Carbohydrate-derived carbonyl reactions

Analytical Use of Fluorescence-Producing Reactions of Lipid- and Carbohydrate-Derived Carbonyl Groups with Amine End Groups of Polyamide Powder... 

Photochemical Cycloaddition Reactions between Unsaturated Carbohydrate Derivatives and Carbonyl Compounds... 

Reactions of Excited Carbonyl Croups in Carbohydrate Derivatives with Solvent Molecules... 

Cycloaddition Reactions between Excited Carbonyl Groups in Carbohydrate Derivatives and Unsaturated, Non-Carbohydrates... 

The chemical transformations of dialkyl dithioacetals have been reviewed in detail [47] and offer routes to a variety of useful carbohydrate derivatives. Dialkyl dithioacetal derivatives of sugars continue to play an important role in modem synthetic carbohydrate chemistry through reactions of die dithioacetal function and manipulation of the sugar hydroxyl groups. Dithioacetals also provide a convenient method for temporary protection of sugar carbonyl groups in the synthesis of noncarbohydrate natural products. 

Otherwise, unsaturation may be introduced by use of carbonyl-containing carbohydrate derivatives and carbon nucleophiles that contain alkene (or, if desired, alkyne) functionality, a notable illustration being the tin-or indium-mediated C-l allylation of unprotected sugars. As an illustration, D-arabinose, treated with allyl bromide in aqueous ethanol in the presence of tin gives, after acetylation, 278 in 85% yield.258 In this procedure aldoses react better than do ketoses, and pentoses better than hexoses. More usual is the use of Grignard reactions to give, for example, the octynes 279. 

L-Proline catalyzes the aldol reaction. This approach has been applied to the synthesis of carbohydrate derivatives as illustrated by the glucose derivative 7 (Fig. 11) (237). The three-component Mannich reaction can be used to prepare p-amino and p-amino a-hydroxy carbonyl compounds in a single step (Fig. 12) (233). As with other types of catalysts, organocatalysts can be immobilized to aid recovery (253). 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

Finally, carbohydrate ligands of enantioselective catalysts have been described for a limited number of reactions. Bis-phosphites of carbohydrates have been reported as ligands of efficient catalysts in enantioselective hydrogenations [182] and hydrocyanations [183], and a bifunctional dihydroglucal-based catalyst was recently found to effect asymmetric cyanosilylations of ketones [184]. Carbohydrate-derived titanocenes have been used in the enantioselective catalysis of reactions of diethyl zinc with carbonyl compounds [113]. Oxazolinones of amino sugars have been shown to be efficient catalysts in enantioselective palladium(0)-catalyzed allylation reactions of C-nucleophiles [185]. 

Several diastereoselective HDA (hetero-Diels-Alder) reactions of a,/3-unsaturated carbonyl compounds and electron-rich alkenes have been exploited to gain carbohydrate derivatives with good diastereomeric excess. In HDA reaction, up to three chiral centers are formed with high stereoselectivity at each chiral carbon [78]. 

Carbohydrate-derived enones have been employed as chiral, electrophilic alkenes in addition reactions to alcohols, ethers, or aldehydes90. Through benzophenone-sensilized photochemical initiation, hydrogen abstraction occurs from the a-carbon atoms in alcohols and ethers or from the carbonyl atom in aldehydes. Addition then occurs exclusively on the /(-face of the enone,... 

Coupling of lactones and ketones. Sml2 in THF/HMPA effects coupling of a carbohydrate-derived lactone such as 1 and a ketone that involves oxygenation of 1 followed by a carbonyl addition reaction with high diastercosclcctivity. 

The imine formed on hydrolysis yields o-phenylenediamine and the corresponding carbonyl compound, and, depending on the pH of the medium, can also undergo further chemical and electrochemical reactions. By this reduction of carbohydrate derivatives of quinoxaline, the corresponding deoxy saccharides would be formed. For 1,2-dihydro-2,3-dimethylquinoxaline in an alkaline medium, the decrease in the height of wave i2 and the appearance of an anodic wave, ia, with increasing pH value prove that only its protonated form is reduced to the corresponding quinoxaline derivative, whereas its nonprotonated form is capable of oxidation to the initial 2,3-dimethylquinoxaline, as shown in Scheme 13. 

