A Keto acids, decarboxylation

Thiamine diphosphate (TDP) is an essential coenzyme in carbohydrate metabolism. TDP-dependent enzymes catalyze carbon-carbon bond-breaking and -forming reactions such as a-keto acid decarboxylations (oxidative and non-oxidative) and condensations, as well as ketol transfers (trans- and phospho-ketolation). Some of these processes are illustrated in Fig. 12. 

A vast number of carbonyl compoimds could be formed by a-keto acids decarboxylation. Nevertheless, as they are reduced by yeasts and/ or by the presence of SO2, they exist in wines at levels which are not easily detectable. The compounds susceptible of influencing wine aroma are basically acetaldehyde, 3-hydroxy-2-butanone (acetoin) and 2,3-butanedione (diacetyl) (Bayonove et al, 1998). 

The mechanism for the a-keto acid formation was proposed as shown in Scheme 4, which is reminiscent of those for a-keto amide and ester formation.Benzoyl(hydroxy-carbonyOpalladium complex was assumed as a key intermediate, which undergoes reductive elimination to form a-keto acid. Decarboxylation of this intermediate giving a benzoylpalladium hydride species followed by reductive elimination was proposed to give benzaldehyde as by-product. 

Allows umpolung anion formation by aldehyde carbonyl groups facilitates a-keto acid decarboxylations... 

The sequence begins with a Claisen condensation of ethyl pentanoate to give a p keto ester The ester is hydrolyzed and the resulting p keto acid decarboxylates to yield the desired ketone... 

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

Oxidation of ecgonine (2) by means of chromium trioxide was found to afford a keto acid (3). This was formulated as shown based on the fact that the compound undergoes ready themnal decarboxylation to tropinone (4)The latter had been obtained earlier from degradative studies in connection with the structural determination of atropine (5) and its structure established independently. Confirmation for the structure came from the finding that carbonation of the enolate of tropinone does in fact lead back to ecgonine. Reduction, esterification with methanol followed by benzoylation then affords cocaine. 

Step 2 of Figure 29.11 Decarboxylation The TPP addition product, which contains an iminium ion j8 to a carboxylate anion, undergoes decarboxylation in much the same way that a jB-keto acid decarboxylates in the acetoacetic ester synthesis (Section 22.7). The C=N+ bond of the pyruvate addition product acts... 

Decarboxylation (Section 22.7) The loss of carbon dioxide from a molecule. /3-Keto acids decarboxylate readily on heating. 

TPP-dependent enzymes are involved in oxidative decarboxylation of a-keto acids, making them available for energy metabolism. Transketolase is involved in the formation of NADPH and pentose in the pentose phosphate pathway. This reaction is important for several other synthetic pathways. It is furthermore assumed that the above-mentioned enzymes are involved in the function of neurotransmitters and nerve conduction, though the exact mechanisms remain unclear. 

NAD and NADP and FMN and FAD, respectively. Pantothenic acid is a component of the acyl group carrier coenzyme A. As its pyrophosphate, thiamin participates in decarboxylation of a-keto acids and folic acid and cobamide coenzymes function in one-carbon metabolism. 

Mutation of the dihydrolipoate reductase component impairs decarboxylation of branched-chain a-keto acids, of pyruvate, and of a-ketoglutarate. In intermittent branched-chain ketonuria, the a-keto acid decarboxylase retains some activity, and symptoms occur later in life. The impaired enzyme in isovaleric acidemia is isovaleryl-CoA dehydrogenase (reaction 3, Figure 30-19). Vomiting, acidosis, and coma follow ingestion of excess protein. Accumulated... 

Transketolase (TKase) [EC 2.2.1.1] essentially catalyzes the transfer of C-2 unit from D-xylulose-5-phosphate to ribose-5-phosphate to give D-sedoheptulose-7-phosphate, via a thiazolium intermediate as shown in Fig. 16. An important discovery was that hydroxypyruvate works as the donor substrate and the reaction proceeds irreversibly via a loss of carbon dioxide (Fig. 17). In this chapter, we put emphasis on the synthesis with hydroxypyruvate, as it is the typical TPP-mediated decarboxylation reaction of a-keto acid. ... 

Pyruvic acid is the simplest homologue of the a-keto acid, whose established procedures for synthesis are the dehydrative decarboxylation of tartaric acid and the hydrolysis of acetyl cyanide. On the other hand, vapor-phase contact oxidation of alkyl lactates to corresponding alkyl pyruvates using V2C - and MoOa-baseds mixed oxide catalysts has also been known [1-4]. Recently we found that pyruvic acid is obtained directly from a vapor-phase oxidative-dehydrogenation of lactic acid over iron phosphate catalysts with a P/Fe atomic ratio of 1.2 at a temperature around 230°C [5]. 

