Using Carbohydrates as Nucleophiles

As already mentioned, most carbon-carbon bond forming reactions in carbohydrate chemistry use the sugar as an electrophile reacting with a carbon nucleophile. Recently, carbohydrate chemists 

The last steps of the synthesis, en route to synthon 157, consisted of chain elongation at C6 using a suitable carbanion. An acetylenic carbanion, representing C2-C3 of 151, was chosen because of a known propensity to add stereoselectively but also because they are good precursors of ketones. A brief study showed that the chelation controlled addition, that is, the use of magnesium derivatives, led to the required stereochemistry at C6. Other examples of such chelation controlled addition will be given in the following sections. 

An alternate route to prepare 2-C-gem-dimethyl branched-chain sugars involves cyclopropana-tion of a 4-C-methylene derivative followed by ring opening as used in a mycalamide synthesis [119] or in the synthesis of the C18 to C23 subunit of lasonolide A [120]. 

H3C00C 0 0CH3 H3C00C y 0 0CH3 H3COOC f o OCH3 

SCHEME 11.40 Reagents i (1) KHMDS, THE, CeCF, then D-glyceraldehyde acetonide 70% and (2) Dess-Martin periodinane 88% ii LiAlH4, Et20, 70% iii (1) NaH, BnBr, DME, 89%, (2) Dowex 50 W H+ and (3) AC2O, DMAP, CH2CI2. 

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Yoshida, T, Chika, J I, Takei, H, Asymmetric nucleophilic addition to (i- and y-alkoxy aldehydes using carbohydrate as a chiral auxiliary. Tetrahedron Lett., 39, 4305-4308, 1998. 

Polystyrene-derived phenylboronic acids have been used for the attachment of diols (carbohydrates) as boronic esters [667]. Cleavage was effected by treatment with acetone/water or THF/water. This high lability towards water and alcohols severely limits the range of reactions that can be performed without premature cleavage of this linker. Arylboronic acids esterified with resin-bound diols can be oxidatively cleaved to yield phenols (Entry 8, Table 3.36). Alcohols have also been prepared by nucleophilic allylation of aldehydes with polystyrene-bound, enantiomerically enriched allyl-silanes [668], as well as by Pummerer reaction followed by reduction of resin-bound sulfoxides [669]. 

Alpha substitutions and condensations of carbonyl compounds are some of the most common methods for forming carbon-carbon bonds. These types of reactions are common in biochemical pathways, particularly in the biosynthesis and metabolism of carbohydrates and fats. A wide variety of compounds can participate as nucleophiles or electrophiles (or both) in these reactions, and many useful products can be made. We begin our study of these reactions by considering the structure and formation of enols and enolate ions. 

Several 4-thio-D-glucofuranosylamine disaccharide derivatives such as 8 (a p, 1 3) were obtained by direct condensation of 4-thio-D-glucose with an amino-sugar. A review of the application of palladium si-allyl complexes of unsaturated carbohydrates in fuctionalization at the anomeric centre included the use of 7V-nucleophiles to provide unsaturated JV-glycosyl derivatives. Cyclic l,2-iV,0-phosphate derivatives of aldoses feature as intermediates in selective 2-0-phosphorylation reactions (see Chapter 7). 

Epoxides react faster with hydrazides than other nucleophilic functionalities such as hydroxyl, amine, carboxylic, and even thiol, which should allow for selective ligation of small molecules having hydrazide functionality (Fig. 4h). The epoxide surface was prepared from amine-coated slides immersed in a solution of poly(ethylene glycol) diglicydyl ether. Careful analysis of functional group compatibihty using carbohydrate ligands showed that the immobilization reaction was selective for hydrazides in the presence of thiols at pH > 5 [10]. Carbohydrate arrays were also prepared from imlabeled saccha-... 

The selectivity observed with hydroxyacetone (206) in proline-catalyzed aldol additions is particularly remarkable, as the scope includes a wide range of aldehydes to furnish a,/i-ketone diols such as 207 under mild conditions (Equation 19) [102]. The addition reactions of protected derivatives of a-hydrox) aldehydes as nucleophile coupling partners and aldehyde electrophiles in proline-catalyzed aldol reactions have recently been used to provide access to fragments that can be converted into a variety of carbohydrates [103). 

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