Search

A new synthesis of di- and trisubstituted pyrroles is achieved by treating vinylogous diazoesters and readily available nitriles with a catalytic amount of silver(I) antimony hexafluoride.

Carbohydrate–protein interactions are involved in a multitude of biological recognition processes. Since individual protein–carbohydrate interactions are usually weak, multivalency is often required to achieve biologically relevant binding affinities and selectivities. Among the possible mechanisms responsible for binding enhancement by multivalency, the simultaneous attachment of a multivalent ligand to several binding sites of a multivalent receptor (i.e. chelation) has been proven to have a strong impact. This article summarizes recent examples of chelating lectin ligands of different size. Covered lectins include the Shiga-like toxin, where the shortest distance between binding sites is ca. 9 A, wheat germ agglutinin (WGA) (shortest distance between binding sites 13–14 A), LecA from Pseudomonas aeruginosa (shortest distance 26 A), cholera toxin and heat-labile enterotoxin (shortest distance 31 A), anti-HIV antibody 2G12 (shortest distance 31 A), concanavalin A (ConA) (shortest distance 72 A), RCA120 (shortest distance 100 A), and Erythrina cristagalli (ECL) (shortest distance 100 A). While chelating binding of the discussed ligands is likely, experimental proof, for example by X-ray crystallography, is limited to only a few cases.

This review presents the state of the art of molecular simulation and theory of adsorption, intrusion and freezing in porous silica. Both silica pores of a simple geometry and disordered porous silicas which exhibit morphological and topological disorders are considered. We provide a brief description of the numerical models of porous silicas available in the literature and present the most common molecular simulation and theoretical methods. Adsorption in regular and irregular pores is discussed in the light of classical theories of adsorption and capillary condensation in pores. We also present the different evaporation mechanisms for disordered systems: pore blocking and cavitation. The criticality of fluids confined in pores, which is still the matter of debate, is then discussed. We review theoretical results for intrusion/extrusion and freezing in silica pores and discuss the validity of classical approaches such as the Washburn–Laplace equation and Gibbs–Thomson equation to describe the thermodynamics of intrusion and in-pore freezing. The validity of the most widely used characterization techniques is then discussed. We report some concluding remarks and suggest directions for future work.

Rhodium (II), perfluorobutyrate, Rh 2 (pfb) 4 , is an effective catalyst for the alcoholysis of trialkylsilanes at room temperature. Primary alcohols react with triethylsilane approximately 5 times faster than do secondary alcohols, and tertiary alcohols are virtually inert. Enhanced selectivity is achieved with tert-butyldimethylsilane. Hydrosilylation of olefinic alcohols is relatively unimportant even with terminal alkenes, but Rh 2 (pfb) 4 does promote hydrogenation of 3-phenyl-2-propen-1-ol. Selected diols have been silylated with complete regioselectivity in Rh 2 (pfb) 4 -catalyzed reactions with either triethylsilane or tert-butyldimethylsilane. Methanolysis of (S)-(−)-1-naphthylphenylmethylsilane occurs with nearly complete inversion of configuration at silicon, and spectral analysis of the catalytic reactions suggests a mechanism for silane alcoholysis in which the rhodium (II) catalyst coordinates with the silicon hydride to activate silicon for backside nucleophilic attack by the alcohol

Chiral Rh2L4 (L = 4-substituted-oxazolidinones and methyl 2-pyrrolidone-5-carboxylate) having two nitrogen-rhodium bonds in the cis geometry at each rhodium face are effective catalysts for enantioselective intermolecular cyclopropanation reactions.

Chiral, cage-like C3-symmetrical receptors are prepared in a short, modular synthesis and found to be able to enantioselectivly recognise N-Z-Glu in both titration and solubilisation studies.