Summarizing the results obtained by controlled potential electrolysis and polarography, the reaction process for the electrolytic evolution of CO2 was estimated to be as follows the first step was one electron transfer from DMFC in NB to FMN in W as in Eq. (7). The second step was the catalytic reduction of O2 by FMNH as in Eq. (8). The final step was the oxidation of pyruvic acid by the reduction product of O2, H2O2, in W as in Eq. (9), well-known as an oxidative decarboxylation of a-keto acids [43] ... 

A-Unsubstituted isoxazolidines such as 65 undergo facile decarboxylative peptide couplings with a-keto acids <06JA1452>. The use of water as solvent or cosolvent was particularly beneficial for the formation of amides in high yields. The methyl a-keto esters obtained could be saponified to the corresponding a-keto acids, and the (i-peptide chain could then be extended by reaction with another isoxazolidine. 

Peroxidase and laccase enzymes were used to catalyze the decarboxylation of various tetrahydroisoquinoline-1-carboxylic acids to give high yields of the corresponding 3,4-dihydroisoquinolines (204). Compounds such as 125 (Scheme 29) are derived from Pictet-Spengler ring closure via a-keto acid and aryl amine condensation and are of biogenetic importance. The possible relevance of iso-... 

Thiazoles play a prominent role in nature. For example, the thiazolium ring present in vitamin Bi serves as an electron sink and its coenzyme form is important for the decarboxylation of a-keto-acids. Furthermore, thiazoles are useful building blocks in pharmaceutical agents as exemplified by 2-(4-chlorophenyl)thiazole-4-acetic acid, a synthetic anti-inflammatory agent. 

Phenylglycines are important components of the vancomycin/teicoplanin antibiotics, and the conforma-tionally restricted amino acids contribute to the unique architecture and biological function of these clinically important NRPs. 4-Hydroxyphenylglycine is produced from L-tyrosine in a pathway that involves three enzymes. In the key step, a nonheme iron oxidase catalyzes the oxidative decarboxylation of the a-keto acid derivative of L-tyrosine resulting in loss of carbon dioxide and generation of the phenylglycine carbon framework. 

Biochemical reactions include several types of decarboxylation reactions as shown in Eqs. (1)-(5), because the final product of aerobic metabolism is carbon dioxide. Amino acids result in amines, pyruvic acid and other a-keto acids form the corresponding aldehydes and carboxylic acids, depending on the cooperating coenzymes. Malonyl-CoA and its derivatives are decarboxylated to acyl-CoA. -Keto carboxylic acids, and their precursors (for example, the corresponding hydroxy acids) also liberate carbon dioxide under mild reaction conditions. 

The finding that thiamine, and even simple thiazolium ring derivatives, can perform many reactions in the absence of the host apoenzyme has allowed detailed analyses of its chemistry [33, 34]. In 1958 Breslow first proposed a mechanism for thiamine catalysis to this day, this mechanism remains as the generally accepted model [35]. NMR deuterium exchange experiments were enlisted to show that the thiazolium C2-proton of thiamine was exchangeable, suggesting that a carbanion zwitterion could be formed at that center. This nucleophilic carbanion was proposed to interact with sites in the substrates. The thiazolium thus acts as an electron sink to stabilize a carbonyl carbanion generated by deprotonation of an aldehydic carbon or decarboxylation of an a-keto acid. The nucleophilic carbonyl equivalent could then react with other electro-... 

The first designed catalyst where there was some understanding of the relationship between structure and function was oxaldie 1, a 14-residue peptide that folds in solution to form helical bundles [11] (Fig. 12). Oxaldie 1 was designed to catalyze the decarboxylation of oxaloacetate, the a-keto acid of aspartic acid, via a mechanism where a primary amine reacts with the ketone carbonyl group to form a carbinolamine that is decarboxylated to form pyruvate. The reaction is piCj dependent and proceeds faster the lower the piC of the primary amine if the reaction is carried out at a pH that is lower than the piCj, of the reactive amine. The sequence contains five lysine residues that in the folded state form... 

Two sources of acyl radicals have proved to be useful for the homolytic acylation of protonated heteroaromatic bases the oxidation of aldehydes and the oxidative decarboxylation of a-keto acids. The oxidation... 

Acyl radicals have been obtained from a-keto acids by silver-catalyzed decarboxylation with peroxydisulfate. Decarboxylation takes place easily and can be interpreted according to Scheme 10. 

Periodic acid reacts well in aqueous solution. Usually, if the reactant has to be run in organic solvents, lead tetraacetate is used as the reagent. Interestingly, periodic acid will not act on a-keto acids or a-hydroxy acids whereas lead tetraacetate wiU. The corresponding reactions are actually oxidative decarboxylations. 

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