic ��-cyclodextrin derivatives

The aim of this work was to synthesize new cyclodextrin derivatives from native ??-cyclodextrin by allylation reactions and indium metal in aqueous and organic medium. The resulted products could be used to prepare a new hydrophilic pharmaceutical active ingredient. A hydrophobic derivative can also be prepared by the same method. Indeed, the allylation reactions allow the creation of a stereogenic centers and the introduction of an allyl group lead to development of various functionalization of CD sites. Natural ??-cyclodextrin was treated with allyl bromide and sodium hydride in dimethylformamide (DMF) at room temperature, which resulted in the formation of O-perallylated ??-cyclodextrin A₁ (98%). Through successive reactions of oxidation, reduction and allylation, the latter was converted into per 2, 3, 6-tri-O-(2-hydroxypent-4-enyl) ??-cyclodextrins A₄ (40%). Others derivates of CD type B₃ and C₃ were synthesized by series of reaction to give multifunctionalized cyclodextrins with yield of 25 and 30%, respectively.     

Comparison of Aqueous and 1-Octanol Solubility as well as Liquid–Liquid Distribution of Acyclovir Derivatives and Their Complexes with Hydroxypropyl-β-Cyclodextrin

The aim of the presented work is the comparison of aqueous and 1-octanol solubilities of different acyclovir derivatives and their hydroxypropyl-β-cyclodextrin inclusion complexes. The solubility measurements were carried out at different temperatures over the range 25–45 °C using water, 1-octanol, water saturated with 1-octanol, 1-octanol saturated with water, buffered aqueous solutions (pH = 5.5 and 7.0) and buffered aqueous solutions containing cyclodextrin as solvents. The aqueous solubilities of the compounds are very low but may be enhanced by complexation with hydroxypropyl-β-cyclodextrin, especially if the acyclovir derivatives have aromatic groups which may be included in the cyclodextrin cavity. The values of 1-octanol–water partition coefficients of acyclovir derivatives, obtained using extraction experiments, showed a similar sequence as the solubility results in 1-octanol. Additionally, some molecular mechanics and molecular dynamic calculations were performed to determine optimized structures of acyclovir derivative complexes with β-cyclodextrin treated as a model.     

Synthesis of polyrotaxanes from acetyl-β-cyclodextrin

Polyrotaxanes are intermediary products in the synthesis of topological gels. They are created by inclusion complex formation of hydrophobic linear macromolecules with cyclodextrins or their derivatives. Then, pairs of cyclodextrin molecules with covalently linkage were practically forming the nodes of the semi-flexible polymer network. Such gels are called topological gels and they can absorb huge quantities of water due to the net flexibility allowing the poly(ethylene oxide) chains to slide through the cyclodextrin cavities, without being pulled out altogether. For polyrotaxane formation poly(ethylene oxide) was used like linear macromolecules. There are hydroxyl groups at poly(ethylene oxide) chains, whereby the linking of the voluminous molecules should be made. To avoid the reaction of cyclodextrin OH groups with stoppers, they should be protected by, e.g., acetylation. In this work, the acetylation of the OH groups of β-cyclodextrin was performed by acetic acid anhydride with iodine as the catalyst. The acetylation reaction was assessed by the FTIR and HPLC method. By the HPLC analysis was found that the acetylation was completed in 20 minutes. Inserting of poly(ethylene oxide) with 4000 g/mol molecule mass into acetyl-β-cyclodextrin with 2:1 poly(ethylene oxide) monomer unit to acetyl-β-cyclodextrin ratio was also monitored by FTIR, and it was found that the process was completed in 12 h at the temperature of 10°C. If the process is performed at temperatures above 10°C, or for periods longer than 12 hours, the process of uncontrolled hydrolysis of acetate groups was initiated.