A text on aspects of asymmetry in carbohydrates has appeared, which includes reviews on the composition of reducing sugars in solution, asymmetric reactions of carbohydrates containing carbonyl groups, and prochirality and pseudoasymmetry in carbohydrate biochemistry, besides articles on nitro-sugar stereochemistry, chiral sulphur derivatives, and carbohydrate crown-ether compounds. A general survey of organic chemistry includes an extensive account of monosaccharide chemistry. ... 

Similarly, carbohydrates often exist in an equilibrium between a cyclic h niacetal form and a carbonyl form with the latter in an extremely low quantity (14). Therefore, for alkylation of carbohydrate derivatives in organic solvent, extensive functional group transformation and derivatization is required to generate the desired carbonyl. However, in the aqueous reaction, the hemiacetal-form and the carbonyl form is in a constant equilibrium. And the carbonyl form will react, which drives the equilibrium until all the starting material has reacted (eq. 7). 

Regioselective reductions of a,P-imsaturated ketones were performed in water containing carbohydrate-derived amphiphiles. Cyclohexenones were converted to allylic alcohols, whereas cyclopentenones gave substantial amounts of 1,4-reduction (Denis et al, 1996). Such a use of concentrated aqueous solutions of carbohydrates as the reaction medium has been described by Lubineau (1993, 1994b) in the context of many different chemical transformations including Diels-Alder, aldol and Michael reactions, as well as reductions of a,p-unsaturated ketones, all dealing with the chemistry of the carbonyl group either as the reaction site or as the activation site (Scheme 4.17). 

Sulfonic acid esters are more versatile than carboxylic acid esters due to their stability toward acids and bases and the way they are cleaved. Cleavage of carboxylic acid esters occurs by carbonyl-oxygen fission (reaction 4.11), while cleavage of sulfonic acid esters occurs by alkyl-oxygen fission (reaction 4.12). This latter chemical property makes them very useful in the synthesis of many carbohydrate derivatives and analogues in which the nucleophile is substituted onto the carbon atom of the carbohydrate. 

The basic carbohydrate molecule possesses an aldehyde or ketone group and a hydroxyl group on every carbon atom except the one involved in the carbonyl group. As a result, carbohydrates are defined as aldehyde or ketone derivatives of polyhydroxy alcohols and their reaction products. A look at the formula for glucose shows that it contains hydrogen and oxygen atoms in the ratio in which they are found in water. The name carbohydrate... 

Hydrazide groups can react with carbonyl groups to form stable hydrazone linkages. Derivatives of proteins formed from the reaction of their carboxylate side chains with adipic acid dihydrazide (Chapter 4, Section 8.1) and the water-soluble carbodiimide EDC (Chapter 3, Section 1.1) create activated proteins that can covalently bind to formyl residues. Hydrazide-modified enzymes prepared in this manner can bind specifically to aldehyde groups formed by mild periodate oxidation of carbohydrates (Chapter 1, Section 4.4). These reagents can be used in assay systems to detect or measure glycoproteins in cells, tissue sections, or blots (Gershoni et al., 1985). 

Carbohydrate lactones have been used as the carbonyl reagent in the Reformatsky reaction. Thus, 2,3 5,6-di-O-cyclohexylidene-D-mannono-1,4-lactone [44, obtained by oxidation of the mannofuranose derivative (49)] reacted with ethyl bromoacetate and zinc to give the protected 2-deoxy-3-octulosonic acid ethyl ester (45a) in 69% yield (50). Ketonic hydrolysis with potassium hydroxide in aqueous methanol, followed by acidification and heating, afforded the 1-deoxyheptulose derivative 45b. Similarly, starting from compound 44, the 1-C-substituted allyl and propar-gyl lactols were prepared on reaction with allyl or propaigyl bromides in the presence of zinc (51). 

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