Chain Extensions of Sugars

Some methods dealing with chain extensions are reviewed in this section. Additional methods dealing with extensions at Cl are then detailed. Selected methods designed for the formation of C-glycosidic bonds, that is, for the formation of tetrahydro-pyrans or furan rings, are described in Section 11.5. 

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The methods often used for the branching of carbon chain are also suitable for the chain extension of sugars at both ends (e.g., C-l and C-5/C-6). Several developments of chain extension have recently culminated in the synthesis of long-chain carbohydrates of biological interest. 

Another very useful method for the formation of carbon-carbon bonds that also results in the chain extension of sugars is the nitromethane condensation. This reaction involves the addition of nitromethane to the reducing end of sugars under basic conditions. Subsequent treatment with... 

The use of 4,5-dihydro-2-lithio-5-methyl-l,3,5-dithiazine instead of 2-lithio-1,3-dithian gives better results in the chain extension of sugars, the former being more reactive and the products more readily desulphurized. ... 

A paper on the synthesis of enolised 2,4-diulosonic esters from chain-extension of sugars is covered in Chapter 2. 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Examples of sugar homologation based on the use of 2-lithio-l,3-dithiane (2-LDT, 13) are surprisingly rare relative to the popularity of this reagent [25]. Stereoselective chain extension of a partially protected hexose, 2,3 5,6-di-0-isopropylidene-ot-D-mannofuranose (14), into a D-glycem-D-galacto-heptose derivative (16) was reported by Paulsen and his coworkers several years ago [26] (Scheme 5). 

Schaffer398 described a synthesis of L-apiose by reaction of 170 with formaldehyde, and Horton et al,373 developed a method for extension of sugar chains through ethynylation of 170 and other aldehydo compounds by the Grignard reaction. 

The simultaneous insertion of an alkene bond and a carboxyl function into a sugar molecule is very attractive for carbohydrate chemistry in view of the further useful derivatization possible. This problem has been successfully solved by employment of the Wittig reaction, as well as its phosphonate modification (see p. 259). The compounds thus far synthesized are not numerous, although their transformations have been studied in detail and have resulted in a new method for the carbon-chain extension of carbohydrates.26... 

In further research on the carbon-chain extension of monosaccharides by reaction of free sugars with (alkoxycarbonylmethylene)-triphenylphosphoranes, Kochetkov and coworkers have reported93... 

This section presents some basic condensation reactions that result in the chain elongation of sugars. The examples presented here are historically important to the general field of carbohydrate chemistry, and include the cyanohydrin chain extension and the nitromethane condensation. 

Generally, syntheses of DAHP, KDO and Neu5Ac are based on chain extension of an appropriate sugar unit electrophiles by a C3 nucleophiles, according to the biosynthetic pathway, shown in Scheme 1. Thus, the reaction of D-erythrose 4-phosphate (13) acting as a C4 electrophile with phosphoenolpyruvate (14, C3 nucleophile) creates DAHP [6]. Mutual relationship to this pathway concerns the biosynthesis of KDO and Neu5Ac, which are produced on the reaction of phosphoenolpyruvate with D-arabinose 5-phosphate (C5 electrophile) or A-acetyl-D-mannosamine 6-phosphate (C6 electrophile), respectively [5,12]. 

Chain-extended Sugars - The application of indium- and tin-mediated Barbier-Grignard reactions in aqueous solutions to the chain-extension of... 

Diamino-2,4-dideoxy-L-arabinose and -L-ribose, 75 and 76 respectively, were obtained in similar quantities by chain extension of the L-serine-derived aldehyde 74 as shown in Scheme 17. The imino-sugar glycosylamide 78 was... 

The application of indium- and tin-mediated Barbier-Grignard reactions in aqueous solution to the chain extension of unprotected sugars has been reviewed. Some C-5 variants of iV-acetylneuraminic acid have been prepared by the indium-mediated addition of ethyl oc-(bromomethyl)acrylate to variously N-substituted mannosamines," and similar chemistry using (bromomethyl)vinyl phosphonate has led to the phosphonate analogue 12. The reaction of O-protected aldono-1,4- and -1,5-lactones with (2-bromomethyl)-acrylate or -acrylonitrile or 2-bromobutyrolactone mediated by samarium diodide led to chain-extended ulosonic acid derivatives." ... 

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