Chiral forms, amino acids

It is more difficult to prepare a chiral a,a-dialkylammo acid. Nevertheless, when such analogues are incorporated into the backbone of a peptide chain, analogues with modified properties are obtained. In this context, such residues have been evaluated as a new type of conformational constraint for the synthesis of enzyme-resistant agonists and antagonists of bioactive peptides. Here, the asymmetric synthesis or the resolution of the chiral quaternary amino acid is necessary and numerous procedures, which have recently been reviewed, were developed to produce the requisite amino acids in enantiomerically pure form. 

In the method for the preparation of chiral 2-amino acids 610, the amino functionality is protected by a bis(methylthio)methylene group (see Table 8). This group is conveniently removed by acid hydrolysis in the same step that the methoxymethyl and the amides groups are cleaved. The 2-amino acids are then isolated in pure form using ion-exchange techniques. 

A variety of chiral alignment media for organic solvents is known with the most widely used and best characterized being the poly(amino acids) PBLG and PCBLL. Both polymers form lyotropic mesophases and possess ot-helical structures for which many examples of enantiomeric differentiation have been shown. In addition to chiral poly(amino acids), it was demonstrated that achiral media with chiral cages like cyclodextrines serve as alignment media with the potential of chiral discrimination.121... 

Electrophilic amination is a general entry to chiral a-amino acids or functionalized P-amino and P-hydroxy a-amino acids with an anti stereochemistry. The chiral enolate technology has been applied for the obtaining of C-N bond-forming reactions with stereochemical control. 

Oxazolones (73), the saturated azlactones, have been studied intensively (B-57MI41801, B-57MI41802, 65AHC(4)75,69MI41800,77AHC(21)175). They show carbonyl and C=N absorptions in the 1820 and 1660 cm-1 regions, respectively. Azlactones derived from chiral a-amino acids, e.g. compound (74), can be obtained in optically active forms which racemize easily. The derived salts (75 R2 = H, Me or Ph) likewise exhibit optical activity they show intense carbonyl bands at 1890-1880 and C=N+ absorptions at ca. 1650 cm-. ... 

Chirality is a hallmark of many molecules from nature. Indeed, fhe number of chiral natural molecules is very large and the structural variety they represent is vast Among such substances - be they small molecules or macromolecules - an overwhelming majority occur in unichiral form. For example, chiral a-amino acids... 

D-form Amino acids tend to taste sweet, whereas L-forms are usually tasteless. This is again due to our chiral taste molecules. The smells of oranges and lemons are examples of the D and L enantiomers. 

An interesting group of chiral carriers are those formed by species that utilize interactions between transported enantiomer and transition metal complexes. For instance, such a compound, acting as an additional chiral ligand for the copper central cation, is able to recognize an amino acid Cu(II) complex present in the feed phase. This double chiral carrier-amino acid-Cu (II) complex becomes diastereoisomeric and can be transported through a... 

As a part of ongoing efforts to synthesize a potent, orally active anti-platelet agent, xemilofiban 1 [1], development of an efficient chemoenzymatic process for 2, the chiral yS-amino acid ester synthon (Fig. 1) was proposed. The scheme emphasized the creation of the stereogenic center as the key step. In parallel with the enzymatic approach, chemical synthesis of the / -amino acid ester synthon emphasized formation of a chiral imine, nucleophilic addition of the Reformatsky reagent, and oxidative removal of the chiral auxiliary. This chapter describes a selective amida-tion/amide hydrolysis using the enzyme Penicillin G amidohydrolase from E. coli to synthesize (R)- and (S)-enantiomers of ethyl 3-amino-5-(trimethylsilyl)-4-pen-tynoate in an optically pure form. The design of the experimental approach was applied in order to optimize the critical reaction parameters to control the stereoselectivity of the enzyme Penicillin G amidohydrolase. 

When L-amino acids (with the exception of proline) catalyzed the formose reaction, an excess of D-glyceraldehyde formed. In contrast, without any special catalyst, an equal mixture of the d- and L-glyceraldehyde formed. The reaction conditions were prebiotic. Furthermore, addition of small amounts of water increased the enantiomeric excess to more than 90% (Breslow et al. 2010). An intriguing mechanism of chiral induction takes place when chiral L-amino acids (such as the ones found in the Murchison meteorite) were used as basic catalysts in the formose reaction induced about 10% ee of D-threose (Pizzarello and Weber 2004). Stereo-selective syntheses of pentose sugars occur under realistic prebiotic conditions when LL-dipeptides catalyzed the formose reaction (Pizzarello and Weber 2010). 

