A-Keto acids deriv

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. 

Other components described in the literature which are able to enhance saltiness or umami taste are umami-tasting glutamate glycoconjugates (e.g. 18 or 19) [42], (S)-malic acid 1-0-D-glucopyranoside (morelid 20) [43], theogalline (21) [44], M-lactoyl ethanolamine (22) [45] and JV-gluconyl ethanolamines (23) [46], a-keto acids derived from amino acids (e.g. 24) [47] and some N-succinoyl derivatives of aspartic acid or glutamic acid (e.g. 25 and 26) [48]. 

The stereoselective reduction of a-keto acid derivatives at a preparative scale is performed with cinchona-modified Pt catalyst (see Chapter 18). Enantioselectivities range from 57-95% for the reduction of a-keto acid derivatives5 and is dependent on the preparation of the Pt catalyst.5 22 205 206... 

Bophoz (32) is a combination of a phosphine and an aminophosphine and is prepared in 4 steps from ppfa with high overall yields.24 The ligand is air-stable and effective for the hydrogenation of enamides, itaconates, and a-keto acid derivatives (Table 15.7). As observed for several ligands... 

FIGURE 18.3 a-Keto acid derivatives listed in Table 18.1. 

The procedure given here is a simple and efficient method for producing 1,3-dithiane, a valuable intermediate in the synthesis via lithio derivatives of a wide variety of compounds, including aldehydes, ketones, a-hydroxyketones, 1,2-diketones, and a-keto acid derivatives.2... 

The presence of two substituents (generally both at the /3-carbon) still allows the reaction to occur in good yields [25,26], and the same is true when three substituents are present. Thus Verlhac et al. described the alkylation of stannylated silyl enol ethers and, after workup, obtained aryl ketones in moderate to good yields (Scheme 4-4) [27], Booth et al. [28] (Scheme 4-5) and Casson and Kocienski [29] reported couplings of heterofunctionalized vinyltins, Takeda et al. [30] prepared a series of highly substituted ajS-unsaturated ketones (Scheme 4-6) and Shi et al. [31] a number of /3-fluoro-a-keto acid derivatives. 

Problem 29.16 i From what amino acid is the following a-keto acid derived ... 

Three structural elements in the cinchona molecule were identified to affect rate and ee of the enantioselective hydrogenation of a-keto acid derivatives (i) an extended aromatic moiety, (ii) the substitution pattern of the quinuclidine (the absolute configuration at C8 controls the sense of induction N-alkylation yields racemate), and (iii) the substituents at C9 (OH or MeO is optimal larger groups reduce the enantioselectivity). 

A pictorial overview of the substrate scope is presented in Figure 2.3. More detailed results for synthetically useful reactions are presented in the next sections. Besides a-keto acid derivatives, a-keto acetals, a-keto ethers, and some trifluoromethyl ketones have been shown to give high ee values with Pt-based catalysts. Pd-based catalysts give moderate enantioselectivities for most a,P-unsaturated acids and up to 94% ee for selected pyrones. Nevertheless, for the synthetic chemist, the substrate scope is still relatively narrow, and it is not expected that new important substrate classes will be found soon. On the other hand, the chemoselectivity of this system has not yet been exploited to its full value, and this might hold a potential for synthetically useful applications in the future. 

Figure 2.3 (a) Structures of good, medium, and bad substrates for cinchona-modified catalysts, (b) Structures of suitable a-keto acid derivatives. 

Shi, G.-Q., and Cao, Z.-Y, Ethyl 2-benzyloxy-3.3-difluoropropenoate as a novel synthon of P-fluoro-a-keto acid derivatives. Preparation and reactions with nucleophiles, J. Chem. Soc., Chem. Commun.. 1969, 1995. 

Hydrogenation / allylic alcohol, tetrasub-stituted C=C, enamine a-Keto acid derivatives, 2 3 3 2 10... 

Keywords. 3-Functionalized ketones, a-Keto acid derivatives. Cinchona modified Pt catalysts. Chiral imprints. Chiral metal surfaces. Chiral polymers. Cyanohydrin formation. Cyclic Dipeptides, Epoxidation catalysts. Heterogeneous catalysts. Hydrogenation catalysts. Modified metal oxides. Polypeptides, Tartrate-modified Nickel catalysts... 

In maple syrup urine disease, also called branched chain ketoaciduria, the a-keto acids derived from leucine, isoleucine, and valine accumulate in large quantities in blood. Their presence in urine imparts a characteristic odor that gives the malady its name. All three a-keto acids accumulate because of a deficient branched chain a-keto acid dehydrogenase complex. (This enzymatic activity is responsible for the conversion of the a-keto acids to their acyl-CoA derivatives.) If left untreated, affected individuals experience vomiting, convulsions, severe brain damage, and mental retardation. They often die before 1 year of age. As with phenylketonuria, treatment consists of rigid dietary control. 

Reductive animation of a-keto acid derivatives gives rise to optically active amino acids if chiral amines are used1 7. In the synthesis of natural (S)-alanine (R = CH3) an ee of 67 % is obtained by using (S)-a-methylbenzylamine as the chiral amine118-120. 

Amino acid tert-butyl esters can be used as chiral amines in the reductive amination of a-keto acid derivatives. Thus, alanine was prepared from methylpyruvate with 60% ee127. Analogous optical yields are obtained by the reduction and subsequent hydrolysis of the iminolactams formed by the reaction of an a-keto ester and slilbenediaminel2S. 

However, the asymmetric reductive animation of a-keto acids and a-keto acid derivatives is of very limited practical importance. Many alternative methods 134 are used in industry and other laboratories in order to produce optically active a-amino acids. 

In this disease, the a-keto derivatives for all three branched-chain amino acids are found in the urine. The transamination of the amino acids is normal, but the enzyme related to the oxidation of the a-keto acid derivatives (branched-chain a-keto acid dehydrogenase) is genetically defective or missing. Thus, there is an accumulation of the branched-chain amino acids and keto... 

The term sialic acid (Sia) refers to a group of nine-carbon a-keto acids derived from Neu5Ac, 5-glycolylneur-aminic acid (Neu5Gc), and deaminated neuraminic acid (KDN) (Figure 20). A closely related keto-deoxy acid,... 

Carbonyl reduction. Many substrates have been reduced enantioselectively to give alcohols trifluoromethyl ketones, a-acetoxyketones, pyridinophenones, ethyl a-methylacetoacetate, a-keto acid derivatives," and 3-chloro-2-oxoaIkanoic esters a,/3-Epoxy ketones undergo reduction and hydrolytic ring opening/... 

Double carbonylation of aryl halides to a-keto acid derivatives... 

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