Amino acid asymmetry

The unit cell considered here is a primitive (P) unit cell that is, each unit cell has one lattice point. Nonprimitive cells contain two or more lattice points per unit cell. If the unit cell is centered in the (010) planes, this cell becomes a B unit cell for the (100) planes, an A cell for the (001) planes a C cell. Body-centered unit cells are designated I, and face-centered cells are called F. Regular packing of molecules into a crystal lattice often leads to symmetry relationships between the molecules. Common symmetry operations are two- or three-fold screw (rotation) axes, mirror planes, inversion centers (centers of symmetry), and rotation followed by inversion. There are 230 different ways to combine allowed symmetry operations in a crystal leading to 230 space groups.12 Not all of these are allowed for protein crystals because of amino acid asymmetry (only L-amino acids are found in proteins). Only those space groups without symmetry (triclinic) or with rotation or screw axes are allowed. However, mirror lines and inversion centers may occur in protein structures along an axis. 

The asterisk signifies an asymmetric carbon. AH of the amino acids, except glycine, have two optically active isomers designated D- or L-. Isoleucine and threonine also have centers of asymmetry at their P-carbon atoms (1,10). Protein amino acids are of the L-a-form (1,10) as illustrated in Table 1. 

Induction of Asymmetry by Amino Acids. No fewer than sis types of reactions can be carried out with yields of 75—100% usiag amino acid catalysts, ie, catalytic hydrogenation, iatramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosdylation, and epoxidations (91). 

Reductive alkylation with chiral substrates may afford new chiral centers. The reaction has been of interest for the preparation of optically active amino acids where the chirality of the amine function is induced in the prochiral carbonyl moiety 34,35). The degree of induced asymmetry is influenced by substrate, solvent, and temperature 26,27,28,29,48,51,65). Asymmetry also has been obtained by reduction of prochiral imines, using a chiral catalyst 44). Prediction of the major configurational isomer arising from a reductive alkylation can be made usually by the assumption that amine formation comes via an imine, not the hydroxyamino addition compound, and that the catalyst approaches the least hindered side (57). 

The complex obtained from commercially available chiral a-amino acids (AA) with Cu + ion induces asymmetry in the Diels-Alder reaction of 31 (R = H) with 32. By using 10% Cu(II)-AA (AA = L-abrine) the cycloaddition occurs e/iJo-stereoselectively in 48 h at 0°C with high yield and with acceptable enantioselectivity ee = 1A%). This is the first example of enantioselective Lewis-acid catalysis of an organic reaction in water [9b]. 

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. 

Warmerdam, E.G.J.C., van Rijn, R.D., Brussee, J. et al. (1996) Synthesis of a-hydroxy-/3-amino acids from chiral cyanohydrins. Tetrahedron Asymmetry, 7, 1723-1732. 

Affinity liquid chromatography, 7, 8 Amino acid, 67, 74 Asymmetry 04s), 39... 

The molecular asymmetry of 9 is due to the four axial pendants containing the chiral L-vahne group. The efficiency of the gas-phase exchange reaction 30 where A are representative amino acids and B is either (5)-(- -)- or R)- — )-2-butylamine is appreciably affected by the configuration of both A and B. The guest exchange kinetic results are reported in Table 17. The presence of more than one reacting [9-H-A]" structure is observed with A = DOPA. A similar behavior was observed with permethylated /8-CD as the host." " ... 

Yasuda, M., Ueda, M., Muramatsu, H., Mihara, H. and Esaki, N., Enzymatic synthesis of cyclic amino acids by A-methyl-L-amino acid dehydrogenase from Pseudomonas putida. Tetrahedron Asymmetry. 2006, 17, 1775. 

FIGURE 2.15 Separation of a P-amino acid on a A-40,926 CSP. (From D Acquarica, I. et al., Tetrahedron Asymmetry, 11, 2375, 2000. With permission from Elsevier, Copyright (2000).)... 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

In the present review we concentrate on the induction of asymmetry for the case in which the chiral reagent (5) is represented by an amino acid or a derivative thereof. Only those papers are considered in which the formation of a new center of asymmetry is induced. This can take place with the simultaneous incorporation of the chiral amino acid (or a derivative thereof) in the target molecule or by the action of catalytic amounts of this amino acid on a prochirale molecule. Reactions in which only the asymmetric center of the amino acid is modified without the stereoselective appearance of a new chiral center, have not been considered. Enzymatically catalyzed transformations 241 of molecules are not treated here. 

Induction of Asymmetry by Catalytic Amounts of Amino Acids or their Derivatives... 

In the preceding Section we considered the catalytic asymmetric synthesis. In this connection the induction of asymmetry by catalytic amounts of chiral information (= amino acids or their derivatives) was treated. The chiral information was transferred into a prochiral substrate. 

In Section 3 we turn to reactions which require at least equimolar amounts of chiral information for the induction of asymmetry in the products. The newly formed asymmetric center can be induced by either intramolecular or by intermolecular interactions. Having served its stereochemical purpose, the amino acid moiety may be destroyed so that it does not exist as a discrete entity in the product, although sections of it may survive. 

The asymmetric Strecker synthesis was also applied in the preparation of other chiral products. In these reactions japanese chemists 141> always used amino acid derivatives as the chiral amine component which is responsible for the induction of asymmetry. 

Elaridi, J., Thaqi, A., Prosser, A., Jackson, W.R. and Rohinson, A.J. An Enantioselective Synthesis of -Amino Acid Derivatives. Tetrahedron Asymmetry 2005, 16, 1309-1319. 

Kubryk, M. and Hansen, K.B. Apphcation of the Asymmetric Hydrogenation of Enamines to the Preparation of a Amino Acid Pharmacophore. Tetrahedron Asymmetry 2006,17, 205-209. 

In a number of nonenzymatic reactions catalyzed by pyridoxal, a metal ion complex is formed—a combination of a multivalent metal ion such as cupric oi aluminum ion with the Schiff base formed from the combination of an amino acid and pyridoxal (I). The electrostatic effect of the metal ion, as well as the electron sink of the pyridinium ion, facilitates the removal of an a -hydrogen atom to form the tautomeric Schiff base, II. Schiff base II is capable of a number of reactions characteristic of pyridoxal systems. Since the former asymmetric center of the amino acid has lost its asymmetry, donation of a proton to that center followed by hydrolytic cleavage of the system will result in racemic amino acid. On the other hand, donation of a proton to the benzylic carbon atom followed by hydrolytic cleavage of the system will result in a transamination reaction—that is, the amino acid will be converted to a keto acid and pyridoxal will be converted to pyridoxamine. Decarboxylation of the original amino acid can occur instead of the initial loss of a proton. In either case, a pair of electrons must be absorbed by the pyridoxal system, and in each case, the electrostatic effect of the metal ion facilitates this electron movement, as well as the subsequent hydrolytic cleavage (40, 43). 

To obtain amino acids, amino carbenes (X = NH2 in Fig. 6) must be used, and if chirality is required, the asymmetry of the new a-carbon center must be controlled. Higedus and co-workers have achieved good stereochemical control by using a chiral oxazolidine chromium carbene. 

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