From cyclopentadiene to isoxazoline-carbocyclic nucleosides: a rapid access to biological molecules through aza-Diels-Alder reactions

A rapid access to carbocyclic nucleosides containing a fused isoxazoline ring is proposed through the Grieco cycloaddition of cyclopentadiene to iminium salts. The prolific elaboration of the isoxazoline cycloadducts allowed preparation of the target aminols through the unmasking of the hydroxymethylene group at the C3 level of the azanorbornene structure. The heterocyclic aminols are readily converted into nucleosides via the linear construction of purine heterocycles.     

Crystal structure prediction of aminols: advantages of a supramolecular synthon approach with experimental structures

The supramolecular synthon approach to crystal structure prediction (CSP) takes into account the complexities inherent in crystallization. The synthon is a kinetically favored unit, and through analysis of commonly occurring synthons in a group of related compounds, kinetic factors are implicitly invoked. The working assumption is that while the experimental structure need not be at the global minimum, it will appear somewhere in a list of computationally generated structures so that it can be suitably identified and ranked upward using synthon information. These ideas are illustrated with a set of aminophenols, or aminols. In the first stage, a training database is created of the 10 isomeric methylaminophenols. The crystal structures of these compounds were determined. The prototypes 2-, 3-, and 4-aminophenols were also included in the training database. Small and large synthons in these 13 crystal structures were then identified. Small synthons are of high topological but low geometrical value and are used in negative screens to eliminate computationally derived structures that are chemically unreasonable. Large synthons are more restrictive geometrically and are used in positive screens ranking upward predicted structures that contain these more well-defined patterns. In the second stage, these screens are applied to CSP of nine new aminols carried out in 14 space groups. In each space group, up to 10 lowest energy structures were analyzed with respect to their synthon content. The results are encouraging, and the predictions were classified as good, unclear, or bad. Two predictions were verified with actual crystal structure determinations.     

Wagner–Meerwein rearrangement of [3.3.1] bicyclic N-Boc aminols: vinyl migration in preference to aryl migration

The Wagner–Meerwein rearrangement of [3.3.1] bicyclic N-Boc aminols was established, featuring the migration of the vinyl group instead of the aromatic ring. The structure of the rearrangement product was deduced through extensive spectroscopic studies and confirmed by the synthetic efforts. The scope of the reaction was examined and reasonably good yields were obtained for substrates with alkyl, allyl or benzyl substituent.     

From cyclopentadiene to isoxazoline-carbocyclic nucleosides: a rapid access to biological molecules through nitrosocarbonyl chemistry

A rapid access to carbocyclic nucleosides containing a fused isoxazoline ring is proposed starting from cyclopentadiene. The route involves an hetero Diels-Alder cycloaddition reaction of nitrosocarbonylbenzene followed by a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N-O tether and elaboration of the heterocyclic aminols into nucleosides via linear construction of purine and pyrimidine heterocycles.     

A novel biomimetic condensation of 2-deoxyribose, aryl amine and acetyl acetone to bicyclic aminols catalyzed by InCl3

2-Deoxyribose, an aryl amine and acetyl acetone undergo smooth cyclocondensation in the presence of 10 mol % of InCl₃ under mild conditions to afford the corresponding sugar-derived bicyclic aminols in good yields with moderate diastereoselectivity. This reaction is reminiscent of the celebrated tropinone synthesis of Robinson. The structures of the products are established by using various NMR experiments and X-ray crystallographic studies.     

Design,Synthesis, and Conformational Analysis of Proposed β‐Turn Mimics from Isoxazoline‐Cyclopentane Aminols

Constrained aminols from oxazanorbornene derivatives have the geometrical features to be used as β‐turn inducers. Four different stereoisomers were prepared and spectroscopically characterized (MD calculations, NMR‐titration and VT‐NMR experiments). Temperature coefficients in DMSO are indicative for the existence of an intramolecular hydrogen bond. Chirooptical properties revealed a β‐turn arrangement of all the synthesized compounds, where, depending on the absolute configuration of the cyclopentane spacer, they can be labeled as left‐ or right‐handed turns.     

Synthesis of novel anthracene derivatives of isoxazolino-carbocyclic nucleoside analogues

The synthesis of isoxazolino-carbocyclic nor-nucleosides incorporating an anthracene moiety was properly tuned through nitrosocarbonyl intermediates chemistry, and a variety of analogues were attained starting from stereodefined heterocyclic aminols through the linear construction of purine heterocyclic rings. The synthesis hinges on the exo selective 1,3-dipolar cycloaddition of the stable anthracenenitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene and simple elaborations of the cycloadducts. A selection of nucleoside derivatives were initially tested for their inhibitory activity against a variety of viruses, including Hepatitis B and C, Human Papilloma virus as well as Influenza viruses of type A and B. Modest anti-viral activities were observed in Hepatitis assays while the activities in the cases of Influenza viruses were almost negligible. Good anti-viral activity was found for compound 11bC with no cellular toxicity at the dose tested in the case of Human Papilloma virus.     

