Palladium-catalyzed carbonylation reactions of aromatic halides in the presence of various nucleophiles have undergone rapid development since the pioneering work of Heck and co-workers in 1974, such that nowadays a plethora of palladium catalysts are available for different carbonylative transformations. The carboxylic acid derivatives, aldehydes, and ketones prepared in this way are important intermediates in the manufacture of dyes, pharmaceuticals, agrochemicals, and other industrial products. In this Review, the recent academic developments in this area and the first industrial processes are summarized.

Palladium-catalyzed carbonylation reactions of aryl halides and related compounds.

This is the report of a DOE-sponsored workshop organized to discuss the status of our understanding of charge-transfer processes on the nanoscale and to identify research and other needs for progress in nanoscience and nanotechnology. The current status of basic electron-transfer research, both theoretical and experimental, is addressed, with emphasis on the distance-dependent measurements, and we have attempted to integrate terminology and notation of solution electron-transfer kinetics with that of conductance analysis. The interface between molecules or nanoparticles and bulk metals is examined, and new research tools that advance description and understanding of the interface are presented. The present state-of-the-art in molecular electronics efforts is summarized along with future research needs. Finally, novel strategies that exploit nanoscale architectures are presented for enhancing the efficiences of energy conversion based on photochemistry, catalysis, and electrocatalysis principles.

Charge Transfer on the Nanoscale: Current Status

Chemokines are critical mediators of cell migration during routine immune surveillance, inflammation, and development. Chemokines bind to G protein-coupled receptors and cause conformational changes that trigger intracellular signaling pathways involved in cell movement and activation. Although chemokines evolved to benefit the host, inappropriate regulation or utilization of these proteins can contribute to or cause many diseases. Specific chemokine receptors provide the portals for HIV to get into cells, and others contribute to inflammatory diseases and cancer. Thus, there is significant interest in developing receptor antagonists. To this end, the structures of ligands coupled with mutagenesis studies have revealed mechanisms for antagonism based on modified proteins. Although little direct structural information is available on the receptors, binding of small molecules to mutant receptors has allowed the identification of key residues involved in the receptor-binding pockets. In this review, we discuss the current knowledge of chemokine:receptor structure and function, and its contribution to drug discovery.

Chemokine: receptor structure, interactions, and antagonism.

Increased understanding of the important roles that oligosaccharides and glycoconjugates play in biological processes has led to a demand for significant amounts of these materials for biological, medicinal, and pharmacological studies. Therefore, tremendous effort has been made to develop new procedures for the synthesis of glycosides, whereby the main focus is often the formation of the glycosidic bonds. Accordingly, quite a few review articles have been published over the past few years on glycoside synthesis; however, most are confined to either a specific type of glycoside or a specific strategy for glycoside synthesis. In this Review, new principles for the formation of glycoside bonds are discussed. Developments, mainly in the last ten years, that have led to significant advances in oligosaccharide and glycoconjugate synthesis have been compiled and are evaluated.

New principles for glycoside-bond formation.

Application of cereals and cereal components in functional foods: a review.

Traditionally, access to structurally defined complex carbohydrates has been very laborious Although recent advancements in solid-phase synthesis have made the construction of complex oligosaccharides less tedious, a high level of technical expertise is still necessary to obtain the desired structures We describe the automated chemical synthesis of several oligosaccharides on a solid-phase synthesizer A branched dodecasaccharide was synthesized through the use of glycosyl phosphate building blocks and an octenediol functionalized resin The target oligosaccharide was readily obtained after cleavage from the solid support Access to certain complex oligosaccharides now has become feasible in a fashion much like the construction of oligopeptides and oligonucleotides

