Aldols mechanisms

Step 2 of Figure 29.13 Decarboxylation and Phosphorylation Decarboxylation of oxaloacetate, a jB-keto acid, occurs by the typical retro-aldol mechanism like that in step 3 in the citric acid cycle (Figure 29.12), and phosphorylation of the resultant pyruvate enolate ion by GTP occurs concurrently to give phosphoenol-pyruvate. The reaction is catalyzed by phosphoenolpyruvate carboxykinase. 

The usefulness of FGI operations is easily understood considering a very simple example. 1,3-Butanediol, notwithstanding being a 1,3-C system, does not offer a reasonable disconnection mechanism. However, if the primary hydroxyl group is converted to a carbonyl group, the resulting product can be then disconnected into two stable identical molecules of acetaldehyde, according to a reasonable retro-aldol mechanism, and the whole process represents a simple solution in accordance with the criterium of maximum simplicity. 

Cleavage of a sugar at the C-2-C-3 bond by the reverse-aldol mechanism results in the glycolaldehyde ion (79). As glycolaldehyde cannot react by a /3-elimination mechanism similar to that of glyc-eraldehyde, it undergoes aldol addition with itself, or with other... 

Self-addition of fragments occurs by the familiar, base-catalyzed, aldol mechanism. This reaction shows general, base catalysis,139-140 indicating that the rate-controlling step is the formation of the anion (80). As it is this anion that is liberated in the cleavage process of the... 

Gibberellins which have a saturated ring A undergo epimerization at C-2 with dilute alkali at room temperature, presumably by a reversed aldol mechanism via intermediate (XXXIII) as first suggested by J. W. Comforth (3a). This epimerization has been shown to occur with gibberellin At and its methyl ester (XXXIV), with both C-8 epimeric tetrahydro derivatives of gibberellic acid and... 

Figure 4. Froposed retro-aldol mechanism for the base-catalyzed epimerization...

The experimental atomic ratio of deuterium to hydrogen of 0.106 corresponds closely to the ratio calculated for the aldol mechanism (0.091) on the supposition that deuterium and hydrogen atoms in the alpha position participate equally in the condensation. 

The estimated C-D content of the ketone produced from l-octanol-2-d is consistent with the proposed aldol mechanism. 

In view of the indicated absence of any marked hydrogen-deuterium exchange under ketone-synthesis conditions, the presence of substantially the theoretical atomic ratio of deuterium to hydrogen in the gaseous product provides additional support for the proposed aldol mechanism. 

One possible mechanism for the degradation of 2,4-decadienal is the retro-aldol mechanism proposed by Josephson and Lindsay (8) for the oxidation of a,B-unsaturated fatty aldehydes. In their investigation of the degradation products of 2,4-decadienal, Josephson and Lindsay (9) identified 2-octenal and hexanal as primary products. Both 2-octenal and hexanal were identified in the present systems. 

The symmetry of the aldol mechanism would then allow for catalysis of the hydrolysis of the resulting hydroxyimminium compound to the aldol. 

Figure 6.2 Reverse aldol-aldol mechanism for the Bilik and related reactions. In complex II, if the carbonyl group comes loose and rotates about C3-C4, the products will be epimerised at C3.

The enzyme 2-C-methyl-D-erythritol-4-phosphate synthetase appears to catalyse a Bilik reaction (Figure 6.10) the substrate l-deoxyxylulose-5-phosphate is converted to the title compound via an intermediate aldehyde, whose carbonyl derives from C3 of the substrate. The first step is thus a Bilik reaction and the aldehyde is subsequently reduced by the enzyme using NADPH as reductant, The X-ray crystal structure of the Escherichia coli enzyme in complex with the promising antimalarial Fosmidomycin (a hydroxamic acid) reveals a bound Mn " coordinated to oxygens equivalent to the substrate carbonyl and 03. The stereochemistry and regiochemistry follow the normal Bilik course, although the crystallographers favour an alkyl shift rather than a reverse aldol-aldol mechanism. The intermediate aldehyde has been shown to be a catalytically competent intermediate. 

Reaction catalysed by 2-C-methyl-D-erythritol-4-phosphate synthetase. The reaction is drawn with a metal-templated reverse aldol-aldol mechanism, rather than the alkyl shift mechanism. The prop-2-en-2,3-diolate is below the plane of the glycolaldehyde phosphate. 

An enzymic counterpart of these complex base-catalysed rearrangements of sugars may be the reaction catalysed by 4-phospho-3,4-dihydroxy-2-butanone synthetase. The enzyme catalyses the formation of the eponymous intermediate in secondary metabolism from ribulose 5-phosphate. Labelling studies indicated that C1-C3 of the substrate became C1-C3 of the product, that H3 of the substrate derived from solvent and that C4 was lost as formate. X-ray crystal structures of the native enzyme and a partly active mutant in complex with the substrate are available. The active site of the enzyme from Met ha-nococcus jannaschii contains two metals, which can be any divalent cations of the approximate radius of Mg " or Mn ", the two usually observed. Their disposition is very reminiscent of those in the hydride transfer aldose-ketose isomerases, but also to ribulose-5-phosphate carboxylase, which works by an enolisation mechanism, so the enolisation route suggested by Steinbacher et al. is repeated in Figure 6.14, as is the Bilik-type alkyl group shift, for which an equivalent reverse aldol-aldol mechanism cannot be written. 

Only the aldol mechanism is shown not the subsequent dehydration. 

Controlled conditions are required for the production of simple adducts, for under more vigorous alkaline treatment, ring opening, then carbon-carbon bond cleavage via a retro-aldol mechanism takes place, and such processes, which are essentially the reverse of a route used for the synthesis of 1-benzopyryliums... 

Interestingly, when boron triiluoride etherate was used as catalyst, 9 reversal of C-5,6 stereochemistry was observed, affording primarily tram compounds. It was postulated that these reactions involve an aldol-likfl mechanism [Eq. (12)] that is trans (threo) selective. Combinations of the pericyclic and aldol mechanisms are probably operative in some cases. 

Besides the cleavage of C-T/C-2 bond of the substrate, the DHNA of E. coli can also catalyze the epimerization of the 1 position of dihydroneopterin. That reaction is believed to proceed through bond cleavage followed by religation, that is, a retroaldol/aldol mechanism. ... 

Normally, silyl enol ethers are considered to react with aldol substrates via an aldol mechanism, but Mikami and coworkers, in their examples, showed that the reaction involves an ene mechanism. This is clear from the regiochemistry of the product (7.186) that is isolated from the reaction of silyl enol ether (7.184) and aldehyde (7.185) before hydrolysis. The same catalyst system has been used for the asymmetric desymmetrisation of the diene (7.187) with aldehyde (7.183). The ... 

The cascade synthesis of tetrahydrofuran-containing oxacyclic molecules takes place by a 2-oxonia[3,3]-sigmatropic-aldol mechanism rather than by a Prins cyclization-pinacol rearrangement sequence (Scheme 6). ... 

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