Synthesis of carbohydrates

There are a number of factors that make carbohydrates particularly difficult to synthesise and analyse  

In order to access only the required stereoisomer, it is essential that the geometries of the glycosidic bonds are controlled. Some linkages are particularly difficult to form, for example (3-mannosidic linkages, even though they are abundant within 

Require displacement of this anomeric leaving group. 

Foruseful reviews see (a) PR Crocker and T Feizi, Curr. Opin. Struct. Biol., 1996,6,679 (b) E Flerbert, Biosci. Rep., 2000, 20, 213. 

M Mouricout, JM Petit, JR Carias and R Julien, Infect. Immun., 1990, 58, 98-106. 

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Triflates of titanium and tin are effective catalysts for various condensations of carbonyl compounds [I2I, 122, 123, 124, 125] Claisen and Dieckmann type condensations between ester functions proceed under mild conditions in the presence of dichlorobis(trifluoromethanesulfonyloxy)titaiiiuin(rV) and a tertiary amine (equations 59 and 60) These highly regio- and stereoselective condensations were used successfully m the synthesis of carbohydrates [122]... 

FIGURE 8.18 Dolichol phosphate is an initiation point for the synthesis of carbohydrate polymers in animals. The analogous alcohol in bacterial systems, undecaprenol, also known as bactoprenol, consists of 11 isoprene units. Undecaprenyl phosphate delivers sugars from the cytoplasm for the synthesis of cell wall components such as peptidoglycans, lipopolysaccharides, and glycoproteins. Polyprenyl compounds also serve as the side chains of vitamin K, the ubiquinones, plastoquinones, and tocopherols (such as vitamin E). 

As we began this chapter, we saw that photosynthesis traditionally is equated with the process of COg fixation, that is, the net synthesis of carbohydrate from COg. Indeed, the capacity to perform net accumulation of carbohydrate from COg distinguishes the phototrophic (and autotrophic) organisms from het-erotrophs. Although animals possess enzymes capable of linking COg to organic acceptors, they cannot achieve a net accumulation of organic material by these reactions. For example, fatty acid biosynthesis is primed by covalent attachment of COg to acetyl-CoA to form malonyl-CoA (Chapter 25). Nevertheless, this fixed COg is liberated in the very next reaction, so no net COg incorporation occurs. 

Even though acetate units, such as those obtained from fatty acid oxidation, cannot be used for net synthesis of carbohydrate in animals, labeled carbon from " C-labeled acetate can be found in newly synthesized glucose (for example, in liver glycogen) in animal tracer studies. Explain how this can be. Which carbons of glucose would you expect to be the first to be labeled by "Relabeled acetate ... 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

Biological Synthesis of Carbohydrates. Third Frankland Memorial Lecture, J. R. Inst. Chem., 79 (1956)591-592. 

Nowadays, a strategic area of research is the development of polymers based on carbohydrates due to the worldwide focus on sustainable materials. Since the necessary multi-step synthesis of carbohydrate-based polymers is not economical for the production of commodity plastics, functionalization of synthetic polymers by carbohydrates has become a current subject of research. This aims to prepare new bioactive and biocompatible polymers capable of exerting a temporary therapeutic function. The large variety of methods of anchoring carbohydrates onto polymers as well as the current and potential applications of the functionalized polymers has been discussed recently in a critical review [171]. Of importance is that such modification renders not only functionality but also biodegradability to the synthetic polymers. 

Acetal handle 78 synthesized from Merrifield resin and 4-hydroxy-benzaldehyde was applied to the solid-phase synthesis of carbohydrates and 1-oxacephams (Scheme 41) [90]. For the latter, a 1,3-diol was initially anchored to the support to form a cyclic acetal. A ring opening reaction with DIBAL generated a resin-bound alcohol which was converted to the corresponding triflate for A-alkylation with 4-vinyl-oxyazetidin-2-one. A Lewis acid catalyzed ring closure released 1-oxa-cephams from the support. 

M. Dubber and T. K. Lindhorst, Synthesis of carbohydrate-centered oligosaccharide mimetics equipped with a functionalized tether, J. Org. Chem., 65 (2000) 5275-5281. 

N. Jayaraman and J. F. Stoddart, Synthesis of carbohydrate-containing dendrimers. 5. Preparation of dendrimers using unprotected carbohydrates, Tetrahedron Lett., 38 (1997) 6767-6770. 

The initial conversion of light into chemical energy takes place in the thylakoid membrane. Besides the chlorophylls and series of electron carriers, the thylakoid membrane also contains the enzyme adenosine triphosphate (ATP) synthase. The enzymes that are responsible for the actual fixation of C02 and the synthesis of carbohydrate reside in the stroma that surround the thylakoid membrane. The stroma also contains deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and ribosomes that are essential for protein synthesis [37]. 