http://science.sciencemag.org/content/sci/291/5508/1523.full.pdf

Automated Solid-Phase Synthesis of Oligosaccharides

A general, modular strategy for the first completely stereoselective synthesis of defined heparin oligosaccharides is described. Six monosaccharide building blocks (four differentially protected glucosamines, one glucuronic and one iduronic acid) were utilized to prepare di- and trisaccharide modules in a fully selective fashion. Installation of the α-glucosamine linkage was controlled by placing a conformational constraint on the uronic acid glycosyl acceptors thereby establishing a new concept for stereochemical control. Combination of disaccharide modules to form trans-uronic acid linkages was completely selective by virtue of C2 participating groups. Coupling reactions between disaccharide modules exhibited sequence dependence. While the union of many glucosamine uronic acid disaccharide modules did not meet any problems, certain sequences proved not accessible. Elaboration of glucosamine uronic acid disaccharide building blocks to trisaccharide modules by addition of either one additional glucosamine or uronic acid allowed for stereoselective access to oligosaccharides as demonstrated on the example of a hexasaccharide resembling the ATIII-binding sequence. Final deprotection and sulfation yielded the fully synthetic heparin oligosaccharides.

Modular Synthesis of Heparin Oligosaccharides

Described is an efficient one-pot synthesis of alpha- and beta-glycosyl phosphate and dithiophosphate triesters from glycals via 1,2-anhydrosugars Glycosyl phosphates function as versatile glycosylating agents for the synthesis of beta-glucosidic, beta-galactosidic, alpha-fucosidic, alpha-mannosidic, beta-glucuronic acid, and beta-glucosamine linkages upon activation with trimethylsilyl trifluoromethanesulfonate (TMSOTf) In addition to serving as efficient donors for O-glycosylations, glycosyl phosphates are effective in the preparation of S-glycosides and C-glycosides Furthermore, the acid-catalyzed coupling of glycosyl phosphates with silylated acceptors is also discussed Glycosyl dithiophosphates are synthesized and are also used as glycosyl donors This alternate method offers compatibility with acceptors containing glycals to form beta-glycosides To minimize protecting group manipulations, orthogonal and regioselective glycosylation strategies with glycosyl phosphates are reported An orthogonal glycosylation method involving the activation of a glycosyl phosphate donor in the presence of a thioglycoside acceptor is described, as is an acceptor-mediated regioselective glycosylation strategy Additionally, a unique glycosylation strategy exploiting the difference in reactivity of alpha- and beta-glycosyl phosphates is disclosed The procedures outlined here provide the basis for the assembly of complex oligosaccharides in solution and by automated solid-phase synthesis with glycosyl phosphate building blocks exclusively or in concert with other donors

Oligosaccharide synthesis with glycosyl phosphate and dithiophosphate triesters as glycosylating Agents

Synthesis of C-aryl and C-alkyl glycosides using glycosyl phosphates.

Publisher Summary This chapter discusses an approach for the development of an automated oligosaccharide synthesizer. To meet the demand for molecular tools, new methods for the rapid production of carbohydrates are needed. Carbohydrates are the most stereochemically challenging class of biopolymers to prepare, and different methods have been developed to address their synthesis. In addition to traditional solution-phase chemical synthesis, three methods—enzymatic methods, orthogonal one-pot chemical methods, and automated solid-phase methods—have become increasingly popular for the construction of oligosaccharides. The chapter develops an automated solid-phase approach for the chemical synthesis of oligosaccharides. In this study, by using an acceptor-bound solid-phase glycosylation strategy in a specially designed instrument, poly α- (1 → 2) mannosides as large as a decasaccharide were synthesized. The use of glycosyl phosphates was demonstrated with the synthesis of a dodecamer phytoalexin elicitor b-glucan. During this investigation, high-resolution magic angle-spinning nuclear magnetic resonance (HR-MAS NMR) analysis was used as an on-resin analytical tool. The method described in the chapter is anticipated to have a significant impact on the field of oligosaccharide synthesis. Although there are still a number of challenges to overcome, the automated construction of glycosidic linkages is expected to allow for the preparation of a diverse set of carbohydrate for pharmaceutical and biochemical evaluation.

Emma R. Palmacci

Papers

Automated Solid-Phase Synthesis of Oligosaccharides

Modular Synthesis of Heparin Oligosaccharides

Oligosaccharide synthesis with glycosyl phosphate and dithiophosphate triesters as glycosylating Agents

Synthesis of C-aryl and C-alkyl glycosides using glycosyl phosphates.

Development of an automated oligosaccharide synthesizer.