Racemization amino acids properties

As pointed out previously, all of the amino acids prepared in this section are racemic. To obtain an enantiopure amino acid requires separation of the enantiomers via resolution. As discussed in Chapter 9 (Section 9.2), the physical properties of enantiomers are identical except for specific rotation. Because separation methods rely on differences in physical properties, this is a problem. It is overcome if the racemic amino acid mixture reacts with a reagent that has a stereogenic center. The resulting product will be a mixture of diastereomers, which have different physical properties and may be separated. 

In many cases only the racemic mixtures of a-amino acids can be obtained through chemical synthesis. Therefore, optical resolution (42) is indispensable to get the optically active L- or D-forms in the production of expensive or uncommon amino acids. The optical resolution of amino acids can be done in two general ways physical or chemical methods which apply the stereospecific properties of amino acids, and biological or enzymatic methods which are based on the characteristic behavior of amino acids in living cells in the presence of enzymes. 

The use of the relative proportions and racemization properties of amino acids as a means of identifying contaminated samples would have several advantages. First of all, modern amino acid analyzers are very sensitive analytical instruments. Systems are... 

The use of D-AAO from the yeast Rhodotorula gracilis to deracemize naphthyl amino acids has been studied in some detail by the groups of Servi and Pollegioni, who compared the kinetic properties of the enzyme with racemic 1- and 2-naphthylalanine (1 and 2) and 1- and 2-naphthylglycine (3 and 4). 

Due to recombination of the carboanion (see Figure 13.4) with a proton, both enantiomeres l and d of the amino acids can be formed. The rate of racemization depends on the properties of the amino-acid residues and of the proteins. It is generally about ten times higher in amino-acid residues in proteins than in free amino acids. 

The polymerization of enantiomerically pure monomers presents no relevant stereochemical problems when the asymmetric carbon atom is not involved in the reaction and no new centers of stereoisomerism are formed. This is the case, for example, in polycondensation of chiral diacids with diamines (274) and in ring-opening polymerization of substituted lactams (275) and A -carboxyanhy-drides of a-amino acids (276). Interest here lies mainly in the properties of the polymer. Accidental racemization may sometimes occur but is not necessarily related to the mechanism of polymerization. 

Monoamine oxidases are enzymes that catalyze the racemization of ot-amino acids 186). Both l- and D-selective monoamine oxidases are known (i.e., they catalyze the racemization of either S)- or (R)-enantiomers of amino acids). This property has been exploited to obtain enantiomerically pure (R) and S) amino acids by using an appropriate achiral reducing agent such as NaBH4, NaB(CN)H3, or H3N BH3 in combination with an l- or D-selective monoamine oxidase 187). 

The enantioselective binding properties of certain chiral crown ethers have been employed in the resolution of amino acid racemates. The racemic amino ester is adsorbed onto silica gel as its ammonium salt and eluted by a chloroform solution of the chiral crown ether. An excellent separation of the two enantiomers is achieved by this method (74JA7100). 

A number of methods for the synthesis of piperazic acid (7) and related derivatives are currently available as a result of growing interest in natural product chemistry and in their potential in medicinal chemistry. Their chemistry and conformational properties have been comprehensively reviewed. 2451 Racemic piperazic acid is obtained by condensation of penta-2,4-dienoic acid with phthalazinedione and subsequent reductive deprotection of the resulting A,A -bis(phthaloyl)-l,2,3,6-tetrahydropyridazine-3-carboxylic acid.12431 Resolution of racemic piperazic acid is achieved by fractional crystallization of the ephedrine salt of Nl-(benzyloxycarbonyl)piperazic acid from ethyl acetate. 246,2471 A typical route to enantiomerically pure (3S)-piperazic acid 56 starts from chiral 2-amino-5-hydroxyvaleric acid 55 as shown in Scheme 12.1248 Convenient stereoselective syntheses have been reported for 5-hydroxy- and 5-chloropiperazic acids as important constituents of natural cyclic peptides and depsipep-tides.1249,2521... 

The biological properties of phosphorus amino acid analogues (and their derivatives) depend upon their stereochemistry. Consequently, numerous methods for obtaining these compounds in stereochemically pure form have been developed. Two excellent review articles summarize the work performed prior to 1993. 3,4 Resolution of racemates continues to be a useful approach for obtaining optically pure aminoalkylphosphonic and -phosphinic acid derivatives (vide infra), but most of the newer literature describes asymmetric syntheses of these compounds.15-17 Two methods for resolution and one for asymmetric synthesis are described (vide infra) they have been selected since they are relatively easy to perform, work with a variety of side chains, can be carried out on a reasonable scale with readily available starting materials, and produce products of high stereopurity. However, just as in traditional amino acid chemistry, each side chain introduces its own complications, and in many cases, especially for more complex analogues, other methods may be preferred. 

The hydrolysis of proteins yields a complex mixture of amino acids having closely related physical properties. Although a quantitative separation of the individual amino acids can be achieved by chromatographic methods, only in a few cases is the preparative isolation of an individual member worth while. Provided that racemisation is avoided during hydrolysis, however, amino acids are obtained in this way in the optically active form. The normal synthetic products are of course racemic, but they may be resolved by appropriate procedures (e.g. the enzymic method described in Expt 5.221). 

A kinetic resolution is a chemical reaction in which one enantiomer of a racemate reacts faster than the other. Most kinetic resolutions of pharmaceutical compounds are catalyzed processes. Catalysts used in a kinetic resolution must be chiral. Binding of a chiral catalyst with a racemic material can form two different diastereomeric complexes. Since the complexes are diastereomers, they have different properties different rates of formation, stabilities, and rates of reaction. The products form from the diastereomeric substrate-catalyst complexes at different rates. Therefore, a chiral catalyst is theoretically able to separate enantiomers by reacting with one enantiomer faster than the other. The catalysts used in kinetic resolutions are often enzymes. Enzymes are constructed from chiral amino acids and often differentiate between enantiomeric substrates. 

Analytical Properties Microcrystalline triacetylcellulose swells in organic solvents separation of racemic thioamides, sulfoxides, organophosphorus compounds, drugs, and amino acids derivatives separations of these racemates were achieved at pressures at or above 4.9 MPa Reference 10... 

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