Atrazine enters plants primarily by way of the roots and secondarily by way of the foliage, passively translocated in the xylem with the transpiration stream, and accumulates in the apical meristems and leaves (Hull 1967 Forney 1980 Reed 1982 Wolf and Jackson 1982). The main phytotoxic effect is the inhibition of photosynthesis by blocking the electron transport during Hill reaction of photosystem II. This blockage leads to inhibitory effects on the synthesis of carbohydrate, a reduction in the carbon pool, and a buildup of carbon dioxide within the leaf, which subsequently causes closure of the stomates, thus inhibiting transpiration (Stevenson et al. 1982 Jachetta et al. 1986 Shabana 1987). 

Fig. 8. First synthesis of carbohydrate-substituted polymers by ROMP using a defined orga-nometallic initiator. Grubbs synthesis of glucosamine-substituted polymers...

For the synthesis of carbohydrate-substituted block copolymers, it might be expected that the addition of acid to the polymerization reactions would result in a rate increase. Indeed, the ROMP of saccharide-modified monomers, when conducted in the presence of para-toluene sulfonic acid under emulsion conditions, successfully yielded block copolymers [52]. A key to the success of these reactions was the isolation of the initiated species, which resulted in its separation from the dissociated phosphine. The initiated ruthenium complex was isolated by starting the polymerization in acidic organic solution, from which the reactive species precipitated. The solvent was removed, and the reactive species was washed with additional degassed solvent. The polymerization was completed under emulsion conditions (in water and DTAB), and additional blocks were generated by the sequential addition of the different monomers. This method of polymerization was successful for both the mannose/galactose polymer and for the mannose polymer with the intervening diol sequence (Fig. 16A,B). 

As had been observed in the synthesis of carbohydrate-substituted polymers of different lengths, the reactivity of the monomers was an important parameter in generating the triblock polymers. If the mannose-substituted 7-oxanor-bornene derivative was first polymerized, followed by the galactose-derivatized norbornene and the mannose-substituted norbornene monomers, two distinct sets of products were observed. These were identified by modification of the resulting polymers by acetylation, and analysis of the products by GPC. With this protocol, it was found that the product was composed of short polymers (DP=... 

Scheme 13.21 Solid-phase synthesis of carbohydrate bound glycopeptides.

L. K. Sydnes and S. Valdersnes 2137 Recent advances in the synthesis of carbohydrate analogs... 

Corticosteroids are produced by the adrenal glands, and display two main types of biological activity. Glucocorticoids are concerned with the synthesis of carbohydrate from protein and the deposition of glycogen in the liver. They also play an important role in inflammatory processes. Mineralocorticoids are concerned with the control of electrolyte balance, promoting the retention of Na+ and CC, and the excretion of K+. Synthetic and semi-synthetic corticosteroid drugs are widely used in medicine. Glncocorticoids are primarily nsed for their antirhenmatic and anti-inflammatory activities, and mineralocorticoids are nsed to maintain electrolyte balance where there is adrenal insufficiency. 

For a recent review on the organocatalytic synthesis of carbohydrates, see Limbach, M. Chem. Biodiv. 2005, 2, 825-836. 

Stereoselective Synthesis of Carbohydrates from Acyclic Precursors... 

Note This chapter is part 31 in the series, De N[Pg.182]

For the generation of several contiguous chiral centers, two alternative key step reactions can be applied (i) stereoselective CC-bond formation and (ii) stereoselective functionalization of compounds having already the required carbon skeleton. In the de novo-synthesis of carbohydrates and related natural products via inverse-type hetero-Diels-Alder reactions both of these principles are especially well documented as will be shown below (8-10). ... 

The scope of this cycloaddition reaction was very promising. Subsequently, removal of the CC-double bond and stereoselective functionalizations at positions 4 and 5 (carbohydrate numbering) was investigated for the synthesis of carbohydrates and related natural products, to provide C-3 branched carbohydrate derivatives (or C-4 heteroatom substituted derivatives after carbon/he-teroatom exchange reactions). However, the desired hydrogenation of such systems with various hydrogen donors has mainly resulted in low yields and/or side reactions due to the inherent stability of the formal CC-double bond (12., 15). ... 

Synthesis of Carbohydrates and Derivatives from 7-Oxanorbornenes ( Naked Sugars )... 

Preparations of the "naked sugars" and their application to the synthesis of carbohydrate derivatives and other natural products are presented below. 

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