A highly chemoselective Boc protection of amines using sulfonic-acid-functionalized silica as an efficient heterogeneous recyclable catalyst

A facile and versatile method for the chemoselective Boc protection of amines has been developed by a treatment with (Boc)₂O in the presence of sulfonic-acid-functionalized silica as a catalyst. The method is general for the preparation of N-Boc derivatives of aliphatic (acyclic and cyclic), aromatic, and heteroaromatic amines; primary and secondary amines; aminols, amino-esters; and sulfonamides. The catalyst works under heterogeneous conditions and can be recycled.     

Parikh–Doering oxidation–dehydration–Ugi cyclization cascade in the development of lactams from formidoalkanols (3>chain length>7)

De novo incorporation of N-formylated aminols as strategic substrates in legendary Ugi cyclization. Lactamization of N-formido alkanols is accomplished by a novel Parikh–Doering oxidation–dehydration–Ugi cyclization cascade leading to the formation of lactams up to eight carbons (ring size; n=1–4) in moderate yields using formidoaminol, substituted aniline, and aliphatic/aromatic carboxylic acid derivatives as starting materials.     

Synthesis and molecular modeling of novel dihydroxycyclopentane-carbonitrile nor-nucleosides by bromonitrile oxide 1,3-dipolar cycloaddition

The regioisomeric cycloadducts of the bromonitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene were easily prepared and elaborated into a novel class of uracil nor-nucleoside derivatives. In the key-synthetic step represented by the reductive N–O bond cleavage, an unusual double ring opening afforded the aminol intermediates containing a β-hydroxynitrile structure. By adapting known protocols, the aminols entered the linear construction of uracil rings. These novel nucleosides were found structurally similar to a potent antiviral compound, Brivudin, and molecular modeling and docking allowed to select one of the two regioisomeric structures as promising candidate for antiviral tests, due to the nice level of binding with the Thymidine Kinase, the enzyme involved in virus replication.     

Catalytic enantioselective synthesis of macrodiolides and their application in chiral recognition

New types of C₂-symmetric chiral macrodiolides are readily obtained via chiral N,N′-dioxide-scandium(iii) complex-promoted asymmetric tandem Friedel–Crafts alkylation/intermolecular macrolactonization of ortho-quinone methides with C3-substituted indoles. This protocol provides an array of enantioenriched macrodiolides with 16, 18 or 20-membered rings in moderate to good yields with high diastereoselectivities and excellent enantioselectivities through adjusting the length of the tether at the C3 position of indoles. Density functional theory calculations indicate that the formation of macrocycles is more favorable than that of 9-membered-ring lactones in terms of kinetics and thermodynamics. The potential utility of these intriguing chiral macrodiolide molecules is demonstrated in the enantiomeric recognition of aminols and chemical recognition of metal ions.

An asymmetric tandem Friedel–Crafts alkylation/intermolecular macrolactonization of ortho-quinone methides with C3-substituted indoles was achieved by using a chiral N,N′-dioxide-scandium(iii) complex.     

Correspondence between molecular functionality and crystal structures. Supramolecular chemistry of a family of homologated aminophenols

The crystal structures and packing features of a family of 13 aminophenols, or supraminols, are analyzed and correlated. These compounds are divided into three groups: (a) compounds 1-5 with methylene spacers of the general type HO-C6H4-(CH2)n-C6H4-NH2 (n = 1 to 5) and both OH and NH2 in a para position; (b) compounds 1a, 2a, 2b, 2c, and 3a in which one or more of the methylene linkers in 1 to 3 are exchanged with an S-atom; and (c) compounds 2d, 1b, and 6a prepared with considerations of crystal engineering and where the crystal structures may be anticipated on the basis of structures 1-5,1a, 2a, 2b, 2c, and 3a. These 13 aminols can be described in terms of three major supramolecular synthons based on hydrogen bonding between OH and NH2 groups: the tetrameric loop or square motif, the infinite N(H)O chain, and the beta-As sheet. These three synthons are not completely independent of each other but interrelate, with the structures tending toward the more stable beta-As sheet in some cases. Compounds 1-5 show an alternation in melting points, and compounds with n = even exhibit systematically higher melting points compared to those with n = odd. The alternating melting points are reflected in, and explained by, the alternation in the crystal structures. The n = odd structures tend toward the beta-As sheet as n increases and can be considered as a variable series whereas for n = even, the beta-As sheet is invariably formed constituting a fixed series. Substitution of a methylene group by an isosteric S-atom may causes a change in the crystal structure. These observations are rationalized in terms of geometrical and chemical effects of the functional groups. This study shows that even for compounds with complex crystal structures the packing may be reasonably anticipated provided a sufficient number of examples are available.     

