Disaccharides acetal formation

Acetal formation, demonstrated in the formation of the disaccharide sucrose, common table sugar. The reaction between the hydroxyl groups of the monosaccharides glucose and fructose produces the acetal sucrose. The bond between the two sugars is a glycosidic bond. 

Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids. Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention. Lactulose is also used in the treatment of hepatic encephalopathy. 

Sucrose is a disaccharide that is composed of a unit of glucose (acetal form) and a unit of fructose (ketal form) linked through C-1 of glucose and C-2 of fructose, i.e. a 1,2 link. In sucrose, neither glucose nor fructose can exist in open chain form because of the formation of acetal and ketal as shown below. As a result, sucrose is not a reducing sugar, and does now exhibit mutarotation. The specific rotation [a]D of sucrose is +66°. 

The use of complex radical donors and radical acceptors, such as carbohydrates tethered by an acetal-containing linkage, has been reported by Sinay [98]. Here, the radical addition of an anomeric radical to a 4-exo-methylene sugar derivative (compound 69) proceeds in the 8-endo mode, with formation of a eight-membered acetal ring. The end product of this reaction, after removal of the tether and acetylation, is the C-disaccharide 70 (Scheme 27). 

In general, we find that the nonreducing disaccharides give none of the carbonyl reactions observed for glucose, such as mutarotation and osazone formation, except when the conditions are sufficiently acidic to hydrolyze the acetal linkage. 

Glycosidic coupling of the acceptor 27 and the donor 23 cleanly provides disaccharide 28, in which the diphenylphosphate activation is clearly preferable to earlier methods. The a-linkage is retained exclusively due to the presence of the C2 acetate, as planned. Activation and coupling of disaccharide 28 with the protected (3-hydroxy-l-histidine derivative 29 gives the expected adduct, with an a/ 3 anomer ratio of at least 13 1. This is probably due to the low reactivity of the glycosyl acceptor, which favors formation of the more stable a-anomer. The adduct is then converted into 30, which is suitably prepared for linking with tetrapeptide S and pyrimidoblamic acid. 

In perchloric acid, hexoses and pentoses are oxidized by Ce(IV) via formation of two complex intermediates. The first is partly oxidized following Michaelis-Menten kinetics and partly dissociated to the second, which is oxidized more slowly than the former.180 The first step in the oxidation of aldoses by Tl(III) in the same medium involves the C-l-C-2 cleavage of the aldehydo form of the sugar. Thus, D-glucose gives D-arabinose and formic acid. With an excess of oxidant the final product is carbon dioxide.181 In the presence of a catalytic amount of sulfuric acid in acetic acid, Tl(III) oxidizes maltose and lactose to the corresponding disaccharide aldonic acids. The reaction showed activation enthalpies and enthropies characteristic of second-order reactions.182... 

An acetal tethered compound can easily be prepared by treatment of equimolar amounts of a 2-propenyl ether derivative of a saccharide with a sugar hydroxyl in the presence of a catalytic amount of acid. Activation of the anomeric thio moiety of the tethered compound with N-iodosuccinimide (NIS) in dichloromethane results in the formation of the p-linked disaccharide. In this reaction, no a-linked disaccharide is usually detected. It is of interest to note that when this reaction was performed in the presence of methanol, no methyl glycosides are obtained. This experiment indicates that the glycosylation proceeds via a concerted reaction and not a free anomeric oxocarbenium ion. 

The major reason that the formation of glycosides is so important is that disaccharides and polysaccharides are formed from monosaccharide units held together by gly-cosidic bonds. The oxygen of a hydroxy group from one sugar is used to form a bond to the acetal carbon of another monosaccharide. This process is discussed in Sections 25.6 and 25.7. 

Fig. 57.—Formation of cis-l,2-linked disaccharides by reactions of glycosyl dibutylstanny-lene acetals with secondary triflates.230...

Fig. 61.—Formation of a (1 — 6)-linked disaccharide by reaction of a dibutylstannylene acetals of unprotected glycosides with a glycosyl bromide.349...

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