Cyclic Forms of Sugars

Write a mechanism for the mutarotation of glucose catalyzed by base. Solution 

Predict the product(s), including stereochemistry, of each of the following processes and show the mechanism for the reactions  

Salicin, isolated from willow bark Solutions 

---

Note. In cyclic forms of sugars, the configuration at the anomeric chiral centre is defined in relation to the anomeric reference atom (see 2-Carb-6.2). 

However, as we shall see shortly, Fischer-projection-derived eclipsed conformers are particularly useful in deducing the stereochemistry in cyclic forms of sugars (see Box 3.16). 

The addition of an amine to the carbonyl group of an aldehyde yields—after removal of water—an aldimine (not shown see p. 178). Aldimines are intermediates in amino acid metabolism (see p. 178) and serve to bond aldehydes to amino groups in proteins (see p. 62, for example). The addition of an alcohol to the carbonyl group of an aldehyde yields a hemiacetal (R-O-C(H)OH-R). The cyclic forms of sugars are well-known examples of hemi-... 

Anomers Diastereomers of glycosides, hemiacetals, or related cyclic forms of sugars, differing in configuration only at C-1 of an aldose, C-2 of a 2-ketose, etc. 

Sugars exist predominantly as cyclic molecules rather than in an open-chain form. Haworth projection formulas are more realistic representations of the cyclic forms of sugars than are Fischer projection formulas. Many stereoisomers are possible for five- and six-carbon sugars, but only a few of the possibilities are encountered frequently in nature. 

Recall Why are furanoses and pyranoses the most common cyclic forms of sugars ... 

Anomers. Diastereomers of glycosides or related cyclic forms of sugars that are specifically epimers at the anomeric carbon (C of an aldose, or C2, C3, etc., of a ketose). 

How can we represent the stereochemistry of the cyclic forms of sugars One approach uses Fischer projections. We simply draw elongated lines to indicate the bonds formed npon cyclization, preserving the basic grid of the original formula. Be careful not to confnse the three new apices of the ensning rectangle with carbon atoms. 

In general, hemiacetals exist only in solution and cannot be isolated because they easily decompose back to the component alcohol and aldehyde or ketone. However, some cyclic hemiacetals are more stable. For example, cyclic forms of sugar molecules are hemiacetals. 

If a cyclic form of a sugar is to be represented in the Fischer projection, a long bond can be drawn between the oxygen involved in ring formation and the (anomeric)... 

One of the more difficult problems encountered in obtaining a valid assay of formic acid is that of formate ester formation. The formate is derived from the cyclic, hemi-acetal structure which is an equilibrium form of many free sugars in solution. For example, the oxidation of one of the cyclic forms of D-glucose can readily be seen to give a formate ester (as well as a C-formyl group) on the atom originally denoted as C5. It... 

Kinetics of oxidation of four pentoses by bromamide-T were conducted in alkaline medium at different temperatures and the overall activation parameters have been calculated.52 Aldonic acids were the oxidation products, and a mechanism was suggested in which formation of the enediol anion of the sugar is the rate-limiting step. As aldoses may undergo epimerization in alkaline solutions, the oxidation of monosaccharides with bromamide-T was also performed in hydrochloric acid solution.53 Kinetic parameters revealed a low reactivity of ketoses relative to aldoses, and indicated that the cyclic forms of the latter are involved in the oxidations. 

The reaction probably proceeds via the cyclic forms of the sugars and lactones, as equilibria between the various cyclic forms and the acyclic form are presumably established rapidly under the strongly acidic conditions of these oxidations. Thus, D-galactose undergoes oxidation to (acyclic) galactaric acid, whereas similar reaction of D-mannose affords a dilactone (see preceding Chapter). 

A sugar (such as glucosamine) in which a hydroxyl group is replaced by an amino group, (p. 1139) The hemiacetal carbon in the cyclic form of a sugar (the carbonyl carbon in the open-chain form). The anomeric carbon is easily identified because it is the only carbon with two bonds to oxygen atoms, (p. 1112)... 

These are mixed acetals resulting from the replacement of the hydrogen atom on the anomeric (gly-cosidic) OH of the cyclic form of a sugar by a radical R derived from an alcohol or phenol (ROH). They are named by changing the terminal -e of the name of the corresponding cyclic form of the saccharide to -ide the name of the R radical is put at the front of the name followed by a space. 

These flat, six-membered rings used to represent the cyclic hemiacetals of glucose and other sugars are called Haworth projections. The cyclic forms of glucose now have five steret enic centers, the four from the startii hydroxy aldehyde and the new anomeric carbon. a-D-Glucose and P-D-glucose are diastereomers, because only the anomeric carbon has a different configuration. 

SCHEME 6.23 The regiochemistry of the DAST fluorination can be controlled through protecting groups, anomeric configuration and the cyclic form of the sugar. 

There is an anomeric carbon, resulting from the equilibrium between the acychc form and the four cyclic forms of a sugar monomer in solution. These cychc forms are comprised of a five-membered furanose ring and the generally more abundant six-membered pyranose ring. Mutorotation around the anomeric centre converts the a-form into the P-form. 

In search for the key intermediates to meat flavor development in heated cysteine-sugar systems, it was found that in addition to thiazolidine derivatives also the tetrahydro-l,4-thiazine derivatives are being formed. These tetrahydro-l,4-thiazines, which are the cyclic form of Amadori compounds of cysteine, have excellent meat flavor precursor properties and are likely to play a prominent part in meat flavor development. Another major pathway to meat flavor development is the reaction of cysteine with the Amadori compounds of other amino acids. Model experiments showed that both pathways are probably of about equal importance for flavor development in boiled meat and process flavorings, this in spite of the low reactivity of cysteine with sugars. It seems that the first pathway is general-acid-catalyzed by the other amino acids, whereas the second pathway is inhibited by cysteine. 

This discussion will deal with some aspects of the interconversion of the cyclic forms of a carbohydrate to their acyclic forms and to each other. Since a topic of this nature cannot be well covered in a single Chapter, the discussions will be limited to the consideration of a cross-section of closely related reactions which include the formation and hydrolysis of aldono-lactones and aldosides and the deamination of amino sugars. 

---