No abstract

Proteoglycans (PGs) are composed of a protein moiety and a complex glycosaminoglycan (GAG) polysaccharide moiety. GAG chains are responsible for various biological activities. GAG chains are covalently attached to serine residues of the core protein. The first step in PG biosynthesis is xylosylation of certain serine residues of the core protein. A specific linker tetrasaccharide is then assembled and serves as an acceptor for elongation of GAG chains. If the production of endogenous GAG chains is selectively inhibited, one could determine the role of these endogenous molecules in physiological and developmental functions in a spatiotemporal manner. Biosynthesis of PGs is often blocked with the aid of nonspecific agents such as chlorate, a bleaching agent, and brefeldin A, a fungal metabolite, to elucidate the biological roles of GAG chains. Unfortunately, these agents are highly lethal to model organisms. Xylosides are known to prime GAG chains. Therefore, we hypothesized that modified xylose analogs may able to inhibit the biosynthesis of PGs. To test this, we synthesized a library of novel 4-deoxy-4-fluoroxylosides with various aglycones using click chemistry and examined each for its ability to inhibit heparan sulfate and chondroitin sulfate using Chinese hamster ovary cells as a model cellular system.Proteoglycans are composed of a core protein and one or more glycosaminoglycan (GAG) 4 side chains such as chondroitin sulfate (CS) and heparan sulfate (HS). A common linkage tetrasaccharide, GlcA␤(1-3)Gal␤(1-3)Gal␤(1-4)Xyl␤(1-O-Ser), is found between serine residues in core proteins and the GAG polysaccharide side chains (1, 2). Various biological activities of proteoglycans depend critically on interactions of the sulfated GAG side chains with a wide array of proteins, including proteases and protease inhibitors, growth factors and receptors, morphogens, cytokines, and extracellular matrix structural proteins (3, 4). These proteins differentially recognize and bind to specific sulfate groups of GAG chains. GAG chain formation involves the following events: chain initiation by the transfer of xylose residues to certain serine amino acids in the core proteins, assembly of the tetrasaccharide linkage region, elongation by alternate addition of D-glucuronic acid and N-acetyl-D-hexosamine (GlcNAc for HS and GalNAc for CS) units to the linker tetrasaccharide, and finally highly coordinated multiple sulfation/epimerization steps along the GAG chains (5-8).The linkage tetrasaccharide is synthesized by sequential transfer of xylose, galactose, galactose, and glucuronic acid residues from their corresponding sugar nucleotides. The following glycosyltransferases have been shown to be involved in assembly of the linkage region: xylosyltransferase-1/2, galactosyltransferase-1, galactosyltransferase-2, and glucuronyltransferase-1 (see Fig. 1) (9 -14). Furthermore, various chemical modifications such as phosphorylation of xylose at C-2 or sulfation of galactose residues at C-4 and C-6 in the linkage region are predicted t...

Selenapenams, selenacephems, and selenazepines were synthesized using a 2-(trimethylsilyl)ethyl (TSE) protection approach in an extremely simple way. TSE protection for selenium is used for the first time in the synthesis of selenium-containing beta-lactam. Novel intramolecular cycloaddition reaction of selenium with alkynes and allenes is used in the present synthesis.

Selenium-containing heterocyclic compounds have been well recognized, not only because of their remarkable reactivities and chemical properties, but also because of their diverse pharmaceutical applications. In this context, isoselenocyanates have been emerged as a powerful tool for the synthesis of selenium-containing heterocycles, since they are easy to prepare and store and are safe to handle. In this review the recent advances in the development of synthesis methods for selenium-containing heterocycles from isoselenocyanates are presented and discussed.

No abstract

A convenient approach to synthesize novel selenium-beta-lactams, 3-selena-1-dethiacephems and selenazepines, was accomplished via the regioselective iodocyclization reaction. The substituent of allenyl moieties dramatically influenced the regiochemical outcome in the iodocyclization of allene-selenourea derivatives.

In this letter, we report the regioselective iodocyclization reaction of 3-alkynyl-2-(methylthio)quinolines and 3-alkynyl-2-(methylseleno)quinolines for the synthesis of thieno[2,3-b]quinoline and selenopheno[2,3-b]quinoline derivatives. Furthermore, by employing various palladium-catalyzed Sonogashira, Suzuki, and Heck reactions, the structural diversification of the resulting halide derivatives, which can act as the important intermediates for building other valuable compounds, was achieved. All compounds were fully characterized by the FT-IR, mass, H NMR, andC NMR spectral data. Finally, the structure of the thieno[2,3-b]quinoline derivative was confirmed by X-ray crystallography. This methodology provided a novel pathway to access quinoline fused heterocycles via iodocyclization reaction. Furthermore, the reaction process was well elucidated by density functional theory calculations.

No abstract