Galectins are mammalian carbohydrate-binding proteins that are involved in cell-cell and cell-matrix adhesion, cell migration, and growth regulation with relevance to inflammation and tumor spread. These important functions account for the interest to design suitable low molecular weight inhibitors that match the distinct modes of presentation of the carbohydrate recognition domains of the different galectin subfamilies. Using 3,5-di-(2-aminoethoxy)benzoic acid as the branching unit, wedgelike glycodendrimers with two, four, and eight lactose moieties (G1-G3) were synthesized. They were tested in solid-phase competition assays with lactose maxiclusters and various N-glycan branching profiles (miniclusters) as the matrix and also in cell assays. Prototype galectins-1 and -7, chimera-type galectin-3, a plant (AB)(2) toxin, and a lactose-binding immunoglobulin G fraction from human serum were the carbohydrate-binding targets. Potent inhibition and remarkable cluster effects were seen for the homodimeric galectin-1, especially in combination with biantennary N-glycans as the matrix. Remarkably, for the tetravalent G2 glycodendrimer, the inhibitory potency of each lactose unit reached a maximum value of 1667 relative to free lactose. In haemagglutination experiments as a model for cell adhesion, galectin-3 was markedly sensitive to increased sugar valency and a relative potency per lactose of 150 was reached. The spatial orientation of the carbohydrate recognition domains of the endogenous lectins and the branching pattern of the carbohydrates of the glycoprotein matrices used are both important factors in the design and synthesis of glycodendrimers with galectin-selective properties.

Inspired by the structure of tannic acid, first- to third-generation dendrimers containing two, four, and eight galloyl moieties were synthesized. Stability, antioxidant activity and collagen cross-linking activity of the natural product and its dendrimer analogues were compared. The experimental results indicate that polygalloyl dendrimers might be used as new lead compounds to improve the long-term healing characteristics of burn wounds.

Bacterial adhesion is often a prelude to infection. In many cases, this process is governed by protein-carbohydrate interactions. Intervention at this early stage of infection is a conceptually highly attractive alternative to conventional antibiotics that are increasingly prone to resistance. The lack of high-affinity inhibitors of adhesion has proven to be a hurdle for further exploitation of this concept; however, new developments indicate a positive change. Structure-based design at the monovalent level and also evaluation of glycodendrimers and glycopolymers have yielded structures of high affinity. In addition to the development of inhibitors, topics of this review include available structural information of adhesion proteins, carbohydrate specificities of the various pathogens and their adhesion proteins. Other new developments aimed at affecting bacterial adhesion and the use of the adhesins for bacterial detection are also discussed.

A rapid, efficient and versatile microwave-assisted dibutylstannylene-mediated 3-O-alkylation method for galactosides was established. The alkylation reaction was significantly enhanced by microwave irradiation and allowed the use of an alkylating agent too unstable for incorporation using conventional heating.

New and rigid multivalent lactose molecules were prepared. The structures contain lactose-2-aminothiazoline units at the periphery that were formed from a cyclisation of the thiourea sulphur onto the triple bond of the spacer. The lactosides were evaluated as inhibitors against lectin binding in a solid phase inhibition assay. In this assay the glycoprotein asialofetuin was immobilized onto the surface of microtiter plate wells, mimicking cell surface presentation, while mammalian galectins-1, -3 or -5 were in solution. Between the three galectins, the folding pattern and sequence are closely related but the topology of presentation of the carbohydrate recognition domains differs. Strong multivalency effects were observed for the tetravalent lactoside in the inhibition of galectin-3 binding with enhancements of almost 4300-fold compared to lactose. Remarkable selectivity was obtained in the inhibition since relative potencies of the tetravalent lactoside with the proto type galectins-1 and -5 did not exceed a factor of 143 relative to lactose. The binding of the lactosides to galectin-3 was also studied by fluorescence spectroscopy with all components in solution. These studies showed no multivalency effects in the inherent binding affinities.

α-Amino acids with allenyl, vinyl, and acetylenic side chains can be synthesized using non-enolate based strategies. The ester enolate-Claisen rearrangement applied to propargylic esters of N -protected α-amino acids ie of limited utility since only poor yields of allenic product are obtained with the N-Boc glycine esters, the system which give the most reproducible results. However, α-allenyl-α-amino acids that are fully functionalized on the α-carbon are available through the agency of 4-allenyl-2-phenyloxazolones 4 (obtained from propargyl esters of N-benzoyl protected amino acids via cyclization and Claisen rearrangement) provided that Meerwein's reagent is used to facilitate hydrolysis of the benzamide function in 5 . A variety, of α-substituted glycinates, including those with α-vinyl and α-acetylenic functions, can be prepared using a two-step sequence involving condensation of the cationic glycine synthon 22 with various organomagnesiu reagents, followed by hydrolysis.