Glucose enolization

M.p. 190-192 C. The enolic form of 3-oxo-L-gulofuranolactone. It can be prepared by synthesis from glucose, or extracted from plant sources such as rose hips, blackcurrants or citrus fruits. Easily oxidized. It is essential for the formation of collagen and intercellular material, bone and teeth, and for the healing of wounds. It is used in the treatment of scurvy. Man is one of the few mammals unable to manufacture ascorbic acid in his liver. Used as a photographic developing agent in alkaline solution. 

Carbohydrates undergo a number of isomerization and degradation reactions under both laboratory and physiological conditions. For example, a mixture of glucose, fructose, and mannose results when any one of them is treated with aqueous base. This reaction can be understood by examining the consequences of enolization of glucose ... 

Because the configuration at C-2 is lost on enolization, the enediol intermediate can revert either to D-glucose or to D-mannose. Two stereoisomers that have multiple chirality centers but differ in configuration at only one of them are refened to as... 

Glycolysis is a ten-step process that begins with isomerization of glucose from its cyclic hemiacetal form to its open-chain aldehyde form—a reverse nucleophilic addition reaction. The aldehyde then undergoes tautomerixa-tion to yield an enol, which undergoes yet another tautomerization to give the ketone fructose. 

Glucose 6-phosphate is isomerized to fructose 6-phosphate by ring opening followed by a keto-enol tautomerization. 

Following hydrolysis, keto-enol tautomerization of the carbonyl group from C2 to Cl gives glucose 6-phosphate. The isomerization is the reverse of step 2 in glycolysis. 

In another approach, a glucose-derived titanium enolate is used in order to accomplish stereoselective aldol additions. Again the chiral information lies in the metallic portion of the enolate. Thus, the lithiated /m-butyl acetate is transmetalated with chloro(cyclopentadienyl)bis(l,2 5,6-di-0-isopropylidene- -D-glucofuranos-3-0-yl)titanium (see Section I.3.4.2.2.I. and 1.3.4.2.2.2.). The titanium enolate 5 is reacted in situ with aldehydes to provide, after hydrolysis, /i-hydroxy-carboxylic acids with 90 95% ee and the chiral auxiliary reagent can be recovered76. 

The reaction mechanism postulated by Wolfrom, Schuetz and Cavalieri87 for the formation of 5-(hydroxymethyl)-2-furaldehyde from D-glucose involves the enol (XXXV) of 3-deoxy-D-glucosone as an intermediate an alternative pathway proposed by these same workers included the enol... 

Table II indicates those compounds which, on reaction with D-glucose, have not yielded any crystalline product. A large enol content in the ketonic...

Experiments attempting the interaction of D-glucose with ethyl O-pro-pionylacetoacetate have proved fruitless. A positive result for this compound, in which the enolic structure has been fixed by substitution on the oxygen, would have been favorable to theories based on involvement of the enolic form of the ketonic compound. 

Silyl enol ether (38), derived from D-glucose, undergoes a useful one-carbon extension by way of an asymmetric aldol reaction the conditions of the indium(ni) catalysis in water are very convenient. 

Removal of the a-hydrogen in o-glucose leads to enolization (we have omitted the enolate anion in the mechanism). Reversal of this process allows epimerization at C-2, since the enol function is planar, and a proton can be acquired from either face, giving D-mannose as well as o-glucose. Alternatively, we can get isomerization to o-fmctose. This is because the intermediate enol is actually an enediol restoration of the carbonyl function can, therefore, provide either a C-1 carbonyl or a C-2 carbonyl. The equilibrium mixture using dilute aqueous sodium hydroxide at room temperature consists mainly of o-glucose and o-fructose, with smaller amounts of D-mannose. The same mixture would be obtained... 

Glucose 6-phosphate is then isomerized to fructose 6-phosphate. This conversion of an aldose sugar to a ketose sugar is easy to rationalize in terms of keto-enol tautomerism (see Box 10.1). 

We should first consider the open-chain form of glucose 6-phosphate, rather than its pyranose hemiacetal form (see Section 12.2.1). The open-chain aldose has the requirements for enolization, namely a hydrogen a to the aldehyde carbonyl group. Enolization produces in this case an enediol, which can revert to a keto form in two ways, i.e. reforming... 

This is achieved by two keto-enol tautomerism reactions and a common enol (see Box 10.1). Mechanistically, it is identical to the isomerization of glucose 6-phosphate to fructose 6-phosphate seen earlier in the sequence, so we can move on to the next step of the pathway. 

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