Leucine enantiomers

Probl6m 28.10 Write out a stepwise sequence that shows how a racemic mixture of leucine enantiomers can be resolved into optically active amino acids using (R)-a-methylbenzylamine. 

In another approach, reactive monodisperse porous poly(chloromethylstyrene-co-styrene-co-divinylbenzene) beads have been employed for the preparation of chiral HPLC packings. Thus, reactive chloromethyl groups were derivatized to yield amino functionalized beads onto which both rt-basic and rt-acidic type chiral. selectors, (/ )- -(l-naphthyl)ethylamine and (/ )-A -(3.5-dinitrobenzoyl)phenylglycine, respectively, were attached. The resulting chiral particles were chromatographically tested for the enantioseparation of model SAs. Despite the presence of strongly competitive it-TT-binding sites of the styrenic support these chirally modified beads afforded baseline separations for 2,2,2-trifluoro-l-(9-anthryl) ethanol and Af-(3.5-dinitro-benzoyl) leucine enantiomers, respectively [369. ... 

The preparative capability of the present system is demonstrated in the separation of DNB-leucine enantiomers by varying the CS concentration in the stationary phase. The sample loading capacity is found to be determined mainly by the CS concentration or total amount of CS in the stationary phase that is, the higher the CS concentration in the stationary phase, the greater the peak resolution and sample loading capacity. Consequently, the standard HSCCC column can be used for both analytical and preparative separations simply by adjusting the amount of CS in the stationary phase. 

Bormer W.A., Van Dort M.A. and Flores J.J. (1974) Quantitative gas chromatographic analysis of leucine enantiomers. A comparative study. 

Fig. 5 Incorrect use of the three-point interaction model seen in [9]. Interaction of methyl-Af-(2-naphthyI)aIaninate with the chiral selector Ai-fS.S-dinitrobenzoyli-f i-leucine n-propylamide. Switching Hydrogen 15 and Group 18 on the selector asymmetric center ( ) would produce the other enantiomeric form. Switching hydrogen 9 and methyl 10 of the leucine asymmetric center ( ) would make the (R)-leucine enantiomer. In both cases, the three interactions mentioned would be similarly possible not allowing for any chiral discrimination...

Remelli et al. [10] proposed a new chiral selector, L-A-decylhistidine (LNDH), prepared through selective alkylation with 1-iododecane of L-histidine at the pyrrolic nitrogen atom of the heterocyclic ring (see Figure 5.If). As shown in Table 5.3, the copper (II) complex of this chiral selector exhibited a high selectivity toward several enantiomers of aromatic amino acids, while no significant separation was observed for DL-valine, DL-alanine, and DL-leucine enantiomers. With respect to the behavior of aromatic amino acids, the D-enantiomer was the most... 

The amino acids L-leucine, T-phenylalanine, L-tyrosine, and L-tryptophan all taste bitter, whereas their D-enantiomers taste sweet (5) (see Amino ACIDS). D-Penicillamine [52-67-5] a chelating agent used to remove heavy metals from the body, is a relatively nontoxic dmg effective in the treatment of rheumatoid arthritis, but T.-penicillamine [1113-41 -3] produces optic atrophy and subsequent blindness (6). T.-Penicillamine is roughly eight times more mutagenic than its enantiomer. Such enantioselective mutagenicity is likely due to differences in renal metaboHsm (7). (R)-ThaHdomide (3) is a sedative—hypnotic (3)-thaHdomide (4) is a teratogen (8). 

Fig. 3-1. Separation of racemic 3,5-dinitrobenzamido leucine Al.A -diallylamide on silica and polymer-based chiral stationary phases. Conditions column size 150 x 4.6 mm i.d. mobile phase 20 % hexane in dichloromethane flowrate 1 mL min injection 7 pg. Peaks shown are l,3,5-tri-rert.-butylbenzene (1), R-enantiomer (2) 5-enantiomer (2 ). (Reprinted with permission from ref. [8]. Copyright 1997 American Chemical Society.)...

