In these years, much interest has been focused on the synthesis of monosaccharides starting from the simple organic molecules, with the development of various highly stereoselective carbon-carbon bond forming reactions of acyclic system. And, recently, convenient syntheses of a variety of monosaccharides are reported using 2, 3-O-isopropylidene-D-glyceraldehyde as 3-carbon building block. Further, a new and potentially useful chiral 4-carbon building block for the L-sugar, 4-O- benzyl-2, 3-O-isopropylidene-L-threose are prepared starting from L-tartaric acid and biologically important L-sugars are also successfully synthesized. Several new glycosylation reactions, which proceed under mild reaction conditions with high stereoselectivity, are exploited; namely, i) the glycosyl fluoride method, ii) the glycoside synthesis by the stereoselective internal cyclizations, and iii) by the direct introduction of alkoxy group to α-position of keto function of sugar.
This article critically reviews the reactivity of hydroxyl groups in mono-saccharides toward direct acylation and describes the method of regioselective modifications (acylation, alkylation, etc) of a hydroxyl group without blocking-deblocking technique via cyclic tin intermediates. O-Acyl migration in mono-O-acyl derivatives of D-glucose and L-arabinose under various conditions is also discussed.
A regio- and stereo-controlled synthesis of a sulfated glyceroglycolipid 1 is described. A key glycosyl acceptor 3 was prepared in a regioselective way by use of a dibutylstannylene intermediate. A key glycosyl donor 2 was synthesized in a stereocontrolled way by use of allyl, benzyl, and monochloroacetyl groups as the protective groups for the D-glucosyl residue. The key glycosidation between 2 and 3 could be achieved in a stereoselective way in the presence of AgOSO2CF3 to give 26 with the desired stereochemistry. Further transformation of 26 into 1 could be performed via 28 obtained by a regioselective deprotection of the acyl groups.
The utility of carbohydrates for stereospecific total syntheses of natural products is illustrated : (1) total syntheses of 16-membered-ring macrolide antibiotics (A 26771 B, carbomycin B, josamycin and tylosin) from D-glucose ; (2) total syntheses of pyrrolizidine alkaloid necine bases (rosmarinecine, 7-deoxyrosmarinecine and isoretronecanol) from D-glucosamine.
Bacterial surface substance has been known to possess the endotoxic activity which is located at the lipid A part. Although a chemical structure for lipid A was early proposed, exact positions of fatty acids linked to the disaccharide skeleton have been ambiguous. We succeeded to obtain a chemically pure sample of natural E. coli mutant lipid A. From results obtained by 2 D-NMR analysis of this sample, we proposed a revised structure for lipid A. 2, 2'-N, 3, 3'-O-Tetraquis [(R) -3-hydroxytetradecanoyl] -β (1-6) -D-glucosamine disaccharide 1, 4'- diphosphate synthesized according to the proposed structure was quite identical with the natural acidic precursor of lipid A. This is the first achievement to establish the correct chemical structure of the natural lipid A by organic synthesis.
The chemistry and biological activities of orthosomycins, which contain the characteristic orthoester interlinkage between component monosaccharides, and recent developments in the construction of the linkage were reviewed.
Recent studies on the nucleic acid-cleaving reaction and in vitro virus-inactivating action of 1, 2-enediol reductones and some reducing carbohydrate derivatives are reviewed. After a brief discussion on the mechanism of oxygen radical formation from 1, 2-enediols, works on the autoxidation of reducing sugars are reviewed, followed by the demonstration of examples of nucleic acid cleavages by reductones, sugar phosphates, aldopentoses, pyranosiduloses and synthetic and natural oxidized polysaccharides. In vitro inactivation of viruses by ascorbic acid, triose reductone, aldopentoses and partially substituted reducing sugars including some new types of synthetic polysaccharides in the presence or absence of Cu2+ are discussed. A table of compounds with DNA cleaving ability and recent reviews on nucleic acid breakage by oxygen radicals are included with 138 cited literatures.
Sialic acid as constituents of glycoproteins, glycolipids, and oligosaccharides plays an important role in many animal cells. N-Acetylneuraminic acid (NANA), the most important sialic acid was crystallized to fine needles (A) and prisms (B) from the different solvents used for recrystallization. The anomeric configuration of both crystals was confirmed as the β-configuration at C-2 position. Syntheses of various kind of NANA derivatives are reported in this article. Methyl 2-chloro-4, 7, 8, 9-tetra-O-acetyl-N-acetyl-β-D-neuraminate (5) was prepared from methyl N-acetyl-β-D-neuraminate (4) in a good yield. From the chloride, mucin analogs, sialyllactose, monosaccharide and disaccharide nucleoside analogs were synthesized. Confirmation of the stereochemistry at C-2 position Of NANA of these products was reported by NMR and hydrolysis experiments.
