Aldoses deprotonation

In addition to serving as structural motifs, enols and enolates are involved in diverse biological processes. Several enol/enolate intermediates have been proposed to be involved in glycolysis (Section IV.A), wherein c/ -enediol 21 is proposed to be an intermediate in the catalytic mechanism of phosphohexose isomerase and an enol-containing enamine intermediate (22) has been proposed in the catalytic pathway of class I aldolase. In the case of glucose-fructose (aldose-ketose) isomerization, removal of the proton on Cl-OH produces the aldose while deprotonation of C2-OH yields the ketose, which is accompanied by protonation at the C2 and Cl positions, respectively. There are several cofactors that are involved in various biological reactions, such as NAD(H)/NADP(H) in redox reaction and coenzyme A in group transfer reactions. Pyridoxal phosphate (PLP, 23) is a widely distributed enzyme cofactor involved in the formation of a-keto acids, L/D-amino... 

One mechanism proposed earlier was the formation of metal-bound enolate intermediate via deprotonation at C3 position. However, a recent study failed to detect a significant deuterium primary kinetic isotope effect which excludes this pathway and suggested an aldolase cleavage mechanism where deprotonation of the substrate (115) is followed by bond cleavage (116), analogous to the reversed reaction in aldose mechanism (114 113) discussed above. Cleavage is followed by reposition of the fragments (117) and aldol condensation (118) to complete the epimerization. 

By virtue of the aldehyde at the reducing end, sugars are susceptible to deprotonation and isomerization. The rearrangement from an aldose sugar to a ketose sugar, shown in Scheme 6.80, is a direct result of this property [123]. Based on the initial enolization step, this chemistry is easily applied to the direct C-2 epimerization of 2-deoxy-2-aminosugars. Scheme 6.81 illustrates this reaction in the conversion of A-acetyl-D-glucosamine to A-acetyl-D-mannosamine [124,125]. 

The reaction begins with the formation of a Schiff base between a lysine residue in transaldolase and the ketose substrate. Protonation of the Schiff base (2) leads to the release of the aldose product (3), leaving a three-carbon fragment attached to the lysine residue, (4) This intermediate adds to the aldose substrate, with a concomitant protonation to form a new carbon-carbon bond. Subsequent deprotonation (S) and hydrolysis of the Schiff base (6) release the ketose product from the lysine side chain, completing the reaction cycle. 

The former base-catalyzed aldose-ketose isomerization is named the Lobry de Bruyn-van Ekenstein transformation (Scheme 6.25). Deprotonation of the a-carbonyl carbon of aldose (glucose) requires a base, and results in the form of a series of enolate intermediates. Solid bases such as cation-exchanged zeolites and Mg-Al HT catalyze glucose isomerization in water [176-178]. 

---