Kunz and Pfrengle [96] introduced the formation of a-amino-acid derivatives by U-4CR with chiral O-acylated amino-carbohydrates like 2i and formic acid 3f. Usually, their products are formed relatively stereoselectively, and generally in good yield. It seems that the use of formic acid 3f proceeds in the U-4CRs better than do other acid components of 3A, as its amine components like 2i are sterically hindered. The essential disadvantage of the products 18p is that subsequent cleavage of its C-N bond into 33 and 34 can be accomplished only by strong acids such as HC1. Thus, it is doubtful if delicate chiral a-amino acid derivatives or peptides can be prepared successfully in this manner. 

Figure 11 Chirality of amino acids involved in forming heterocycles found in cyanobacterial natural products.

The synthesis of a-amino acid and peptide derivatives (86) whose newly formed amino acid unit corresponds to a chiral a-amino acid requires an asymmetric 4CC with a high degree of stereoselectivity. 

Formation of chiral a-amino acids from aminomalonic acids via decarboxylative protonation is readily accomplished in the presence of thiourea 1 (ex quinidine)/ The diaster-eomeric 2 (ex quinine) has been employed to generate monomethyl esters in chiral form by methanolysis meso-cydic anhydrides ... 

Piperazinediones are the keto forms of 2,5-dihydroxy-3,6-dihydropyrazines, and many 2,5-piperazinedione derivatives have been found in nature. Numerous synthetic investigations for these compounds <83H(20)1407, 93AHC(57)186> have been carried out, particularly in an approach to the total synthesis of the antibiotic bicyclomycin <85JA3253> and the synthesis of chiral a-amino acids known as the Schollkopf-Hartwig bislactim ether method. Direct introduction of a substituent on... 

Dimethoxy-3,6-dihydropyrazine (109), prepared by methylation of 2,5-piperazinedione with trimethyloxonium tetrafluoroborate, is susceptible to lithiation because the protons at C-3 and C-6 are activated by adjacent imine moieties. The lithium salt of this bislactim ether reacts with the 2-chloro-l-phenylsulfonyl alkene (110) to give the 3-substituted pyrazine (111) (Scheme 25) <89JCS(P1)453>. The bislactim ether from piperazinedione cyclo(L-Val—Gly) is lithiated with butyl-lithium and then treated with ketones, alkyl halides, or others to form, nearly stereospecifically, ran5-3-isopropyl-6-substituted piperazinediones due to the steric influence of the isopropyl group <828866, 838673). Similar stereoselective syntheses have been achieved in reactions starting from cyclo(L-Val—D,L-Ala) <828864, 918939). Acid hydrolysis of these products affords chiral a-amino acids. 

These weak acids ionize as R—COOH R—COO + H" ", where R = H . CH2 for glycine, R = H2NCH3(CH )4 for amino-n-capriotic acid, and R = CH3 for acetic acid. Glycine is the only protein-forming amino acid without a center of chirality, and amino-/t-capriotic. acid is the amino acid that is used to. treat hematological problems.]... 

Proteins are supermolecules that have been designed by nature to carry out certain specific tasks and to demonstrate distinctive properties. These molecules are built with a palette of 20 amino acids of which all but one, glycine, are chiral L-amino acids. The amino acids are strung together in a linear manner, like beads on a string, by way of peptide linkages, to form the backbone of the protein. The amino acid side chains stick out from this backbone. The architectural principles involved in constructing a supermolecule that can perform the required functions are described here. 

Earth s life forms. Careful analytical work proved that this optical activity was not the result of some Earth-based contaminant. In the past decade experiments have shown that with only the small amount of enantiomeric excess that these amino acids possess, some of them, such as the two shown below which have a fully substituted chirality center and cannot racemize, can effect a resolution of racemic amino acids through relatively simple processes such as crystallization. These events leave behind aqueous solutions of L-amino acids in high enantiomeric excess. Moreover, once these chiral L-amino acid solutions are generated, they can catalyze the enantiocontrolled synthesis of D-carbohydrates, which is what we all possess as well. As such, it is conceivable that the origin of chirality may well have come from outer space. 

Conjugate addition of the lithium salt of a chiral amine to a -substituted a, 3-unsaturated ester leads to formation of a chiral, nonracemic amino acid. Addition of the chiral, nonracemic lithium amide 5.143 (contains a phenethyl auxiliary) to 5.142 gave the amino-ester.63 Catalytic hydrogenation removed both benzylic groups (the auxiliary and the benzyl group) and acid hydrolysis of the ester moiety led to 3-amino-3-(4-benzyloxyphenyl)-propanoic acid, 5.144. The initial Michael adduct was formed with >99% dr (dr is diastereomeric ratio), leading to high enantioselectivity in 5.144 after removal of the auxiliary. 

Y. (2011) Dynamic kinetic resolution of a-aminonitriles to form chiral a-amino acids. Adv. Synth. Catal, 353, 2328-2332. 

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