The present article deals with a short review on the recent methodological progress in O-glycoside synthesis. Particular stress is laid on the design of newer classes of glycosyl donor, which allow the selective activation/O-glycoside formation under specific reaction conditions. Based on the anomeric leaving group, glycosyl donors are classified into nine classes, 1) fluoride, 2) thioglycoside, 3) O-acylate, 4) O- and S-carbonate derivatives, 5) phosphate derivatives, 6) trichloroacetimidate, 7) 1-hydroxyl sugar, 8) 4-pentenyl glycoside, 9) glycal, and their selective activation methods are tabulated. Also described are the other approaches based on different principles, e.g., glycosylidene carbene, anomeric O-alkylation, internal cyclization or glycoside synthesis based on physical means;light, electric, thermal, and high pressure. Recent topics in this field are also included, 1) new protecting groups, 2) stereochemical control in manno- and 2-deoxy-sugars, and 3) the armed/disarmed concept.
Cellobiose, N, N'-diacetylchitobiose, laminaribiose, and cyclodextrins were available through enzymic degradation of cellulose, chitin, curdlan, and starch, respectively. Several biologically important glycosyl chains were constructed using above three disaccharides as the building blocks or the starting materials. Through careful acetolysis after thorough pre-acetylation, cyclodextrins underwent the specific cleavage of only one glycosidic bond, giving the corresponding acyclic oligosaccharide peracetates. Icosa-O-acetylmaltohexaose obtained in this manner was regioselectively modified and then recycled to give novel cyclodextrins with new functions.
Synthesis is described of proposed structures (1 and 2) of lipoteichoic acid (LTA) from Streptococcus pyogenes and Enterococcus hirae, which were recently found to have immunostimulating activity. LTA is an amphiphilic molecule composed of covalently bound glycolipid and poly (glycerol phosphate). The glycolipid parts of 1 and 2 were prepared by stepwise formation of α-glycosidic bonds by use of appropriate glycosyl fluorides and then coupled with the glycerol phosphate moieties which were prepared by the phosphoroamidite procedure. Selective protection of hydroxyl groups with p-nitrobenzyl and p-pivaloylaminobenzyl groups is also described.
This review article is concerned with the recent aspects of synthetic studies on the O-glycoprotein glycans and the glycooligopeptides. Stereoselective formation of the α-glycosidic linkages between the derivatives of 2-azido-2-deoxy-D-galactopyranose, precursors of the 2-acetamido-2-deoxy-D-galactopyranosyl residue, and the protected amino acids (L-Ser or L-Thr) have been achieved through a variety of glycosylation methods. Of the glycosylated amino acids, those protected with N-Cbz, N-Fmoc, and N-Aloc groups have successfully been converted into the glycooligopeptides in solution or by solid phase methodology according to the routine programme of peptide chemistry.
The facile regio- and stereo-controlled α-glycosidations of sialic acid (Neu5Ac) are now well studied by using the thioglycosides of Neu5Ac as glycosyl donors, and suitably protected sugar residues as glycosyl acceptors. High yields of desired products are possible either by using DMTST or NIS/TfOH as thiophilic promoters in acetonitrile. A variety of gangliosides, such as GM4, GM3, GM2, GM1a, GM1b, GD1a, GD1α, GD3, lacto- and neolacto-series gangliosides, and their isomers, have systematically been synthesized by a series of reactions which start from the condensation of sialo-oligosaccharides and 2-azido-sphingosine. Various analogs and derivatives of gangliosides containing thioglycosidic linkage (s), modified sialic acids and pseudo-ceramides have also been synthesized. Recent advance in the biomedical studies using synthetic gangliosides, especially sialyl Lex and its related carbohydrate ligands, is also described.
Development of cloning techniques have made several glycosyltransferases available for organic chemists. Enzymatic synthesis of oligosaccharides using glycosyltransferases show, high regio- and stereospecific glycosidic bond formations without protecting groups of hydroxyl groups. In this review, we describe recent developments in oligosaccharide synthesis employing sialyl-, galactosyl- and fucosyltransferase, which are necessary for the synthesis of sialyl Lewis X tetrasaccharide. Application of in situ cofactor regeneration systems avoids the tedious separate preparation of sugar nucleotide, and inhibition caused by the released nucleoside mono- or diphosphates.
Most proteins within living organisms contain sugar chains. Recent advancement of cell biology has revealed that many of these sugar chains play important roles as signals for cell surface recognition phenomena in multi-cellular organisms. Based on an idea to elucidate the biological informations included in the sugar chains and introduce them as knowledge of biology, a novel scientific field called “glycobiology” was established. This review will give an outline of the structural characteristics and biosynthetic mechanism of the Asn-linked sugar chains of glycoproteins. Based on these knowledges, functional aspects of the sugar chains in the immune system of mammals, and of those of human chorionic gonadotropin will be described in order to help readers to access this new scientific field.
Glycolipids are the hybrid molecules constructing with hydrophilic carbohydrate and hydrophobic chains, and show the unique physicochemical properties and bioactivities. Their carbohydrate moieties are characteristically altered in relation to cellular proliferation, differentiation and transformation, and recently, the glycolipid associated with cellular differentiation is clarified to carry a bioactivity to induce the differentiation. Also, they have a strong immunogenecity to produce the carbohydrate-specific antibodies, which are quite useful for analyzing several biological phenomena including immune and neural systems, and for applying to diagnosis and therapy of cancers. In addition, they serve the specific receptors for bacteria, viruses, toxins, hormones and lymphokines, and modify the activities of signal transduction-mediated enzymes and cell surface antigenic proteins. Thus, recent approach on the functional analyses of glycolipids on the bases of definite structures is greatly expanded to several fields, and is summerized in this communication.
Chondroitin sulfate/dermatan sulfate-type chains and heparan sulfate/heparin-type chains represent the two major classes of glycosaminoglycan moiety (GAG) of proteoglycans. Both types of chain vary in the proportion of D-glucuronic to L-iduornic acid and the content and arrangement of the sulfate groups, thus forming diverse polymer chains with structural variability. The subjects of the present review article is to provide an overview of the structure, biosynthesis, and interactions of GAGs and to extrapolate from these reports any consensus opinions concerning the role of GAGs in various biological phenomena including cell adhesion, growth control, and activation of protease inhibitors.
We have reviewed our previous 13C NMR studies on conformational elucidation of various types of polysaccharides in the solid state based on conformation-dependent displacement of 13C chemical shifts. In general, it was shown that polymorphs of crystalline polysaccharides are readily distinguished by examination of 13C NMR spectra. Further, it is interesting to note that many kinds of polysaccaharides adopt distinct conformations as examined by 13C NMR, although they are amorphous as viewed from X-ray diffraction. In particular, we showed that three conformations, single chain, single helix, and triple helix, are present for (1→3) -β-D-glucans and -xylans of high molecular weight, depending on origin and physical treatment. It turned out that the presence of the single helix is responsible for gelation of resilient gel, antitumor activity, and activation of factor G in lymulus amebocyte lysate, although gel network of branched glucans is formed by partial association of triple-helical chains. We further studied 13C NMR studies of amylose and agarose to gain insight into gelation mechanism of these systems.