Five-membered rings, sugars

The oxide ring is six-membered in some sugars and five-membered in others, and it is helpful to use names that indicate the ring size. The five- and six-membered oxide rings bear a formal relationship to oxa-2,5-cyclohexadiene and oxa-2,4-cyclopentadiene that commonly are known as pyran and furan, respectively ... 

The backbone of a nucleic acid is a polymer of ribofuranoside rings (five-membered rings of the sugar ribose) linked by phosphate ester groups. Each ribose unit carries a heterocyclic base that provides part of the information needed to specify a particular amino acid in protein synthesis. Figure 23-21 shows the ribose-phosphate backbone of RNA. 

These sugars have five-membered rings. Four of the ring atoms are planar, but either carbon atom 2 or carbon atom 3 (with attached H and OH) points upward or downward from the planar ring atoms. 

In a similar manner, ketones can react with alcohols to form hemiketals. The analogous intramolecular reaction of a ketose sugar such as fructose yields a cyclic hemiketal (Figure 7.6). The five-membered ring thus formed is reminiscent of furan and is referred to as a furanose. The cyclic pyranose and fura-nose forms are the preferred structures for monosaccharides in aqueous solution. At equilibrium, the linear aldehyde or ketone structure is only a minor component of the mixture (generally much less than 1%). 

The well-known reaction leading to ring expansion of cyclic ketones has been applied to derivatives of oxo sugars in an attempt to develop a new route to novel deoxy sugars. By treatment with diazomethane both a five-membered (42) and a six-membered (26) sugar ring have been expanded by insertion of a methylene group. 

Furanose (Section 25.5) The five-membered-ring form of a simple sugar. 

DNA is a polymer with a backbone built of repeating units derived from the sugar ribose (20). For DNA, the ribose molecule has been modified by removing the oxygen atom at carbon atom 2, the second carbon atom clockwise from the ether oxygen atom in the five-membered ring. Therefore, the repeating unit—the monomer—is called deoxyribose (21). 

Cyclic hemiacetals or hemiketals of sugars with a five-membered (tetrahydrofuran) ring are called furanoses, those with a six-membered (tetrahydropyran) ring pyran-oses. For sugars with other ring sizes see 2-Carb-5. 

The chelate ring size principle can have structural effects as well as effects on thermodynamic stability in aqueous solution. An example is coordination of metal ions by sugars (44). The cyclic polyol cts-inositol can coordinate metal ions in two distinct ways (Fig. 14) (45). In ax-ax-ax bonding (Fig. 14), the metal ion is part of three fused six-membered chelate rings. Alternatively, in ax-eq-ax coordination, the metal ion is part of two fused five-membered and one six-membered chelate rings. Angyal has noted that metal ions of radius more than 0.8 A adopt the ax-eq-ax structure (44), whereas with an ionic radius... 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

The second- and oldest-method for the preparation of thionocarbamates on carbohydrate scaffolds consists of the condensation of thiocyanic acid, generated in situ from potassium thiocyanate and a protic acid, with an anomeric-free sugar to form the thermodynamically more stable five-membered ring OZT as the major compound (Scheme 2).27,28... 

The enzymatic synthesis of sucrose also throws light on the formation of the furanose form of fructose in the sucrose molecule. The fact that sucrose is directly formed from D-glucose-l-phosphate and D-fructose supports Isbell and Pigman s34 and Gottschalk s85 evidence that the latter monosaccharide occurs in solution in an equilibrium mixture of furanose and pyranose forms. This makes it unnecessary to postulate a special mechanism of stabilization of a five membered (furanose) ring before the formation of compound sugars containing the D-fructose molecule.86... 

A number of examples involving the stereochemistry of five membered rings are met in furanose sugars. An interesting example is that of 2, 5 dimethylcyclopentane 1, 1 dicarboxylic acid. This acid can exist in two geometrically isomeric forms which can be distinguished by decarboxylation. The cis xxvii isomer forms two monocarboxylic acids which are meso because they possess a vertical plane of symmetry. The trans isomer xxviii forms only one monocarboxylic acid and since it possesses no elements of symmetry, therefore, exists in optically active forms and a meso variety. 

The reactivity of carbohydrates is dominated by the reactivity of the aldehyde group and the hydroxyl on its next-neighbor (/ ) carbon. As illustrated by the middle row of Fig. 2.3, the aldehyde can be isomerized to the corresponding enol or be converted into its hydrate (or hemiketal) form upon reaction with water (or with an hydroxyl-group). These two reactions are responsible for the easy cycliza-tion of sugars in five- and six-membered rings (furanose and pyranose) and their isomerization between various enantiomeric forms and between aldehyde- and ketone-type sugars (aldose and ketose). 

FIGURE 11.7 Cardiac glycosides consist of a sugar, a steroid skeleton, and a lactone ring. A five-membered lactone ring as here occurs in the cardenolide type. 

Both six-membered pyranose and five-membered furanose structures are encountered, a particular ring size usually being characteristic for any one sugar. Thus, although glucose has the potential to form both six-membered and five-membered rings, an aqueous solution consists almost completely of the six-membered hemiacetal form five-membered rings... 

Sucrose is composed of glucose and fructose, and again we have a six-membered pyranose ring coupled to a five-membered furanose ring. However, there is a significant difference when we compare its structure with that of lactulose in sucrose, the two sugars are both linked through their anomeric... 

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