8-ketoacid

Synthesis No control is need because only the ketoacid can enolise and the aldehyde is more electrophilic. TM 89 is formed in 80% yield when the two starting materials are mixed in MeOH with KOH at room temperature tHelv. Chim. Acta. 1931,14, 783). 

In addition to formation from a ketone, the hydra2ones can be obtained from dicarbonyl compounds by a Japp-Klingemann reaction. This is especially useful for P-ketoesters and P-ketoacids, which undergo either deacylation or decarboxylation. 

Ketene Insertions. Ketenes insert into strongly polarized or polarizable single bonds, such as reactive carbon—halogen bonds, giving acid hahdes (7) and into active acid haUdes giving haUdes of p-ketoacids (8) (46). Phosgene [77-44-5] (47) and thiophosgene [463-71-8] (48) also react with ketenes. 

Dimeric aldoketenes and ketoketenes of P-lactone stmcture show a chemical behavior which is not much different to that of diketene. Thus nucleophiles add ia similar fashion to give derivatives of 3-ketoacids which are mono- or dialkylated at C-2 (aldo- and ketoketene dimers, respectively), but the reaction can often be slower than with the parent compound and, ia case of long-chain or bulky substituents, may not proceed at all. Other reactions can proceed differendy than those with diketene. For an overview of important reactions of aldoketene and ketoketene dimers see Reference 122. 

As shown in equation 12, the chemistry of this developer s oxidation and decomposition has been found to be less simple than first envisioned. One oxidation product, tetramethyl succinic acid (18), is not found under normal circumstances. Instead, the products are the a-hydroxyacid (20) and the a-ketoacid (22). When silver bromide is the oxidant, only the two-electron oxidation and hydrolysis occur to give (20). When silver chloride is the oxidant, a four-electron oxidation can occur to give (22). In model experiments the hydroxyacid was not converted to the keto acid. Therefore, it seemed that the two-electron intermediate triketone hydrate (19) in the presence of a stronger oxidant would reduce more silver, possibly involving a species such as (21) as a likely reactive intermediate. This mechanism was verified experimentally, using a controlled, constant electrochemical potential. At potentials like that of silver chloride, four electrons were used at lower potentials only two were used (104). 

The 4,5,6,7-tetrahydro-2,1-benzisoxazole group is the most reported category. The action of hydroxylamine on )3-diketones produced a mixture of 2,1- and 1,2-benzisoxazoles (Scheme 186). Ring opening gave )3-ketoacids which, under subsequent alkali treatment, degraded to diacids (67AHC(8)277). 

The preparation of long-chain fatty acids has been carried out in this way because cleavage of 115 with strong sodium hydroxide gives the ketoacid (116), which is easily reduced by the Wolf-Kishner method to the saturated acid. A similar sequence of reactions can be carried out starting with the cyclopentanone enamine, and this method allows lengthening the chain... 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

The coupling of arenediazonium compounds 1 to 1,3-dicarbonyl substrates 2 (Z = COR) is known as the Japp-Klingemann reaction As suitable substrates, /3-ketoacids (Z = COOH) and /3-ketoesters (Z = COOR) can be employed. As reaction product an arylhydrazone 4 is obtained. 

In addition to /3-diketones, /3-ketoacids and /3-ketoesters, cyanoacetic ester and related compounds are suitable starting materials. The arylhydrazones 4 thus obtained are of great importance as starting materials for the Fischer indole synthesis, as well as for the preparation of other iV-heterocycles. ... 

Figure A8.18 A racemic mixture of a-hydroxyacids (like L, D-lactate) can be transformed via the corresponding a-ketoacid (pyruvate) to the desired L-amino acid (L-alanine) with cofactor recycling.

Enaminosulphoxides 459 have been obtained in the reaction of the carbanion of methyl methylthiomethyl sulphoxide 324 with nitriles. This procedure has been applied for converting nitriles into a-aminoacids 460527 and a-ketoacids 461528 (equation 275). 

The 9,10-phosphonostearic acid in form of its sodium salt shows a good thermal stability and was efficient as an inhibitor in rust protection. The diethyl-phosphonoacetoxystearic acid methyl ester is used as additive in high-pressure lubricants. Rust protection properties are also shown by 9,10-phosphonostearyl alcohol [157]. Trisodium 9,10-phosphonostearate possesses the best surface activity in an 0.2% aqueous solution showing 33 mN/m at 30°C and a pH value of 10.5 [156]. By the addition of dialkyl phosphite to a,p-unsaturated ketones the y-oxophosphonic acids are available [159]. Addition of dialkyl phosphite to y-ketoacids leads to a-hydroxy-y-carboxyphosphonates see Eq. (86) ... 

In nature, aminotransferases participate in a number of metabolic pathways [4[. They catalyze the transfer of an amino group originating from an amino acid donor to a 2-ketoacid acceptor by a simple mechanism. First, an amino group from the donor is transferred to the cofactor pyridoxal phosphate with formation of a 2-keto add and an enzyme-bound pyridoxamine phosphate intermediate. Second, this intermediate transfers the amino group to the 2-keto add acceptor. The readion is reversible, shows ping-pong kinetics, and has been used industrially in the production ofamino acids [69]. It can be driven in one direction by the appropriate choice of conditions (e.g. substrate concentration). Some of the aminotransferases accept simple amines instead of amino acids as amine donors, and highly enantioselective cases have been reported [70]. 

It should be noted that the absence of a proton in the a position in the case of N-Br-aminoisobutyric acid makes unoperative its decomposition to form an a-ketoacid, and the slight increase in the observed reaction rate constant upon increasing the NaOH concentration can be attributed to a secondary decomposition process, probably leading to the formation of an hydrazine (refs. 22 - 24). 

Ketoacid (1) is an Isomer of a compound made In the book (p T 39) and both were needed for the synthesis of potential fungicides, ... 

The transformation of aromatic amino acids to the 2-ketoacids was mediated by morganii, and these subsequently underwent a hemin-dependent chemical transformation with the production of CO (Hino and Tauchi 1987). 

Exceptionally, in Escherichia coli acireductone dioxygenase (enediol dioxygenase) carries out two enzymatic activities that are responsible for the salvage of methionine, but are encoded by the same gene. Whereas one enzyme is dependent on Fe and produces the ketoacid and formate (Figure 3.34a), the other that is nickel-dependent produces the carboxylic acid, formate, and CO (Figure 3.34b) (Dai et al. 1999). 

A number of factors complicate the aerobic metabolism of amino acids—different enzymes may be used even for the same amino acid the enzymes may be inducible or constitutive depending on their function a-ketoacids may be produced by deamination or amines by decarboxylation. 

Active zinc oxide is capable of forming chelate cements with a number of liquid organic chelates. These include the ) -diketones, ketoacids and ketoesters as well as the 2-methoxy phenols (Nielsen, 1963). 

As an alternative to peptidic inhibitors, which display electrostatic interactions with the active site, covalent inhibitors have also been described recently. Such peptides bear a functional group that can react reversibly with the catalytic serine of the protease. These include aldehydes, a-ketoacid derivates, lactams and boronates. 

These reactions presumably involve formation of a magnesium chelate of the keto acid. The (3-ketoacid is liberated when the reaction mixture is acidified during workup. 

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