Acetoin condensation

In a subsequent report, however, the thiazolopapains were shown to be competent in catalyzing a carbon-carbon bond-forming reaction of the acetoin condensation type (Fig. 14) [50]. The reaction of the papain derivatives with 6-oxo-heptanal was assayed at neutral pH (Fig. 14). The course of the reaction was monitored by HPLC and the products analyzed by H NMR. In the case of the... 

In 1957, Breslow (13) showed that the hydrogen atom in the 2-position of the thiazolium-ion portion of thiamin is ionized readily the electronic structure of the anion imitates that of cyanide ion. The chemistry of thiamin can then be explained the decarboxylation of pyruvate and the acetoin condensation are processes that follow conventional mechanisms in modern language, thiamin allows an acyl group to become an anion equivalent. Subsequent to Breslow s initial discovery, he and McNelis (14) synthesized 3,4-dimethyl-2-acetylthiazolium ion, and showed that in fact it is hydrolyzed rapidly. 

By studying other thiazolium compounds in the catalyzed acetoin condensation, it was found that blocking the 2-position either with a bulky neighboring substituent (isopropyl), or by substitution with a methyl group at this position destroys the catalytic abilities of the thiazolium salt (328 ... 

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. 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

Carboxy-4-methyl-5-pentyl-2-furanpropanoic acid (273), isolated from blood and urine, is a hitherto unknown class of metabolic compound. The structure of (273) has recently been confirmed by synthesis (80CB699). 2,4,5-Trialkyl substituted furan-3-carboxylic acids have been synthesized from acyloin and /3-ketoesters by treatment with zinc chloride. By analogy with this synthetic route, the reaction of acetoin with 3-oxoadipic acid dimethyl ester was found to yield the 2,3-dimethylfuran (274). The dimethyl ester (275) was prepared by condensation of 3-chloro-2-octanone with 3-oxoadipic acid dimethyl ester and was shown to be identical with the dimethyl ester of the natural product. 

Among such genera as Aerobacter and Serratia part of the pyruvate formed is condensed with decarboxylation to form S acetolactate,143 which is decarboxyl-ated to acetoin (Eq. 17-26 pathway g of Fig. 17-9). 

Condensation 9 Acetaldehyde to acetoin. acetaldehyde to pyruvic acid to alpha-acetolactic acid. 

As demonstrated in Scheme 3, the ThDP-bound active aldehyde 6 as an acyl-donor may be added to a second aldehyde cosubstrate (acyl-acceptor) in an acyloin condensation-type reaction. This carboligase reaction was intensively investigated with acetaldehyde as an acyl-donor, which may be either condensed to a further acetaldehyde molecule yielding acetoin [1,26,27,29,63,153,154] or to a wide range of various aliphatic, aromatic and heterocyclic aldehydes [5,14,118,151,154-157,161]. 

Although the utility of transaminases has been widely examined, one such limitation is the fact that the equilibrium constant for the reaction is near unity. Therefore, a shift in this equilibrium is necessary for the reaction to be synthetically useful. A number of approaches to shift the equilibrium can be found in the literature.53 124135 Another method to shift the equilibrium is a modification of that previously described. Aspartate, when used as the amino donor, is converted into oxaloacetate (32) (Scheme 19.21). Because 32 is unstable, it decomposes to pyruvate (33) and thus favors product formation. However, because pyruvate is itself an a-keto acid, it must be removed, or it will serve as a substrate and be transaminated into alanine, which could potentially cause downstream processing problems. This is accomplished by including the alsS gene encoding for the enzyme acetolactate synthase (E.C. 4.1.3.18), which condenses two moles of pyruvate to form (S)-aceto-lactate (34). The (S)-acetolactate undergoes decarboxylation either spontaneously or by the enzyme acetolactate decarboxylase (E.C. 4.1.1.5) to the final by-product, UU-acetoin (35), which is meta-bolically inert. This process, for example, can be used for the production of both l- and d-2-aminobutyrate (36 and 37, respectively) (Scheme 19.21).8132 136 137... 