He+C60↔(He@C60)的反应势垒研究

The reaction barriers of (He+C60(He＠60)) have been calculated by the quantum-chemical method EHMO/ASED in the following four paths: (1) penetrate through the pentagon on the C60 cage; (2) penetrate through the hexagon on the C60 cage,(3) penetrate through the short bond; (4) penetrate through the long bond. Corresponding to each path, there are two choices: (a) while He penetrate C60 cage, the distances of the C’s which are the most adjacent to He are changed with a planar extension and a concerned window is formed; (b) while He penetrate C60 cage, the distances of the C’s which are the most adjacent to He are changed with a spherical extension and a concerned window is formed. The results are given in Figs. 1-2 and Tables 1-2. It is shown that the reaction through path(4) with choice (a) has the least reaction barrier, being optimum. At that case, a window of 9-membered ring is formed. Because the window extension of C6H6 is more free than that of C60, the barrier of He penetrating through C6H6 will be lower than that of He penetrating through C60.     

Gelatin and the Tyndall Effect: A Colorful and Tasty Demonstration

This demonstration is a safe and nontoxic example of the Tyndall effect that utilizes common, even edible, materials. A glass of gelatin and a laser pointer are used to illustrate the Tyndall effect. Laser light is scattered when it is shone through a colloidal gelatin dispersion. At least two glasses of gelatin are aligned so that students can see scattering through the first glass, then a lower overall intensity of scattered light through the second glass. Variations of the demonstration are presented, such as shining the laser light through a glass of salt water to show the effect as the salt dissolves.     

Electrochemical determination of sulfide and sulfite ions by pneumatoamperometry

Sulfide and sulfite ions in aqueous solution are converted through acidification to hydrogen sulfide and sulfur dioxide, which are purged from solution with nitrogen carrier gas. The volatile species are detected through oxidation in 1 M sulfuric acid at an anodically polarized platinum electrode separated from the gas stream by a gas-permeable polymer membrane. Mixtures of sulfide and sulfite are separated and determined independently through pH control during acidification. Interferences from metal ions, which form sulfide precipitates, and other anions, which form volatile species on acidification, are discussed.     

论化学学习中的能量观建构

能量观是中学化学学习中的核心观念。能量观的建构有利于学生形成核外电子运动的能量思维方式,了解从能量的角度研究物质及其转化的思维方法等。能量观建构的基本策略是:(1)在物质的微粒性认识学习中形成物质的微粒具有热能的观念;(2)在原子结构学习中形成核外电子运动的能量思维方式;(3)在元素及其化合物学习中发展高能量的最外层电子不稳定的认识;(4)在化学变化现象的积累学习中强化物质转化伴随有能量变化的认识;(5)通过化学键概念及其理论学习理解物质转化过程中伴随有能量变化;(6)在影响化学反应速率的条件讨论中深化理解有效碰撞理论;(7)在化学热力学问题研究中进一步理解能量守恒;(8)利用概念图技术帮助化学能量观的建构。     

Two-particle friction in a mesoscopic solvent

The effects of hydrodynamic interactions on the friction tensors for two particles in solution are studied. The particles have linear dimensions on nanometer scales and are either simple spherical particles interacting with the solvent through repulsive Lennard-Jones forces or are composite cluster particles whose atomic components interact with the solvent through repulsive Lennard-Jones forces. The solvent dynamics is modeled at a mesoscopic level through multiparticle collisions that conserve mass, momentum, and energy. The dependence of the two-particle relative friction tensors on the interparticle separation indicates the importance of hydrodynamic interactions for these nanoparticles.     

Marangoni instability and spontaneous non-linear oscillations produced at liquid interfaces by surfactant transfer

The systems producing non-linear spontaneous oscillations of the interfacial tension and electric potential are considered and the available criteria for development of convective instability by the surfactant transfer through a liquid interface are discussed. The non-linear oscillations are observed by the surfactant transfer from a point-like source situated in the bulk of liquid, by the transfer of two ionic solutes through a liquid interface in two opposite directions, and by the transfer of ionic solutes through a liquid membrane. All these systems are governed by more complicated mechanisms than merely arising oscillatory convective instability. The main experimental results obtained for these three systems as well as theoretical models proposed for their explanation are discussed.     

金属的生物甲基化作用和环境输送

讨论了生命体与重金属间的相互关系、重金属生物甲基化作用的环境输送及生物富集，评述了重金属的生态危害么及微生物在其环境输送过程中所起的作用。     

Flow-injection system for simultaneous assay of free and total cholesterol in blood serum by use of immobilized enzymes

The sample is split, so that part passes through an immobilized cholesterol esterase column, before passing through an immobilized cholesterol oxidase column. The other part only passes through the latter column. Separate peaks are obtained for free and total cholesterol. The maximum currents of both peaks are linearly related to the concentration of free and total cholesterol, respectively; 10 samples per hour can be processed with a r.s.d. < 2%.