Enediol Enediolate

Enolization of an aldose or a ketose gives an enediol Enediols can revert to aldoses or ketoses with loss of stereochemical integrity at the a carbon atom... 

The energies of the enediolate/enediol intermediates relative to the bound DHAP/ G3P have not been evaluated experimentally they do not accumulate sufficiently to allow spectroscopic detection. However, the proposals put forth by Albery and Knowles regarding the evolution of catalytic efficiency are based, in part, on the assumption that the various bound species, substrate, intermediates, and products, are isoenergetic on the reaction coordinate ( differential binding to achieve a reduction in A Go) and that the transition states for the proton transfer reactions can be selectively stabilized ( catalysis of elementary steps to achieve a reduction in AG int) [7]. Without a measure of the stabilities of the enediol/enediolate intermediates relative to DHAP and G3P, the importance of reductions in AGo and/or AG int cannot be dissected. 

The different conclusions regarding the energies of the intermediates have an additional implication for the Knowles and Albery hypotheses, i.e., assessing the importance of catalysis of elementary steps to achieve a reduction in AG int- If the enediol/enediolate intermediates are approximately isoenergetic with DHAP and G3P, as predicted by Karplus, the value of AG int is not significantly reduced from the value (- 12 kcal mol ) found in nonenzymatic reactions. However, if the intermediates are significantly more unstable than DHAP and G3P, the value of AG int must be decreased to account for the observed rates of proton abstraction from DHAP and G3P. 

The formation of acyloins (a-hydroxyketones of the general formula RCH(OH)COR, where R is an aliphatic residue) proceeds best by reaction between finely-divided sodium (2 atoms) and esters of aliphatic acids (1 mol) in anhydrous ether or in anhydrous benzene with exclusion of oxygen salts of enediols are produced, which are converted by hydrolysis into acyloins. The yield of acetoin from ethyl acetate is low (ca. 23 per cent, in ether) owing to the accompanying acetoacetic ester condensation the latter reaction is favoured when the ester is used as the solvent. Ethyl propionate and ethyl ji-butyrate give yields of 52 per cent, of propionoin and 72 per cent, of butyroin respectively in ether. 

The mechanism of the formation of an acyloin from an ester may involve the initial formation of a diketone the latter is reduced by the metal to give the sodium salt of the enediol form of the acyloin ... 

Aldoses are reducing sugars because they possess an aldehyde function m then-open chain form Ketoses are also reducing sugars Under the conditions of the test ketoses equilibrate with aldoses by way of enediol intermediates and the aldoses are oxidized by the reagent... 

Because Ihe configuralion al C 2 is losl on enolizalion Ihe enediol mlermediale can reverl eilher lo d glucose or lo d mannose Two slereoisomers lhal have mulliple chiralily cenlers bul differ m configuralion al only one of Ihem are referred lo as... 

There is another reaction available to the enediol intermediate Proton transfer from water to C 1 converts the enediol not to an aldose but to the ketose d fructose... 

Physical Properties. Table 3 contains a summary of the physical properties of L-ascorbic acid. Properties relating to the stmcture of vitamin C have been reviewed and summarized (32). Stabilization of the molecule is a consequence of delocalization of the TT-electrons over the conjugated enediol system. The highly acidic nature of the H-atom on C-3 has been confirmed by neutron diffraction studies (23). 

When this isomeiization reaction is catalyzed by alkah, it is termed the Lobry de Bmyn-Alberda van Ekenstein reaction. By it, D-glucose, D-mannose, and D-fmctose can be interconverted. The isomerizations involve a common intermediate, the 1,2-enediol. In the Glu—Man—Fm interconversions... 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

The chemical reaction catalyzed by triosephosphate isomerase (TIM) was the first application of the QM-MM method in CHARMM to the smdy of enzyme catalysis [26]. The study calculated an energy pathway for the reaction in the enzyme and decomposed the energetics into specific contributions from each of the residues of the enzyme. TIM catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) as part of the glycolytic pathway. Extensive experimental studies have been performed on TIM, and it has been proposed that Glu-165 acts as a base for deprotonation of DHAP and that His-95 acts as an acid to protonate the carbonyl oxygen of DHAP, forming an enediolate (see Fig. 3) [58]. 

The results supported the proposal of Glu-165 as the general base and suggested the novel possibility of neutral histidine acting as an acid, contrary to the expectation that His-95 was protonated [26,58]. The conclusion that the catalytic His-95 is neutral has been confinned by NMR spectroscopy [60]. The selection of neutral imidazole as the general acid catalyst has been discussed in terms of achieving a pX, balance with the weakly acidic intermediate. This avoids the thermodynamic trap that would result from a too stable enediol intermediate, produced by reaction with the more acidic imidazolium [58]. 

Lys-12, which lies close to the active site, and the role of this residue is the stabilization of the enediolate. This explicitly explains the inactivity of a Lys-12 to Met mutation [61]. 

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... 

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