A-amino acid proline

FIGURE 3-2 General structure of an amino acid. This structure is common to all but one of the a-amino acids. (Proline, a cyclic amino acid, is the exception.) The R group or side chain (red) attached to the a carbon (blue) is different in each amino acid. 

Since most often the selective formation of just one stereoisomer is desired, it is of great importance to develop highly selective methods. For example the second step, the aldol reaction, can be carried out in the presence of a chiral auxiliary—e.g. a chiral base—to yield a product with high enantiomeric excess. This has been demonstrated for example for the reaction of 2-methylcyclopenta-1,3-dione with methyl vinyl ketone in the presence of a chiral amine or a-amino acid. By using either enantiomer of the amino acid proline—i.e. (S)-(-)-proline or (/ )-(+)-proline—as chiral auxiliary, either enantiomer of the annulation product 7a-methyl-5,6,7,7a-tetrahydroindan-l,5-dione could be obtained with high enantiomeric excess. a-Substituted ketones, e.g. 2-methylcyclohexanone 9, usually add with the higher substituted a-carbon to the Michael acceptor ... 

Some workers avoid delay. Pai)adium-on-carbon was used effectively for the reductive amination of ethyl 2-oxo-4-phenyl butanoate with L-alanyl-L-proline in a synthesis of the antihyperlensive, enalapril maleate. SchifTs base formation and reduction were carried out in a single step as Schiff bases of a-amino acids and esters are known to be susceptible to racemization. To a solution of 4,54 g ethyl 2-oxO 4-phenylbutanoate and 1.86 g L-alanyl-L-proline was added 16 g 4A molecular sieve and 1.0 g 10% Pd-on-C The mixture was hydrogenated for 15 hr at room temperature and 40 psig H2. Excess a-keto ester was required as reduction to the a-hydroxy ester was a serious side reaction. The yield was 77% with a diastereomeric ratio of 62 38 (SSS RSS)((55). 

The amino acids proline and hydroxyproline exert a stabilizing influence on the triple helix as described in detail in Sect. 4.5. By examining the CB peptides of collagen, a structural stability which is directly proportional to the itnino acid content may thus be found. It has, however, not been possible to synthesize model peptides displaying structural stability comparable to that of the native peptides having corresponding amino acid contents. 

Palladium-catalysed asymmetrie allylations of various carbonyl compounds have been studied by Hiroi et al. using various types of chiral sulfonamides derived from a-amino acids. In particular, the chiral bidentate phosphinyl sulfonamide derived from (5)-proline and depicted in Scheme 1.63 was employed in the presence of palladium to eatalyse the allylation of methyl aminoacetate diphenyl ketimine with allyl aeetate, leading to the eorresponding (7 )-product with a moderate enantioseleetivity of 62% ee. This ligand was also applied to the allylation of a series of other nueleophiles, as shown in Seheme 1.63, providing the eorresponding allylated produets in moderate enantioseleetivities. 

Catalytic Enantioselective Reduction of Ketones. An even more efficient approach to enantioselective reduction is to use a chiral catalyst. One of the most developed is the oxazaborolidine 18, which is derived from the amino acid proline.148 The enantiomer is also available. These catalysts are called the CBS-oxazaborolidines. 

Dipolar cycloadditions of the unusual dipolarophiles 9-arylidenefluorenes 446 with the dipoles generated from isatin 432a and cyclic amino acid proline 433a were carried out under four different conditions to yield a series of novel dispiro oxindole derivatives 50a-f via [3+2] cycloaddition (Scheme 100) <2002T8981>. 

Herbivores that commonly feed on tannin-rich plants have evolved interesting methods to lessen the effect of ingested tannins on their digestive systems. For example, the salivary proteins of rabbits and other rodents are high in the amino acid proline, which has a very high affinity for tannins. Eating food high in tannins stimulates the secretion of these proteins and diminishes the toxic effect of the tannins. 

A series of l/f-pyrrolo[2,l-r][l,4]oxazin-l-ones 196 are also the product of an LJgi multicomponent reaction between proline (and also other a-amino acids that gave the corresponding monocyclic compounds) and several isonitriles in the presence of commercially available glycolaldehyde dimer (Equation 3) <20010L4149>. 

Efforts to find potent and selective DPP-4 inhibitors in the a-amino acid amide series were made in parallel with those in the (3-amino acid amides series. The structural origin of the earliest P-amino acid amide DPP-4 inhibitors traces back to two Merck HTS hits proline derivative 25 and piperazine derivative 26. These two screening leads were further progressed to P-amino acid amide DPP-4 inhibitors incorporating thiazolidine, proline and piperazine amide moieties (Figure 17.5). 

There are approximately 20 amino acids found in proteins, all of which are a-amino acids with the exception of the two a-imino acids proline and hydrox-yproline (Figure 10.2), which for the purpose of this discussion will be considered with the amino acids because of their similarity. The a-amino acids are so called because the amino group is attached to the a-carbon of the chain which is, by convention, the carbon atom adjacent to the carboxyl group. Succeeding carbon atoms are designated 8, y, S and e (Figure 10.3). Hence in... 

Ninhydrin (triketohydrindene hydrate) reacts with an amino acid when heated under acidic conditions (pH 3-4) to produce ammonia, carbon dioxide and a blue-purple complex. This reaction forms the basis of many widely used methods (Figure 10.11). One mole of carbon dioxide is liberated from each mole of amino acid, exceptions being the dicarboxylic amino acids, which produce two moles of carbon dioxide, and the a-imino acids, proline and hydroxyproline, which do not produce carbon dioxide. Although this formed the basis of a gasometric technique, colorimetric methods are now the most common. 

Primary amino acids will react with o-phthalaldehyde in the presence of the strongly reducing 2-mercaptoethanol (pH 9-11) to yield a fluorescent product (emission maximum, 455 nm excitation maximum, 340 nm). Peptides are less reactive than a-amino acids and secondary amines do not react at all. As a result, proline and hydroxyproline must first be treated with a suitable oxidizing agent such as chloramine T (sodium A-chloro-p-toluene-sulphonamide) or sodium hypochlorite, to convert them into compounds which will react. Similarly cystine and cysteine should also be first oxidized to cysteic acid. 

So what does this magical molecule do Actually, it does two things, one rather more crystalline clear than the other. The crystal clear thing that ascorbic acid does is act as coenzyme for an enzyme known as prolyl hydroxylase. This enzyme catalyzes the conversion of the amino acid proline to hydroxyproline, a major, if exotic, amino acid in the structural protein collagen ... 

Vitamin C is essential for the formation of collagen, the principal structural protein in skin, bone, tendons, and ligaments, being a cofactor in the hydroxylation of the amino acids proline to 4-hydroxyproline, and of lysine to 5-hydroxylysine. These hydroxyamino acids account for up to 25% of the collagen structure. Vitamin C is also associated with some other hydroxylation reactions, e.g. the hydroxylation of tyrosine to dopa (dihydroxyphenylalanine) in the pathway to catecholamines (see Box 15.3). Deficiency leads to scurvy, a condition characterized by muscular pain, skin lesions, fragile blood vessels, bleeding gums, and tooth loss. Vitamin C also has valuable antioxidant properties (see Box 9.2), and these are exploited commercially in the food industries. 

Direct electrochemical oxidation of protected a-amino acids is generally ineffective. An exception is provided by proline derivatives, which are methoxylated on carbon-5 of the pyrrolidine ring. Open chain protected a-amino acids undergo... 

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