Configuration of amino acids

The absolute configurations of amino acids 198a (the racemic counterpart was designated 186c) and 198i on the basis of X-ray crystal structure analysis data of the a-azido esters 197a-Me and 197i-Bn were (R) and (S,S,S), respectively. 

Differences of <5 = 0.32-0.40 in the, 9F chemical shift for epimeric A -acylated Mosher derivatives of aliphatic a-amino acids, in particular alanine, as well as its amides and peptide derivatives, are sufficiently large to serve as a racemisation test23. However, high-field spectrometers are recommended to provide improved sensitivity (<0.5%). Table 19, representing analysis data taken at 376.5 MHz, can be found in Section 3.2.2.9. Analysis of absolute configuration of amino acids and amines can be more accurate using a modified Mosher method24. 

It has been reported that a variety of single-chain amphiphiies spontaneously produce stable, membrane-forming aggregates when dispersed in water 258 260). Dialky 1-amphiphile l-III (l or d means l- or D-configuration of amino acid unit in compound III, respectively), which was prepared by condensation of didodecyl L-glutamate and p-(4-bromobutoxy)benzoic acid and the subsequent quarterization with tri-methylamine, produces bilayer vesicles in water as probed by electron microscopy 251 >. 

Figure 1.4 The D/L configurations of amino acids. Note that the carboxylic acid group must be drawn at the top and the R group at the bottom of the Fischer projection. Stereogenetic centres in the R group do not affect the D/L assignment...

Thus, we have developed a method for the detection of the absolute configuration of amino acids with low enantioenrichment. We thought that the absolute configuration of amino acids can be determined by detecting the absolute configuration of the produced pyrimidyl alkanol with high enantiomeric excess by asymmetric autocatalysis using amino acids as chiral initiators (Scheme 18). 

Whether the enantiomeric preference, such as found in the L-configuration of amino acids or the D-configuration of sugars, comes from a deterministic or a random process... 

Antibodies to one protein antigen will often react (cross-react) with a wide variety of similar proteins from other species. For example, 15% of the antibody in a polyclonal antiserum to bovine serum albumin will react with human serum albumin. The molecular basis for this cross-reaction is not clearly understood, but cross-reactivity is believed to be caused by the presence of a configuration of amino acid side chains on another protein molecule that has a sufficient overall similarity to the specific configuration on the original antigen that induced antibody formation. 

Unfortunately, the 3-phenyl-2-thiohydantoins formed in the Edman stepwise degradation suffer racemisation (Davies and Mohammed, 1984) so that the method cannot be used to determine the configuration of amino acids in a peptide. This is not usually a serious limitation, but enantiomerisation is a perpetual hazard in peptide synthesis (Chapter 7). It is therefore desirable to determine if enantiomerisation has occurred at any residue. Such information could be important, for example, in dating bone proteins obtained in archaeological excavations. Examination of the chiral purity of the amino acids in a total acid hydrolysate is not satisfactory. 

The chemistry of Rh(DIPAMP) and mechanism has been reviewed [9,14-16,19]. Marginally higher catalyst efficiencies are observed with higher alcohols compared with methanol, whereas the presence of water can result in the reduction of slurries. Filtration of the product can improve the %ee while the catalyst and D,L-product remain in the mother liquor. The catalyst stereoselectivities decreases as hydrogen pressure increases. [Rh(COD)(R,A-DIPAMP)] + BF4 (13) affords the -configuration of amino acids upon reduction of the cnamide substrate. Reduction of enamides in the presence of base eliminates the pressure variances on the stereoselectivities, but the rate of reaction under these conditions is slow [15]. 

An elegant method for determining the optical configuration of amino acids on paper chromatograms using the enzyme D-amino acid oxidase has been described by Synge (1949). 

Chiroptical methods (ORD and CD spectroscopy) allow the direct determination of the absolute configuration of amino acids to be made, especially with modern commercial spectrometers, which provide wavelength scales down to 180 nm. The chiroptical properties of a-amino acids have been widely studied (Djerassi, 1960, pp. 201-228 Strem et a/., 1961 Dirkx and Sixma, 1964 Gaffield, 1964 lizuka and Yang, 1964 Crabbe, 1965, pp. 304-316,1971, 1972, pp. 54-58 Jennings et al, 1965a Legrand and Viennet, 1965, 1966 ... 

Whereas the older literature is concerned mainly with the correlation of chiroptical data with the absolute configuration of amino acids, most of the more recent studies attempt to deal with conformational phenomena as well. Thus, the conformations of the aromatic amino acids D-phenylglycine... 

ORD spectra and the configuration of amino acids indicated by an extremum around 530 nm. The only exception was the copper complex of L-(—)-proline, the entire curve of which is shifted hyposochromically. 

In this chapter, we have attempted to assess the usefulness of chiroptical techniques for determining the absolute configuration of amino acids and small peptides, either directly or via their chromophoric derivatives. Several empirical and semiempirical rules have been described. The importance of conformational equilibria has been stressed repeatedly, and solvent effects have been discussed. It should be emphasized once again that the widest possible variety of standards should be studied when an absolute configuration is to be assigned to an unknown on the basis of empirical chiroptical rules. 

Porphyrin tweezer 51 was used to determine the absolute configuration of chiral diamines by measuring the CD spectrum of the diamine-51 complex. - Upon com-plexation, the two porphyrins adopt a chiral configuration, which leads to a coupled CD. The absolute configuration of amino acids and amino alcohols can be similarly detennined after derivatization to diamines. Ji and coworkers also reported CD smdies of the binding of diamine to a zinc porphyrin dimer. ... 

The primary structure of a polypeptide chain is given by the number, type, sequence, and configuration of amino acid or imino acid residues joined together by peptide bonds. It thus gives the constitution of the polypeptide or protein. In writing the sequence, the N-terminal amino acid is always written on the left, the C-terminal amino acid is always written on the right. Thus, gly-ala-ser means... 

Compound Formula Plant species Plant family Character of isolate, comments Configuration of amino acid Ref. Occurrence of second constituent Chemical synthesis of derivative Ref. 

The alternative R,S convention is also used to specify the configurations of amino acids. According to this convention, L-alanine is designated (S)-alanine. Although the D,L method of designating the stereochemistry of amino add chiral centers is awkward, the historical use of this system is so deeply rooted in the scientific literature that it is still most commonly used when referring to amino adds as well as carbohydrates. We will therefore use the d,l convention throughout the remainder of this chapter. 

SS (RR, RS, or SR) refers to the absolute configurations of the nitrogens of the secondary amines these are fixed by the chelate ring conformations. The absolute configurations of amino acids are designated S (for L) or R (for D). 

The configuration of amino acids relative to that of D-glyceraldehyde has also been established. The work of Freudenberg and Kuhn which is based on a careful and circumscribed application.of the principle of optical superposition is reviewed and it is su ested that it is not by itself conclusive. A more decisive proof for the n configuration of amino acids is obtained from the X-ray structure of glucosamine and enzymic specificity. The configuration of secondary asymmetric centers in certain amino-acids is considered and it is concluded that the carboxyl and hydroxyl groups in hydroxy-proline are in trans position to each other. 

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