Another early success in biomimetic chemistry concerns reactions promoted by thiamin. In 1943, more than 35 years ago, Ukai, Tanaka, and Dokowa (12) reported that thiamin will catalyze a benzoin-type condensation of acetaldehyde to yield acetoin. This reaction parallels a similar enzymic reaction where pyruvate is decarboxylated to yield acetoin and acetolactic acid. Although the yields of the nonenzymic process are low, it is clearly a biomimetic process further investigation by Breslow, stimulated by the early discovery of Ugai et al., led to an understanding of the mechanism of action of thiamin as a coenzyme. 

The newest enzyme for use in beer is acetolactate decarboxylase, used to decrease the fermentation time, by avoiding the formation of diacetyl. Externally or internally produced a-acetolactate decarboxylase transforms the a-acetolactate to acetoin (acetylmethylcarbinol) without the enzyme, acetolactate goes to diacetyl, and then a secondary fermentation slowly reduces it to acetoin. Avoiding or reducing the secondary fermentation results in significant reduction in storage capacity and money tied up in inventory Q). Normally acetolactate forms by the thiaminepyrophosphate-catalyzed acyloin condensation of acetaldehyde and pyruvic acid (2) or by the condensation of two pyruvic acid molecules to yield acetolactate and CC. Acetolactate is important in the synthesis of isoleucine and valine by the yeast. The acetolactate left at the end of the primary fermentation is oxidized spontaneously in a nonenzymatic reaction to diacetvl and C0.> (Eqn. 1)... 

The identity of the enzyme(s) involved in the latter reaction has been debated (13). However, the formation of the above hydro-xyketone, in analogy with acetoin, has been conceptualized as the consequence of the condensation of the "active" form of acetaldehyde, that is formed by decarboxylative addition of pyruvate to thiamine pyrophospate, with benzaldehyde.The role of pyruvate, in fact has been established. The same mechanism can be invoked for the reaction of cinnamaldehyde.lt is known that the pyruvate decarboxylase (E.C. 4.1.1.1) accepts as substrates a-oxoacids... 

In the second classical method (Bischler synthesis), an aromatic primary or secondary (arylalkyl, but not diaryl) amine is condensed with an obromo (or better, hydroxy) ketone to give a 2,3-dialkylindole. This in turn is alkylated directly to the 1,2,3,3-tetraalkylindoleninium salt. Use of acetoin gives 2,3-dimethylindole, which is easily isolated and purified. The Bischler synthesis from a substitued aniline, and especially from anilines bearing one or more alkoxy groups, is much preferred in practice for indoles substitued in the 4-7-positions, since the substituted aiylhy-drazines needed for the Fischer synthesis are costly, unstable, or unavailable. 

Disposition in the Body. Acetaldehyde is a major intermediate metabolite of ethanol and is also a metabolite of metaldehyde, paraldehyde, and phenacetin. It undergoes further metabolism by oxidation to acetic acid and, eventually, to carbon dioxide and water. A minor pathway involves condensation with pyruvic acid to form acetoin. 

Diacetyl, acetoin and 2,3-butanediol These compounds are produced by condensing of pyruvate with ethanal. This reaction produces acetolactate which is later decarboxylated. Diacetyl is produced if the decarboxylation is oxidative, whereas acetoin is produced if the decarboxylation is not oxidative. Acetoin can also be formed by directly reducing diacetyl. Finally, acetoin can be reduced to form 2,3-butanediol. This last reaction is reversible (Ribereau-Gayon et al. 2000c). Acetoin and especially diacetyl give off a buttery smell that may... 

The nonitol group in nonitolcaldarchaeol is found only in the Sulfolobales, including the genera Desulfurolobus, Acidianus and Metallosphaera[ Q,2Qi. Whole-cell studies showed that the biosynthesis of nonitol in S. solfataricus [2Q,9%] could occur by an aldol- or acetoin-type condensation between a triose and a hexose precursor, followed... 

Pyruvate decarboxylase catalyzes the nonoxidative decarboxylation of pyruvate to acetaldehyde and carbon dioxide. When an aldehyde is present with pyruvate, the enzyme promotes an acyloin condensation reaction. The mechanistic reason for this fortuitous reaction is well understood and involves the aldehyde outcompeting a proton for bond formation with a reactive thiamine pyrophosphate-bound intermediate (90,91). When acetaldehyde is present, the product formed is acetoin. Benzalde-hyde results in the production of phenylacetylcarbinol (Fig. 26). Both of these condensations are enantioselective, forming the R enantiomer preferentially in both cases. 

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