Elimination reactions, amino acid

Racemisation of L-amino acids (elimination of an a-proton of protein bound amino acids) occurring in vivo during aging and some diseases (Alzeheimer s disease, cataracts and diabetes) is facilitated by reducing sugars. An example is the reaction of D-glucose shown in Figure 2.40. In essence, the Amadori product formed in the MaiUard reaction (see Section 4.7.5) isomerises and is hydrolysed to a mixture of L-and n-amino acids under the formation of 3-deoxy-D-erythro-hexos-2-ulose or 1-deoxy-n-erythro-hexo-2,3-diulose. 

Another protecting group of amines is 1-isopropylallyloxycarbonyl, which can be deprotected by decarboxylation and a /3-elimination reaction of the (tt-l-isopropylallyl)palladium intermediate under neutral conditions, generating CO2 and 4-methyl-1,3-pentadiene. The method can be applied to the amino acid 674 and peptides without racemization[437]. 

Zaitsevs rule (Section 5 10) When two or more alkenes are capable of being formed by an elimination reaction the one with the more highly substituted double bond (the more sta ble alkene) is the major product Zwitterion (Section 27 3) The form in which neutral amino acids actually exist The ammo group is in its protonated form and the carboxyl group is present as a carboxylate... 

FIGURE 1.9 (a) Amino acids build proteins by connecting the n-carboxyl C atom of one amino acid to the n-amino N atom of the next amino acid in line, (b) Polysaccharides are built by combining the C-1 of one sugar to the C-4 O of the next sugar in the polymer, (c) Nucleic acids are polymers of nucleotides linked by bonds between the 3 -OH of the ribose ring of one nucleotide to the 5 -P04 of its neighboring nucleotide. All three of these polymerization processes involve bond formations accompanied by the elimination of water (dehydration synthesis reactions). 

The biologically active form of vitamin Bg is pyridoxal-5-phosphate (PEP), a coenzyme that exists under physiological conditions in two tautomeric forms (Figure 18.25). PLP participates in the catalysis of a wide variety of reactions involving amino acids, including transaminations, a- and /3-decarboxylations, /3- and ") eliminations, racemizations, and aldol reactions (Figure 18.26). Note that these reactions include cleavage of any of the bonds to the amino acid alpha carbon, as well as several bonds in the side chain. The remarkably versatile chemistry of PLP is due to its ability to... 

A 1,8-naphthyridine, nalidixic acid (39), shows clinically useful antibacterial activity against Gram-negative bacteria as such, the drug is used in the treatment of infections of the urinary tract. Condensation of ethoxymethylenemalonate with 2-amino-6-methylpyridine (36) proceeds directly to the naphthyri-dine (38) the first step in this transformation probably involves an addition-elimination reaction to afford the intermediate, 37. W-Ethylation with ethyl iodide and base followed by saponification then affords nalidixic acid (39). 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

Thus, in contrast to benzothiepins, dibenzo compounds can be synthesized by direct acid-catalyzed elimination of water from hydroxy derivatives, or of amines from amino derivatives, at elevated temperatures due to their thermal stability. As in the case of benzothiepins, dibenzo derivatives can also be prepared by base-catalyzed elimination from the corresponding halo derivatives however, the yields are somewhat lower compared to the acid-catalyzed reactions. As a special case, an aziridine derivative was deaminated by palladium-catalyzed hydrogenation to afford the corresponding dibenzothiepin.69... 

Pyridoxal phosphate mainly serves as coenzyme in the amino acid metabolism and is covalently bound to its enzyme via a Schiff base. In the enzymatic reaction, the amino group of the substrate and the aldehyde group of PLP form a Schiff base, too. The subsequent reactions can take place at the a-, (3-, or y-carbon of the respective substrate. Common types of reactions are decarboxylations (formation of biogenic amines), transaminations (transfer of the amino nitrogen of one amino acid to the keto analog of another amino acid), and eliminations. 

Proteins form in a sequence of condensation reactions in which the amine end of one amino acid combines with the carboxyl end of another, eliminating a water molecule to create an amide linkage. The amide group that connects two amino acids is called a peptide linkage, and the resulting molecule is known as a peptide. When two amino acids are linked, the product is a dipeptide. A dipeptide formed from alanine and glycine is shown in Figure 13-33. 

P-Bromonaphthalene. The preparation from p-naphthylamine, which has carcinogenic properties, is avoided by the use of 2-naphthylamine-1-sulphonic acid ( 2-amino-1-naphthalenesulphonic acid ) the latter is obtained commercially by cautious treatment of p-naphthol with sulphuric acid—the SOjH group first enters the 1-position—followed by the Bucherer reaction. Diazotisation and reaction with cuprous bromide yields 2-bromonaphthalene-l-sulphonic acid heating with sulphuric acid eliminates the sulphonic acid group to give 2-bromonaphthalene. 

Amino acids activated at the amino group by a benzotriazolide moiety react with amino acids under elimination of benzotriazole and C02 to give peptides. Reaction is achieved by warming up equimolar amounts of the components in anhydrous acetonitrile or aqueous acetone.[45] The benzotriazolylcarbonylamino acids are prepared from benzo-triazolyl-1-carboxylic acid chloride and amino acids.[46]... 

X,P-Dehydro-a-amino acids are prepared by elimination of HN02 from P-nitro-a-amino acids, which are prepared by reaction of a-bromoglycine derivatives with alkyl nitronates (see Eq. 7.135).181 This process is a new type of the Michael addition of nitro compounds followed by elimination of HNOz. Such unusual amino acids are interesting as enzyme inhibitors.182... 

The linking up of amino acids can be described as a polycondensation reaction involving elimination of water the result is the formation of peptide bonds. 

It is truly amazing under what conditions, using completely different methods, amino acids can be linked up with elimination of water. Thus, it has been known for years that micelles (see Sect. 10.2) can catalyse various types of reactions in aqueous media, e.g., hydrolysis or aminolysis. Micelles are aggregates which form in aqueous solution from tensides under certain conditions (temperature, concentration). Cetyltrimethylammonium bromide (Cl llr J micelles (this... 

Some reactions have been found to proceed with better results in the absence of solvent, probably because of the creation of temperature gradients which are eliminated in the presence of a stirred solvent. This was observed for the Diels-Alder reaction of a-amino acid precursors with cyclopentadiene catalyzed by heterogeneous catalysts (Si02-Al, Si02-Ti), when the reaction was performed in toluene or in the absence of solvent [53], Microwave activation increased the rate of reaction without reducing the selectivity of the reaction. 

These enzymes invariably involve a cofactor, pyridoxal phosphate (vitamin B6). In addition, pyridoxal phosphate is also required for most decarboxylations, racemizations, or elimination reactions in which an amino acid is a substrate. Pyridoxal phosphate is not involved in decarboxylations in which the substrate is not an amino acid. So if a question... 

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