Alanine, chiral forms

Since the isolation of cathinone and the other khat phenylalkylamines from fresh material, and their structural and stereochemical characterization, there has been interest in producing these compounds synthetically in chiral form. Buckley and Rapoport (24) have shown that N-ethoxycarbonyl-L-alanine, as its acid chloride (10), can successfully acylate benzene in the presence of aluminum... 

It is also possible to convert nonchiral readily available industrial organic chemicals into valuable chiral natural-analogue products. This is demonstrated by the conversion of achiral fumaric acid to L(-)-malic acid with fumarase as the active enzyme. The same compound is converted to the amino acid L(-h)-aspartic acid by Escherichia bacteria that contain the enzyme aspartase. If pseudomonas bacteria are added, another amino acid L-alanine is formed (Eq. 9.10). 

Fig. 23 DL-Alanine mesocrystals formed in presence of a chiral double hydrophilic block copolymer, a SEM micrograph showing the facetted mesocrystals, b OL-Alanine single crystal control, c Higher resolution SEM of a mesocrystal surface showing the nanoparticle building units, d XRD pattern of a mesocrystal, and e of a single crystal. The figures were reproduced from [123] with kind permission of Wiley...

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Figure 17 shows the 11/A isotherms of racemic and enantiomeric films of the methyl esters of 7V-stearoyl-serine, -alanine, -tryptophan, and -tyrosine on clean water at 25°C. Although there appears to be little difference between the racemic and enantiomeric forms of the alanine surfactants, the N-stearoyl-tyrosine, -serine, and -tryptophan surfactants show clear enantiomeric discrimination in their WjA curves. This chiral molecular recognition is first evidenced in the lift-off areas of the curves for the racemic versus enantiomeric forms of the films (Table 2). As discussed previously, the lift-off area is the average molecular area at which a surface pressure above 0.1 dyn cm -1 is first registered. The packing order differences in these films, and hence their stereochemical differentiation, are apparently maintained throughout the compression/expansion cycles. 

The instability of these chiral monolayers may be a reflection of the relative stabilities of their bulk crystalline forms. When deposited on a clean water surface at 25°C, neither the racemic nor enantiomeric crystals of the tryptophan, tyrosine, or alanine methyl ester surfactants generate a detectable surface pressure, indicating that the most energetically favorable situation for the interfacial/crystal system is one in which the internal energy of the bulk crystal is lower than that of the film at the air-water interface. Only the racemic form of JV-stearoylserine methyl ester has a detectable equilibrium spreading pressure (2.6 0.3dyncm 1). Conversely, neither of its enantiomeric forms will spread spontaneously from the crystal at this temperature. 

Extractions of aqueous solutions of racemic amino-acid ester salts with solutions of / -6/s(dinaphthyl)-22-crown-6 [284] in chloroform revealed the dependence of the enantiomeric distribution constant on the structure of the amino acid ester (Table 64). In order to limit the concentrations of complex in the aqueous phase, inorganic salts were added. In the case of tyrosine, serine and alanine no extraction of salt was observed obviously these salts form very hydrophilic complexes. The highest degree of chiral recognition was found with [284] and p-hydroxyphenylglycine methyl ester hexafluorophosphate [A(AG°)... 

Chiral dialkyl amphiphiles [61] and [62], prepared from alanine and glutamic acid (Kunitake et al., 1979b), also form bilayer structures when dispersed in water. Chiral bilayers should be interesting because they provide... 

At this point it is impossible to guess the architecture of the active catalyst. The folding of 10-mers of leucine and alanine in organic solvents is clearly of critical importance, and studies are in progress to understand the preferred shapes. Obviously, in its active form the catalyst binds and activates peroxide anion and/or the electron-poor alkene near its chiral surface, perhaps in a chiral cavity, but the precise orientation of catalyst and reactants in the initial bondforming Michael reaction remains unsolved. 

Another acid amide bond (-CO-NH-) creates the compound for the next constituent, pantoinate. This compound contains a chiral center and can therefore appear in two enantiomeric forms (see p.8). In natural coenzyme A, only one of the two forms is found, the (R)-pantoinate. Human metabolism is not capable of producing pantoinate itself, and it therefore has to take up a compound of (1-alanine and pantoinate— pantothenate ( pantothenic acid )—in the form of a vitamin in food (see p.366). 

With the exception of alanine, all of the naturally occurring amino acids contain a chiral carbon adjacent to the amino acid grouping. All of these amino acids are of the 1 or L form, meaning they rotate light in a negative direction. The rules governing the specification of the absolute configuration are such that you can get both S and R forms of the amino acids. Thus L-phenylalanine is an S enantiomer while L-cysteine is an R enantiomer. 

Ru(PPh3)(H2O)j(SB "0 constimtes a series of complexes, made from RuClj(PPh3)3 and a chiral Schiff base SB obtained from salicylaldehyde and the L-forms of alanine, valine, serine, arginine, cysteine and aspartic acid. They were characterised by IR, circular dichroism, H and C[ H] NMR spectroscopies and by cyclic voltammetry. The supposed structure of one is shown in Fig. 1.41 [917]. 

Another approach employing chiral acyclic azomethine ylides was published in two recent papers by Alcaide et al. (85,86). The azomethine ylide-silver complex (51) was formed in situ by reaction of the formyl-substituted chiral azetidinone (50) with glycine (or alanine) in the presence of AgOTf and a base (Scheme 12.18). Azomethine ylides formed in this manner were subjected to reaction with various electron-deficient alkenes. One example of this is the reaction with nitrostyrene, as illustrated in Scheme 12.18 (86). The reaction is proposed to proceed via a two step tandem Michael-Henry process in which the products 52a and 52b are isolated in a... 

From Table 8 it is obvious that the resolution always increases with an increase of the number of benzene rings and that riboflavine is a more powerful selector than the nucleotides, but not as good as TAPA. An interesting experiment shows that it is not always necessary to have the selector coated or bound to the solid phase but that it can sometimes be used as well, dissolved in the mobile phase. The n-dodecyl ester of N-(2,4-dinitrophenyl)-L-alanine is able to discriminate between the enantiomers of l-aza-[6]-helicene, when used as a chiral dopant in the mobile phase in HPLC on a reversed phase column 93) (see Table 9). The usefulness of this dopant must be due to the known ability of a dinitrophenyl moiety to form CT-complexes with polycyclic aromatic hydrocarbons the presence of a chiral site near this group causes resolution of helicenes, because the steric interactions in diastereomeric complexes will be quite different. 

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