Corresponding alanines

In an early example, commercial bacitracin ( ), a cyclic antibiotic (the structure of bacitracin F is given) was found to hydrolyze L-(P) about twice as fast as the d-enantiomer. No selectivity was found for the corresponding alanine enantiomers. Most likely an imidazole group from histidine is involved in the hydrolysis, but owing to the structural complexity of the peptide it is not possible to determine the origin of the enantioselectivity. 

Previously, Ascic et al. [43] reported the same reaction with the Hoveyda-Grubbs II catalyst and trifluoroacetic acid as a bicatalytic system, but as a racemic version [43]. The intermediate acyliminium ion readily attacks also other tethered nucleophiles, such as trimethoxybenzene, benzothiophene, thiophene, 0,0-dimethyl catechol, and furan, intramolecularly. When tryptophane or the corresponding alanine derivatives are employed, reasonable levels of diastere-oselectivity can be observed for the terminal Pictet-Spengler acyhminium cyclization. Even a tethered alcohol functionahty diastereoselectively traps the chiral acyhminium intermediate, furnishing bicychc OAf-acetals. 

During the study on enantioselective organocatalytic reductive amination, MacMillan et al. found that the pyruvic acid-derived cyclic imino ester could be efficiently reduced to yield the corresponding alanine amino ester with 97% ee and 82% yield... 

Most syntheses of iminocarboxylic acid derivatives start from a-keto acids or a-amino acids. Thus Appel and Hauss 12) described the formation of a-iminopropionic acid ester by treatment of pyruvic acid ester with triphenylphosphine imine. This product was however not isolated, but hydrogenated directly to the corresponding alanine ester. 

Pig. 9. Mean total energy vs. At for the Verlet (a = 0), IM (a = 1/4) and LIM2 (fv = 1/2) schemes for the blocked alanine model. The three lines correspond to averaging energies over an increasing number of steps 2 x 10 (dotted line), 6 x 10 (dashed line), and 10 (solid line). 

FIGURE 27 3 Application of electrophoresis to the separation of aspartic acid alanine and lysine according to their charge type at a pH corresponding to the isoelectric point (pi) of alanine... 

There are thousands of breweries worldwide. However, the number of companies using fermentation to produce therapeutic substances and/or fine chemicals number well over 150, and those that grow microorganisms for food and feed number nearly 100. Lists of representative fermentation products produced commercially and the corresponding companies are available (1). Numerous other companies practice fermentation in some small capacity because it is often the only route to synthesize biochemical intermediates, enzymes, and many fine chemicals used in minor quantities. The large volume of L-phenylalanine is mainly used in the manufacture of the artificial dipeptide sweetener known as aspartame [22389-47-0]. Prior to the early 1980s there was httle demand for L-phenyl alanine, most of which was obtained by extraction from human hair and other nonmicrobiological sources. 

Enzymatic Process. Chemically synthesized substrates can be converted to the corresponding amino acids by the catalytic action of an enzyme or the microbial cells as an enzyme source, t - Alanine production from L-aspartic acid, L-aspartic acid production from fumaric acid, L-cysteine production from DL-2-aminothiazoline-4-catboxyhc acid, D-phenylglycine (and D-/> -hydtoxyphenylglycine) production from DL-phenyUiydantoin (and DL-/)-hydroxyphenylhydantoin), and L-tryptophan production from indole and DL-serine have been in operation as commercial processes. Some of the other processes shown in Table 10 are at a technical level high enough to be useful for commercial production (24). Representative chemical reactions used ia the enzymatic process are shown ia Figure 6. 

In principle, energy landscapes are characterized by their local minima, which correspond to locally stable confonnations, and by the transition regions (barriers) that connect the minima. In small systems, which have only a few minima, it is possible to use a direct approach to identify all the local minima and thus to describe the entire potential energy surface. Such is the case for small reactive systems [9] and for the alanine dipeptide, which has only two significant degrees of freedom [50,51]. The direct approach becomes impractical, however, for larger systems with many degrees of freedom that are characterized by a multitude of local minima. 

Each leg of the titration curve is calculated separately. The first leg, from pH 1 to 6, corresponds to the dissociation of protonated alanine, H2A+. The second leg, from pH 6 to 11, corresponds to the dissociation of zwitterionic alanine, HA. It s as if we started with H2A+ at low pH and then titrated with NaOH. When 0.5 equivalent of NaOH is added, the deprotonation of H2A+ is 50% done when 1.0 equivalent of NaOH is added, the deprotonation of H2A+ is complete and HA predominates when 1.5 equivalent of NaOH is added, the deprotonation of H A is 50% done and when 2.0 equivalents of NaOH is added, the deprotonation of HA is complete. 

Figure A8.18 A racemic mixture of a-hydroxyacids (like L, D-lactate) can be transformed via the corresponding a-ketoacid (pyruvate) to the desired L-amino acid (L-alanine) with cofactor recycling.

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... 

No compound other than the methyl ester of N-benzoyl-Lphenylalanine, 33, is an obvious choice for an open-chain analog of the locked substrate 25 but D-24, on the other hand, may be a locked analog of either N-benzoyl-D-alanine methyl ester 34 or of N-formyl-D-phenylalanine methyl ester 35 (75). If 24 is an analog of 34 rather than 35, the comparison of the two locked analogs made in Section V.B. is not valid the phenyl of 24 would then correspond to the benzoyl phenyl of 34. 

The third reason for favoring a non-radical pathway is based on studies of a mutant version of the CFeSP. This mutant was generated by changing a cysteine residue to an alanine, which converts the 4Fe-4S cluster of the CFeSP into a 3Fe-4S cluster (14). This mutation causes the redox potential of the 3Fe-4S cluster to increase by about 500 mV. The mutant is incapable of coupling the reduction of the cobalt center to the oxidation of CO by CODH. Correspondingly, it is unable to participate in acetate synthesis from CH3-H4 folate, CO, and CoA unless chemical reductants are present. If mechanism 3 (discussed earlier) is correct, then the methyl transfer from the methylated corrinoid protein to CODH should be crippled. However, this reaction occurred at equal rates with the wild-type protein and the CFeSP variant. We feel that this result rules out the possibility of a radical methyl transfer mechanics and offers strong support for mechanism 1. 

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