A-Ami no acid

Compared to the parent a-amino acids, /9-amino acids are characterized by a much greater chemical diversity (five substitution positions versus three for a-ami-no acids) and conformational versatility. With the extra carbon atom in the backbone, the number of possible configurational isomers for / -amino acids increases dramatically (eight possible configurations versus two for a-amino acids) (Fig. 2.5). 

In a similar way, chiral, nonracemic 5-alkyl-4-imidazolidinones 8 can be prepared from chiral, nonracemic a-ami no acids 53. The enantiomerically pure starting material is transformed into the intermediate imine 6, which is cyclized with acid, then A -acylated. The major diastereomer, the more stable /ram-isomer, is obtained enantiomerically pure. The minor, enantiomerically pure ci.s-isomer can also be isolated from this product mixture3. Alternatively, the civ-isomer can be prepared by heating the imine 6 with benzoic acid anhydride, which results in a good yield and d.r. However, due to some raeemization during the reaction, the ee is <100%. 

Hydrolyze Schiff base Release a-keto acid and pyridoxamine phosphate Transfer of amino group from pyridoxamine phosphate to pyruvate, forming alanine occurs by reversal of these steps. Other transaminases use other a-ami no acids and a-keto acids. 

The virtual screening of the CAP database using hypothesis 1 as a query was organized in several rounds. The first round was focused on unprotected a-ami-no acids of low molecular weight (below 300 g mol-1) because this subset is expected to contain more hits with possibilities of optimizing them. Some results of this first virtual screening round are reported in Table 15.2. 

Stereoselective rearrangement reactions can involve sugar-linked functionalities. An example of this type is the Overman rearrangement of allylic trichloracetimidates formed from a D-glucofuranose derivative 20 [36]. This methods affords (L)-a-ami-no acids 25 from (Z)-allylic imidate 23 and (R)-a-amino acids 25 from ( )-imidates 23 with a diastereoselectivity of about 16 1. The oxidative cleavage of compound 24 with Ru04 yields the a-amino acid 25, (Scheme 15). 

S R ratio = 5 1) [22]. Yanada and Yoneda constructed the deazaflavinophane 26, which exhibits complete facial selectivity in its oxidation and reduction reactions, e.g. the reduction with NaBD to afford 27 [23], Belokon and Rozen-berg used scalemic 4-formyl-5-hydroxy[2.2]para-cyclophane (FHPC) 28 in the synthesis of a-ami-no acids (ee 45-98 %) [24], An alternative approach to FHPC was more recently reported by Hopf [25]. Other interesting advances in the area of chiral cyclophanes include the homochir-al [2.2]paracyclophane-derived amino acids 29 and 30 [26], as well as (5)-PHANEPHOS (31) [27], which has been shown to be an effective ligand for highly enantioselective Ru-catalyzed asymmetric hydrogenations of -ketoesters and... 

An enzyme that catalyzes the deamination of a-ami-no acids by dehydrogenation to keto acids and ammonia. Two types are recognized, acting on the d-and L-amino acids. Recent emphasis has been on characterization of the D-amino oxidase, which is known to contain the flavin isoalloxazine as coenzyme. Both types are found in animal tissue, especially in liver and kidney, as well as in snake venom and certain bacteria. 

The biotransformation of prochiral a-keto acids into the corresponding L-amino acids represents an interesting asymmetric reaction for the production of L-a-ami-no acids. In this reaction two enzymes, namely leucine dehydrogenase (LeuDH... 

Subtle differences in acidity can sometimes be used to discriminate between two hydroxyl functions (Scheme 58). In these cases, p-nitrobenzenesulfonyl chloride appears to be the reagent of choice. Not only does it display improved chem-oselectivity for the most acidic hydroxyl function, but it also acts as a better leaving group. This strategy was employed to prepare, inter alia, substituted a-ami-no acids 225 [127a],glycidic esters 226 [127a] and chloramphenicol 227 [139]. 

On the other side these simple systems provide unique information about relationship between chiroptical properties of suitable chromophores and geometry of the macromolecules. Such information is of great help for interpreting more complicated data of poly-a-ami no acids and proteins [sij. ... 

Recent efforts in the development of efficient routes to highly substituted yS-ami-no acids based on asymmetric Mannich reactions with enantiopure sulfmyl imine are worthy of mention. Following the pioneering work of Davis on p-tolu-enesulfmyl imines [116], Ellman and coworkers have recently developed a new and efficient approach to enantiomerically pure N-tert-butanesulfmyl imines and have reported their use as versatile intermediates for the asymmetric synthesis of amines [91]. Addition of titanium enolates to tert-butane sulfmyl aldimines and ketimines 31 proceeds in high yields and diastereoselectivities, thus providing general access to yS -amino acids 32 (Scheme 2.5)... 

Fig. 2.27 The two types of extended /1-peptide strands with conformation requirements around the C(a)-C(/1) bonds. (A) Parallel and antiparallel polar sheets with antiperiplanar conformations around the C(a)-C fl) bond are promoted by unlike-fi -ami-no acids with alkyl side-chains. Antiperiplanar side-chains at C(a) and C(/3) occupy positions approximately perpendicular to the amide planes. (B) Extended strands formed by alternating +)-sc and (-)-sc conformations...

In contrast to these examples, the antibacterial agent piromidic acid (5.91, Fig. 5.24) is not converted to a lactam derivative but yields only the cw-ami-no acid derivative [188]. Steric features might underlie this metabolic difference. Bulky groups in close proximity to the N-atom seem to favor the formation of the amino acid metabolite, whereas substrates with an unhindered N-atom seem to favor the formation of a lactam metabolite. 

