Aldonolactones

A quantitative interpretation of aldonolactone inhibition in terms of an adaptation of the active site to a transition state approaching a planar, glycosyl oxocarbonium ion is made difficult for several reasons. Due to the interconversion between the 1,4- and 1,5-lactones, and their hydrolysis to the aldonic acids, their use is limited to kinetic studies with incubation times of 10 min or less. This was not realized by most investigators prior to 1970. In many cases, only the 1,4-lactone can be isolated its (partial) conversion into... 

The question of a correlation of anomeric specificity of glycosidases with their susceptibility to aldonolactone inhibition was addressed by Reese and coworkers in a comparative study with six fungal a-D-glucosidases and... 

The results of inhibition studies with aldonolactones and 5-amino-5-deoxyaldonolactams may be summarized as follows y -D-glycosidases are inhibited by 1,5-lactones and the lactams some 100- to > 10,000-fold better than by the parent aldoses, with Kj values from 200 //Mto <0.1 nM. Al-dono-1,4-lactones are probably no better inhibitors than aldoses or polyols of comparable structure, with the possible exception s of 2-acetamido-2-deoxy-D-glucono-1,4-lactone. 

In many cases, inhibition studies were not carried out to obtain information on the reaction mechanism, but for other purposes. Thus, only inhibitors were tested that were considered suitable for the particular project, for example, studies on the biological function of the enzyme where glycosyla-mines and aldonolactones are unsuitable. Inhibition by 1,5- and 1,4-dide-... 

A number of methods has been used to assay for aldonic acids and aldonolactones. In this Section, these methods will be summarized. Comprehensive coverage of the literature related to analytical techniques has not been attempted in this article. 

Smith and coworkers152 published a relatively complete paper on the thin-layer chromatography, on silica gel, of carbohydrates of low molecular weight. Bancher and coworkers153 reported the thin-layer chromatography of degradation products of carbohydrates, including aldonic acids and aldonolactones. 

The volatility of the trimethylsilyl derivatives of the aldonolactones and related carbohydrates has made these derivatives suitable for use in mass spectrometry.161,162 Petersson and coworkers161,162 reported the mass spectra of a variety of trimethylsilyl derivatives of aldonolactones, including the spectrum of 54. 

Other derivatives of aldonolactones and alditols that have found some use in g.l.c. are trifluoroacetates156 and methyl ethers.163... 

Aldonolactones are useful starting materials for the synthesis of modified sugars. They have also been used as chiral templates in synthesis of natural products. Some of them are inexpensive, commercially available products or they may be obtained readily from the respective monosaccharides. The purpose of this chapter is to survey the main reactions of aldonolactones. Previous reviews on the subject include articles on gulono-1,4-lactones (1) and D-ribonolactone (2). Methods of synthesis, conformational analysis, and biological properties are not discussed in this chapter. 

The hydroxyl groups of aldonolactones react with a variety of aldehydes and ketones to give the corresponding acetal derivatives. Treatment of the salts of aldonic acids with benzaldehyde and hydrochloric acid or zinc chloride as catalysts give benzylidene derivatives of aldonic acids or aldonolactones (3). 

Reactions of acetal derivatives of aldonolactones involving the lactone carbonyl group or used as chiral precursors in the synthesis of noncarbohydrate natural products are discussed in later sections. 

As acylation of aldonolactones is related to -elimination reactions, the fully acylated aldonolactone derivatives are mentioned in Section IX (see also Sections VI and VIII). Only a few studies on selective acylation of aldonolactones have been described. The partially acylated derivatives have been employed as glycosylating agents or for the preparation of monometh-ylated sugars. 

Aldonolactones having their hydroxyl groups protected as ethers (mainly benzylated and silylated derivatives) have been employed for chain elongation through the carbonyl group, and therefore these type of derivatives are included in Section V. 

V. Chain Elongation Through the Aldonolactone Carbonyl Group... 

The addition of organometallic reagents to the carbonyl group of conveniently substituted aldonolactones constitutes a viable chain-extension method. The reaction leads to the formation of hemiacetals of glyculoses, 1-methylene sugars, and C-glycosyl compounds, which are precursors of, or occur as subunits of, a variety of natural products. 

Addition of lithiated heterocycles to aldonolactones yields carbon-linked nucleosides (56). Thus, the reaction of 2,3 5,6-di-O-isopropylidene-L-gu-lono-1,4-lactone (9b) or 2,3-O-isopropylidene-D-ribono-l,4-lactone (16a) with various lithiated heterocycles gave gulofuranosyl derivatives 53a-g or ribofuranosyl derivatives 54b,c. Gulonolactols 53a-g and ribonolactols 54b,c were acetylated with acetic anhydride in pyridine to yield their acetyl derivatives. The stereochemistry of compounds 53a-g and 54b,c was discussed in terms of the Cotton effect of circular-dichroism curves of the ring-opened alcohols formed upon reduction by sodium borohydride. The configuration at C-l of 53g was proved by means of X-ray analysis (57,58). 

The hemiacetals obtained by nucleophilic addition of organometallic reagents to the carbonyl group of aldonolactones may be reduced to the corresponding C-glycosyl compounds. For example, treatment of 2,3,4,6-tetra-... 

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