Uronic Acid Derived Lactones

The occurrence of uronic acid provides another means of easy access to bicyclic lactones, which can be used for the synthesis of various targets, such as surfactants or pseudo glycopeptides. 

In a similar manner, sialic acids are liable to lactone formation. In some cases the observed lactones have been suggested to possess enhanced biological 

Under various acetylation conditions, sialic acid leads to either 1,4-lactone 

117 and 121. These compounds were designed as potential sialidase inhibitors [161, 167]. 

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Reactions between D-glucuronic acid, its amide, or 6,3-lactone with various aromatic and aliphatic amines, carbamates, and their derivatives, have often been used for the preparation of (D-glucosyl-amine)uronic acid derivatives of interest as potential drug metabolites or chemotherapeutic agents however, very little evidence is available... 

The vast majority of animals and plants are able to synthesize vitamin C through a sequence of four enzyme-driven steps, which convert D-glucose to vitamin C (Fig. 12.6). In eukaryotes, vitamin C biosynthesis occurs via two highly divergent biochemical pathways. In rats and other mammals, glucose is converted into L-gulono-1,4-lactone via a complex pathway involving uronic acid derivatives and... 

Types I to IV were 7-lactones of aldonic acids, Types V and VI were uronic acid derivatives with the same basic configuration as Types I and II, respectively. 

Scheme 30 Bolaphiles derived from uronic acid 6,3-lactones...

Lactones derived from carbohydrates are building blocks of high synthetic potential. Next to the readily available aldonolactones and uronic acid lactones, some bicyclic systems have recently emerged as useful synthons. Examples of applications encompass functional derivatives such as polymers, as well as more elaborated compounds of physico-chemical or biological relevance. 

In the carbohydrate series, the acids encountered are aldonic, aldaric, uronic, or saccharinic acids. Often, these acids are readily transformed into their lactones or methyl esters, and it is as derivatives of these that they are commonly studied. Table VIII (see p. 136) records examples in which derivatives of such acids and lactones have been subjected to gas-liquid chromatography. 

In model experiments,205 it was found that concentration of an aqueous solution of the aldonic acids in the presence of hydrochloric acid gives exclusively the 1,4-lactones, which, on subsequent trimethyl-silylation, give only one peak on the chromatogram. This method was successfully employed for the separation of D-galacturonic, D-glucuronic, and D-mannuronic acids. Of the 1,4-lactones examined, only the trimethylsilyl ether of D-mannono-1,4-lactone was obtained in crystalline form. However, all of the derivatives showed characteristic differences in their infrared spectra in the range of 1500 to 600 cm"1. When this method was applied to the determination of uronic acids in a variety of polysaccharides,205 it was impossible to find any hydrolytic conditions under which the uronic acids were quantitatively released and then reduced, a problem experienced by other workers.20 The method was, however, successful in affording a qualitative, microscale procedure for the identification of hexuronic acids (which otherwise are difficult to detect). 

Norman has tabulated the constants for various derivatives of the uronic acids and has summarized previous work on their identification. The free acids or their lactones have been used for the purpose of identification. The quinine, brucine, and cinchonine salts" have also been used for this purpose, although their isolation in pure form is hindered by the presence of the corresponding alkaloidal salts of the low polymers of the acid. Some of the complex hydrazines have been used to identify the acids. p-Bromophenylhydrazine has been frequently used for this purpose. One difficulty in the use of hydrazines is that they may form numerous types of derivatives such as salts, hydrazides, hydrazones and osazones. 

Chromatographic methods have also been developed for quantitative determination of the AUC of pectin. Uronic acids have been analyzed using gas-liquid chromatography (GLC) after conversion to L-galactono-1,4-lactone via potassium borohydride reduction and lactonization using methanolic hydrogen chloride. The derived lactone was then analyzed by GLC as the trimethylsilyl derivative (Perry... 

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