At this stage, it is clear that ribosomal protein synthesis will not allow the incorporation of D-amino acids or those that are too bulky, and that only a-ami-no and a-hydroxy acids can be introduced those with extended backbones such as y-amino acids cannot be introduced in this manner. Also, in spite of the development of improved suppressor tRNAs, the incorporation of small, highly polar amino acids remains difficult. 

Oxime reduction is a very efficient procedure for obtaining racemic A7-hydroxy ami no acids in good yields. 19 31-361 TV-Hydroxylamine and O-protected A-hydroxylamines react smoothly and rapidly with a-oxo acid derivatives 23 to give the corresponding oximes 24. Acids 24 (R2= OH) can be reduced with NaBH3CN or LiBH3CN (Scheme 7) to give TV-hydroxyamino acids 25 (R2= OH)/31 but reaction yields are unsatisfactory for esters 24 (e.g., R2= OEt) or... 

The outstanding chemical property of cyanohydrins is Ihe ready conversion to a-hydroxy acids and derivatives, especially a-ami no and a./J-unsaiuratcd acids. Because cyanohydrins are primarily used as chemical intermediates, data on production and prices arc not usually published. The industrial significance of cyanohydrins Is waning as more direct and efficient routes to the desired products are developed. 

Hanessian, S., Luo, X., and Schaum, R. (1999) Synthesis and folding preferences of i/-ami no acid oligopeptides stereochemical control in the formation of a reverse turn and a helix. Tetrahedron Lett. 40,4925 1929. 

The cycle of dcproceetton, coupling, and a axKi] ia repeated aa many timee as desired to add ami no acid units to the crowing chain ... 

Rhodium-Catalyzed Asymmetric Hydrogenation of Olefins. MiniPHOS (1) can be used in rhodium-catalyzed asymmetric hydrogenation of olefinic compounds. The complexation with rhodium is carried out by treatment of 1 with [Rh(nbd)2]BF4in THF (eq 2). The hydrogenation of a-(acylamino)acrylic derivatives proceeds at room temperature and an initial H2 pressure of 1 or 6 atm in the presence of the 0.2 mol% MiniPHOS-Rh complex 2. The reactions are complete within 24—48 h to afford almost enantiomerically pure a-amino acids (eq 3). Itaconic acids, enamides, and dehydro-3-ami no acids can also be hydrogenated with excellent enantioselectivity (eq 4—6). 

Peptide synthesis. This is an excellent reagent for the preparation of activated p-nitrophenyl esters of N-protected amino acids. A solution of the N-protected ami no acid (2) in acetic acid containing a little pyridine is treated with 1.5 equivalents... 

FIGURE 124-11. Protein synthesis. When a specific protein is needed, the portion of DNA responsi-blefor that protein unwinds, exposingthe necessary nucleotide sequence. Complementary nucleotides are assembled to form messenger RNA (mRNA), which travels to ribosomes in the cytoplasm. There, transfer RNA (tRNA) matches ami no acids to the nucleotide sequence on the mRNA. The amino acids are assembled to form proteins. 

The enantioselective hydrolysis of racemic N-acetylated a-amino acids d,l-1 at De-gussa represents a long established large-scale process for the production of L-ami-no acids, l-2 [4]. This enzymatic resolution requires an L-aminoacylase as the biocatalyst. The starting materials for this process are readily available, since racemic N-acetyl amino acids d,l-1 can be economically synthesized by acetylation of racemic a-amino acids with acetyl chloride or acetic anhydride under alkaline conditions via the so-called Schotten-Baumann reaction [5]. The enzymatic resolution reaction of N-acetyl d,L-amino acids, d,l-1, is achieved by a stereospecific L-aminoacylase which hydrolyzes only the L-enantiomer and produces a mixture of the corresponding L-amino acid, l-2, acetate, and N-acetyl D-amino acid, d-1 (Fig. 4) [6],... 

PEPTIDE BOND FORMATION Polypeptides are linear polymers composed of amino acids linked together by peptide bonds. Peptide bonds (Figure 5.11) are amide linkages formed when the unshared electron pair of the a-ami no nitrogen atom of one amino acid attacks the a-carboxyl carbon of another in a nucleophilic acyl substitution reaction. A generalized acyl substitution reaction is shown ... 

P-Ami no acids, although of less importance than their oc-analogues, are also present in peptides and different heterocycles, and their free forms and derivatives exhibit interesting pharmacological effects [1]. A number of syntheses and transformations have been performed on their stereoisomeric alicyclic analogues (e.g. 1-3). Until recently, the investigations were mainly of academic interest since no naturally-occurring compounds were known. 

Although only L-amino acids occur in proteins, D-ami-no acids are often a part of the metabolism of lower organisms.The antibiotic actinomycin D, for example, contains a unit of D-valine, and the antibiotic bacitracin A contains units of D-asparagine and D-glutamic acid. Draw Fischer projections and three-dimensional representations for these three D-amino acids. 

A. may consist of either one polypeptide chain or of 2 or 4 homologous or heterologous subunits. Eukaryotic cells contain more than different A., because mitochondria and plastids have their own ami-no-acid-spedfic A., which differ in their specificity toward homologous tRNA from those of the cytoplasm. Some A. are able to load several amino-acid-specific tRNAs, e.g. leucyl-tRNA synthetase of . coli, which can load 5 different spedes of tRNA, . 

Human defensins are synthesized as 94- to 100-ami no-acid preprodefensins that contain a conserved 19 amino-acid N-terminal signal sequence that targets the peptide to the endoplasmic reticulum. TTiis is followed by an anionic propiece, proposed to balance the cationic charge of the defensin (9). 

L-(-)-7-Ami no-a-hydroxybutyric Acid N-hydroxysuccinim ide 6 -Monobenzyloxy[Pg.58]

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