Keto Acid Derivatives

Szori et al. [29] investigated a series of a-keto ester RCOCOOR and found that bulky R, and to a lower extent R groups, caused a significant decrease in ee values and rate. Similar results were reported for various R with Pt colloids [22], 

For the corresponding a-keto acids, much less work has been carried out a preliminary study revealed somewhat lower ee values and different optimal solvent systems than for the corresponding esters [25]. Keto amides related to 5 also showed significantly lower ee values [28]. 

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The reachons of -keto acid derivatives with tnfluoromethylsulfenyl chlonde give the a-tnfluoromethanesulfenyl substitution products [4 The products can be treated with a dunethyl sulfoxide-water soluhon to form tnfluoromethylthioke-tones or with potassium hydroxide solution to give tnfluoromethylthroacetic acid (equahon 3) (Table 2)... 

Problem 29.16 From what amino arid is the- following rt-keto acid derived ... 

MMketones from Reactions of an Imidazolide with a jS-Keto Acid Derivative... 

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. 

A simple, efficient, one-step synthesis of quinoxaline 1,4-dioxides from the reaction of benzofurazan oxide 179 with activated alkenes such as enamines was named the Beirut reaction in honor of the city of its discovery. Developments up to 1993 were surveyed by Haddadin and Issidorides <1993H(35)1503>, who first demonstrated this reaction. The benzofurazan oxide 179 (Scheme 52) also condenses with 1,3-diketones <1995M1217, 1996JHC1057, 1999CHE459, 2003EJM791, 2005H(65)1589>, /3-keto acid derivatives <1995H(41)2203,... 

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]. 

Trifluorovinylstannane has been successfully employed in the Stille crosscoupling reaction with aryl or vinyl halides in the presence of a palladium catalyst [190, 191] (Scheme 68). Recently, ethyl 3-(tributylstannyl)-2-methoxyacrylate was prepared from ethyl trifluoropyruvate in several steps and used in the Stille reaction for the synthesis of a-fluoro-keto acid derivatives [192] (Scheme 69). 

Chlorovinyl ketones and related compounds also react with active methylene compounds to form pyran-2-ones, via the unsaturated keto acid derivative (61T63). 

ERYTHRO-SELECTIVE REDUCTION OF a-SUBSTITUTED J-KETO ACID DERIVATIVES WITH PhMe2SiH/H+ REAGENTa... 

Resorcinols. Condensation of this diene with the ketal of a fi- keto acid derivative results in a resorcinol with complete regiocontrol. Thus, the TiCl4-catalyzed reaction of 1 with ketal ester 2 results in the resorcinol 3 in 72% yield. However, use of the acid chloride 4 corresponding to 2 in the same reaction results in the isomeric resorcinol, methyl olivetolate (5). The regiocontrol is based on the reactiv ity order acid chloride > ketal > ester. The resorcinol 5 was used in a biomimetic synthesis of the chromene A1 -tetrahydrocannabinol (6), a component of marijuana. 

Ethylhexanol is also metabolized through oxidative pathways. The primary urinary products from 2-ethylhexanol are 2-ethylhexanoic acid and several keto acid derivatives which appear to be products of P-oxidation (Albro and Corbett 1978). 

The ring closure of 1,5-keto-acids and their derivatives is a widely used strategy for the synthesis of 2A-pyran-2-ones <1984CHEC, 1996CHEC-II>. The 1,5-keto acid derivatives are typically formed in situ with concomitant ring closure to form 2//-pyran-2-ones. There are three main approaches to access the prerequisite 1,5-keto acid derivatives, namely (i) reaction of an ester enolate with a 2-acyl vinyl cation equivalent, (ii) the reaction of a ketone enolate... 

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. 

Best ee for Various oc-Keto Acid Derivatives (For Substrate Structures see Figure 18.3)... 

Generation of a 4-carbon p-keto acid derivative, bound to the pantothenate of the ACP protein... 

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... 

Herbivore diets usually contain adequate amounts of protein as evidenced by the net growth of the animal but the mixture of amino acids derived from vegetation is probably different from that required by the animal Thus herbivores probably synthesize a large proportion of their required amino acids by transamination of keto->acids derived from the carbohydrate part of their diet As a result one would expect that the carbon isotopes of both apatite and gelatin in herbivores would show a direct relationship to the mixture of Co and plants consumed ... 

Monoalkyl acetyl halides, RCHjCOX, are converted to aldoketene dimers. These materials are useful in the synthesis of /3-keto acid derivatives. ... 

The decarboxylation of branched chain keto acids is apparently carried out by the same decarboxylase (EC 4.1.1.1, Mg and thiamine pyrophosphate dependent) which is active on pyruvate in yeast (154, 167) and orange juice (168, 169). The latter enzyme acts on the keto acids derived from valine and isoleucine at about 15% of the pyruvate rate (169). Its activity declines rapidly (80% in 1 hour) in juice (pH 3.4). The malty flavor defect produced by S. lactis var. maltigenes, however, appears to be caused by a specific decarboxylase activity not found in other strains (158, 160) since simultaneous decarboxylation of pyruvate and a-ketoisocaproate was almost additive (163) while a-ketoisocaproate and a-ketoisovalerate competed with each other. Decarboxylation of... 

Stereoselective reduction of a-alkyl-3-keto acid derivatives represents an attractive alternative to stereoselective aldol condensation. Complementary methods for pr uction of either diastereoisomer of a-alkyl-3-hydroxy amides from the corresponding a-alkyl-3-keto amides (53) have been developed. Zinc borohydride in ether at -78 C gave the syn isomer (54) with excellent selectivity ( 7 3) in high yield via a chelated transition state. A Felkin transition state with the amide in the perpendicular position accounted for reduction with potassium triethylborohydride in ether at 0 C to give the stereochemi-cally pure anti diastereoisomer (55). The combination of these methods with asymmetric acylation provided an effective solution to the asymmetric aldol problem (Scheme 6). In contrast, the reduction of a-methyl-3-keto esters with zinc borohydride was highly syn selective when the ketone was aromatic or a,3-unsaturated, but less reliable in aliphatic cases. Hydrosilylation also provided complete dia-stereocontrol (Scheme 7). The fluoride-mediated reaction was anti selective ( 8 2) while reduction in trifluoroacetic acid favored production of the syn isomer (>98 2). No loss of optical purity was observed under these mild conditions. 

Although hydrosilanes reduce ketones, in trifluoroacetic acid, to the corresponding methylene compounds or dimeric ethers via ionic hydrogenation, the reduction of a-amino and a-oxy ketones and p-keto acid derivatives with hydrosilanes, particularly PhMe2SiH, under these conditions proceeded with high anti selectivity to the alcohols. No racemization was observed at the carbon a to the carbonyl group. Intramolecular hydrosilylation catalyzed by Lewis acids provided a highly stereoselective route to anti-1,3-diols from p-hydroxy ketones (Section 1.1.3. ). ... 

Branched-chain ketoaciduria (commonly known as Maple Syrup Urine Disease MSUD) is another ailment that may be caused by thiamine deficiency. In MSUD, the oxidative decarboxylation of alpha-keto acids derived from, i.e. valine, isoleucine, and leucine, is blocked due to an inadequate supply of the coenzyme thiamine pyrophosphate (TPP). Clinical symptoms of MSUD include mental and physical retardation. Describe briefly the structure of Riboflavin (Vitamin B-2) and its biochemical role. 

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