There are several ways to introduce fluorine into carbohydrates. Some typical fluorinations are 1) the reaction of diethylaminosulfur trifluoride (DAST) or tetrabutylammonium fluoride (TBAF) with the hydroxyl or sulfonylated hydroxyl groups, respectively, 2) ring opening of the oxirane or epimine with the olah reagent or potassium hydrogen fluoride (KHF2), 3) addition of fluoroxytrifluoromethane (CF3OF), acetyl hypofluorite (CF3CO2F), or xenon difluoride (XeF2) to the vinyl ethers (for example, glycals), 4) fluorination of carbonyl compounds with DAST or F-containing Wittig reagents, and 5) substitution of active groups by fluorine with appropriate reagents. For structural elucidation of the fluorinated carbohydrates, 19F-NMR spectroscopy gives a very useful tool by showing rather simple signal pattern in comparison to that of the 1H-NMR spectrum of the same compound. The 3JH, F values, which vary greatly with the : change of the stereo- and electro-chemical environments, are also useful.
This article describes synthetic methods for constituent mono-and oligo-saccharides existing in asparagine-linked glycan of glycoprotein. The target compounds are L-fucose, N-acetyllactosamine, di-N-acetylchitobiose, core pentasaccharide, and, di-and tri-mannopyranosyl-N-acetylglucosamines. Scope and limitation of chemical syntheses of oligosaccharides are generally discussed. Most of this article is based on the papers reported from this laboratory since 1979.
Synthesis of polysaccharides by ring-opening polymerization of anhydro-sugar derivatives is reviewed. Ring-opening polymerizations of various anhydro-sugar derivatives give many kinds of polysaccharides. Polymerization mechanism and the polymer structure depend on the monomer structure and polymerization conditions. For example, in the polymerization of 1, 4-anhydro-sugar derivatives, the D-ribose monomer affords a stereoregular (1→4) -β-D-ribopyranan and a stereoregular (1→5) -α-D-ribofuranan, while the L-arabinose monomer is not polymerized stereoregularly. Most of 1, 6-anhydro-sugar derivatives are polymerized with cationic catalysts at low temperatures, giving highly stereoregular polysaccharides some of which have a functional group regioselectively. Synthetic polysaccharides are expected to reveal some physiological activities.
This review deals with. the recent advances in the chemical modification of chitin and also some properties of the resulting derivatives. The reactions discussed here are (1) deacetylation to chitosan and some reactions on chitosan, (2) acylation, (3) glycolation, (4) carboxymethylation, (5) sulfation, and (6) miscellaneous reactions.
Research on syntheses and functions of polymers consisting of carbohydrate and noncarbohydrate moieties is now expanding rapidly. An advance in the field is attributable to discoveries of important biological roles of carbohydrates, developments of chemical and physical methods and techniques for separation, analysis, and synthesis, as well as demand for effective utilization of renewable resources. The present review deals with three different types of the polymers : (1) Modified polysaccharides. Discussion is focused on regioselectivities of chemical modifications. (2) Polymers containing carbohydrates in the main chain. Recently developed routes for condensation polymers and block copolymers are described. (3) Polymers having pendant carbohydrates. Polymer-supported carbohydrates are used as intermediates in the syntheses of carbohydrates and as potential chiral templates. Linear, soluble polymers are also of interest as amphiphilic polymers capable of binding organic solutes in water and as tools for examination of bioorganic mechanisms and for pharmacological applications. Oligosaccharide-containing polymers are expected to play a role in recognition, acting as receptors for lectins, enzymes, proteins, hormones, and viruses.
Pullulan is a natural polysaccharide with a linear structure comprising repeating α-1, 6-linked maltotriose molecules which elaborated by a black yeast, Aureobasidium pullulans. Pullulan, a tasteless, oderless, and edible white fine powder, is a natural glucan as are amylose, dextran, and cellulose, but dissolves readily in cold water to form a viscous, non-gelling, aqueous solution. The features of pullulan, superior to those of other polysaccharides, provide pullulan as an excellent adhesive, binder, thickener, viscosity stabilizer and coating agent for food application. Pullulan films prepared with aqueous solution are edible and oxygen impermeable. Besides the food industry, pullulan is widely used in pharmaceutical, biotechnical and other industries.
The application of carbohydrates as surfactants and conditioning reagents to cosmetics, toiletries, and related fields is reviewed. Surfactant properties of carbohydrate derivatives are discussed especially in relation between molecular structure and HLB value. Bio-origin surfactants, such as those from sophoroplipids available from T. bombicola fermentation, are being developed and its situation is explained. Recent progress in hair conditioning and skin moisturization is discussed.
Recently, we have seen remarkable progress in the enzymology and in the technological applications of enzymes to starch industry. By the end of 1960, the dextrose production of Japan was swiftly switched from the acid hydrolysis to the enzymatic hydrolysis method. Besides dextrose and syrup, at present, isomerized syrups, maltitol, cyclodextrins, coupling sugar and maltooligosaccharides are utilized and employed for other many purposes. Present pictures of starch hydrolyzing industry in Japan are mentioned in this paper.
The cellulose derivatives are used as the additive in the pharmaceutical preparation with various active ingredients, mainly as a binder or film coating agent of the tablets, granules and other dosage forms. Recently the safety and availability of the drug come to be regarded as important, then the development of new application method and function is required for high polymers. This review is concerned with the syntheses, properties and applications of various cellulose derivatives for pharmaceutical use as additive.