Synthetic Methodologies

Abstract

The first description of glycosaminoglycans (GAGs) was by J. Mçller in 1836, who isolated ªchondrinº, a sugar-related substance from cartilage that was later shown to contain a sulfo group by Maerner (1889) and renamed ªchondroitsåureº [1]. It was not until 1935 that Karl Meyer discovered hyaluronic acid, initiating the exploration of GAG biochemistry and the identification of different types of GAGs. The past half-century has resulted in substantial progress in the elucidation of GAG fine structure, biosynthesis, and biological functions.GAGs are unbranched, polydisperse, acidic polysaccharides, often covalently linked to a protein core to form proteoglycans (PGs). GAGs extend from a protein core in a brush-like structure. The core protein size ranges from 10 kDa to >500 kDa, and the number of attached GAG chains varies from 1 to >100 [2]. Except for hyaluronic acid, all GAGs are biosynthesized as PGs. The linkage region is the same in all PGs (except for keratan sulfate) and consists of the tetrasaccharide ± glucuronic acid (GlcAp), galactose (Galp), Galp, and xylose (Xylp) ± linked to the hydroxyl group of serine in the polypeptide core (Fig. 15.1) [3]. PGs occur in the membranes of all animal tissues, intracellularly in certain cells (usually in secretory granules) or extracellularly in the matrix, where they are exported to perform a variety of biological functions.GAG biosynthesis is initiated with the synthesis of the core protein, rich in serineglycine repeats [4], to which the linkage region and GAG are attached. GAGs are characterized (with the exception of keratan sulfate) by a repeating core disaccharide structure comprised of uronic acid and hexosamine residues. The amino group of the hexosamine residue is either N-acetylated or N-sulfonated, the uronic acid being either D-glucuronic acid or L-iduronic acid. Moreover, the repeating disaccharide units are O-sulfonated to varying degrees at the 3-, 4-, or 6-positions of the hexosamine residue and at the 2-position of the uronic acid residues. The most common GAGs are heparin, heparan sulfate (HS), hyaluronic acid (HA), chondroitin sulfate (CS), dermatan sulfate (DS), and keratan sulfate (KS) (Tab. 15.1).

Straightforward Synthesis of Novel 1-(2′-α-O-D-Glucopyranosyl ethyl) 2-Arylbenzimidazoles

“…Participating in such interactions are α-glycoside epitopes, found on bacteria, e.g., Mycoplasma , and on numerous mammalian oligosaccharides, for instance sialyl Lewis X (sLe x ). The synthesis of oligosaccharide ligands as potential inhibitors, however, remains laboriously demanding [ 8 , 9 , 10 ].…”