Secondary Monosaccharides

Monosaccharides are polyhydroxy aldehydes (aldoses) or polyhydroxy ketones (ketoses). They are classified as trioses, tetroses, pentoses, hexoses, etc. according to the number of carbon atoms. With the exception of dihydroxy acetone, monosaccharides contain one or more chiral C-atoms. Most monosaccharides carry an oxygen-containing group at each carbon atom. However, there are also deoxy sugars which have one or several oxygen-free carbon atoms. 

The secondary monosaccharides differ from the primary ones in their unusual configurations at the chiral centers, by the presence of unusual deoxy groupings, methylated or acylated OH-groups, the existence of amino groupings, of branched carbon skeletons, etc. (compare the formulas in Fig. 28 and 29). Monosaccharides 

D-Glycer- Dlhydroxy-aldehyde acetone D-Erythrose D-Ribose D-Ribulose 

L-Arabinose D-Xylose D-Mannose D-Galactose D-Gulose Deoxysugars, 0-methylated and acylated sugars 

The six-membered ring of pyranoses takes on the boat conformation. Possible conformers of oc- and / -D-glucose are given in Fig. 30. Several conformers of a 

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Phase transfer conditions gave the best results in the preparation of tosylate 62 from diol 61 no chloride formation was observed. The imidazole-1-sulfonate group allowed Sn2 displacements at crowded carbon atoms by good nucleophiles under relatively mild conditions (e.g., 63 - 64). The use of primary and secondary monosaccharide triflates for modifying erythromycin and other macro-lides is referred to in Chapter 19. 

Secondary monosaccharides are formed in microorganisms, plants, and animals. 

Most secondary monosaccharides are formed from primary sugars by the following types of reactions (for biosynthesis of some secondary monosaccharides by decarboxylation of uronic acids, see D 1.2). 

Several secondary monosaccharides have a sweet taste. If present in higher concentration they attract animals involved for instance in pollination or seed dispersal (E 5.5.1 and E 5.5.2) as well as human beings (F 1). 

Easily prepared from the appropriate monosaccharide, a glycal is an unsatu-rated sugar with a C1-C2 double bond. To ready it for use in potysaccharide synthesis, the primary -OH group of the glycal is first protected at its primary -OH group by formation of a silvl ether (Section 17.8) and at its two adjacent secondary - OH groups by formation of a cyclic carbonate ester. Then, the protected glycal is epoxidized. 

Glucose and galactose enter the absorptive cells by way of secondary active transport. Cotransport carrier molecules associated with the disaccharidases in the brush border transport the monosaccharide and a Na+ ion from the lumen of the small intestine into the absorptive cell. This process is referred to as "secondary" because the cotransport carriers operate passively and do not require energy. However, they do require a concentration gradient for the transport of Na+ ions into the cell. This gradient is established by the active transport of Na+ ions out of the absorptive cell at the basolateral surface. Fructose enters the absorptive cells by way of facilitated diffusion. All monosaccharide molecules exit the absorptive cells by way of facilitated diffusion and enter the blood capillaries. 

Scheme 31. Monosaccharide derivatives obtained by oxidation at secondary hydroxyl groups using PCC in the presence of 3A or 4A MS.

In some instances, reducing sugars are present that can be reductively aminated without prior periodate treatment. A reducing end of a monosaccharide, a disaccharide, or a polysaccharide chain may be coupled to a diamine by reductive amination to yield an aminoalkyl derivative bound by a secondary amine linkage (Figure 1.96). Also see Section 4.6, this chapter, for an extensive discussion on carbohydrate modification techniques. 

The reaction of sulfuryl chloride with carbohydrates to give chloro-deoxy derivatives has been reviewed briefly in this Series.98 The reaction of sulfuryl chloride with monosaccharides has been shown to afford products in which the secondary hydroxyl groups are replaced by chlorine with inversion of configuration.68-75 Jones and coworkers reported that the reaction of methyl a-D-glucopyranoside with sulfuryl chloride and pyridine in chloroform at room temperature proceeds by way of the 4,6-bis(chlorosulfate) by an Sn2 process, with chloride as the nucleophile, to give methyl 4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside 2,3-bis(chlorosulfate).74... 

Carbohydrates mainly occur in food in the form of polymers (starches and glycogen). They are cleaved by pancreatic amylase into oligosaccharides and are then hydrolyzed by glycosidases, which are located on the surface of the intestinal epithelium, to yield monosaccharides. Glucose and galactose are taken up into the enterocytes by secondary active cotransport with Na"" ions (see p. 220). In addition, monosaccharides also have passive transport systems in the intestine. 

Primary alcohol groups in protected monosaccharides are efficiently oxidised to carboxylic acid at the nickel oxide anode. Secondary alcohol groups however react... 

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. 

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