A simple and rapid method of separating optical isomers of amino acids on a reversed-phase plate, without using impregnated plates or a chiral mobile phase, was described by Nagata et al. [27]. Amino acids were derivatized with /-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA or Marfey s reagent). Each FDAA amino acid can be separated from the others by two-dimensional elution. Separation of L- and D-serine was achieved with 30% of acetonitrile solvent. The enantiomers of threonine, proline, and alanine were separated with 35% of acetonitrile solvent and those of methionine, valine, phenylalanine, and leucine with 40% of acetonitrile solvent. The spots were scraped off the plate after the... 

Figure 24 shows the ternary phase diagram (solubility isotherm) of an unsolvated conglomerate that consists of physical mixtures of the two enantiomers that are capable of forming a racemic eutectic mixture. It corresponds to an isothermal (horizontal) cross section of the three-dimensional diagram shown in Fig. 21. Examples include A-acetyl-leucine in acetone, adrenaline in water, and methadone in water (each at 25°C) [141].

Micelle-forming copper complexes were found to effectively discriminate between enantiomers in the hydrolysis of a-amino esters (257). Hydrolysis of (.V)-phenylalanine p-nitrophenyl ester is 14-fold faster than its enantiomer, Eq. 223. Leucine affords 10-fold faster hydrolysis. The authors note that the micellar nature of these systems is extremely important for both rate of hydrolysis and selectivity (258). For example, the /V-mcthyl-dcrivcd ligand 419b leads to inhibition of the hydrolysis process, relative to catalysis by Cu(II) ion alone. 

Their studies involved the partial polymerization of NCAs of mixtures of specific amino adds having known e.e.s, followed by determination of the e.e.s of the amino adds in both the resulting polypeptides and in the residual unreacted NCA monomers. [94] In a typical experiment it was found that when an optically impure leucine NCA monomer having an l > d e.e. of 31.2% was polymerized to the extent of 52 % to the helical polyleucine peptide, the e.e. of the polymer was enhanced to 45.4 %, an increase of 14.2 %. In the same experiment the e.e. of the unreacted leucine NCA monomer was depleted to a similar extent. Analogous experiments with valine NCAs of known e.e.s, however, led to a reverse effect, namely, the preferential incorporation of the racemate rather than one enantiomer into the growing polyvaline peptide. This finding was interpreted to be the result of the fact that polyvaline consists of (3-sheets rather than a-helices, emphasizing that the Wald mechanism applies only to a-helix polymers. At about the same time Brach and Spach [95] showed that, under proper conditions, (3-sheet polymers could also be implicated in the amplification of amino add e.e.s. 

ESl-MS of cysteine solutions yields only the singly protonated hexamer [(Cys)6-H]. No preference for the chirality of the individual aminoacidic components is observed." Addition of cysteine to a serine solution yields abundant homochiral mixed octamer [(L-Ser)g m(L-Cys) -H] (m = 0-2). No [(L-Ser)g. (D-Cys)m H]+ (m = 1,2) octamers, but only [(L-Ser)g-H]+ are observed by using the wrong D-cysteine enantiomer. A similar picture is observed by replacing cysteine with other aminoacid, such as aspartic acid, asparagine, leucine, and methionine. 

To illustrate this beneficial effect of the carbamate-binding increment. Figure 1.10 compares the separation of A/-(3,5-dinitrobenzoyl)leucine (DNB-Leu) enantiomers... 

Ultrapurification of 50 mmolL DNB-D,L-Leucine in a Cascade of Five Stages with Two Modules and Two Enantiomeric Carrier (Quinine and Quinidine Derivative with 5 vol% Polysiloxane-supported Carrier) Transmembrane Material Stream J, Enantioselectivity a, Enantiomer Excess ee, Purity, and Yield of DNB-D-Leucine... 

In a similar fashion to those results obtained for the oxidation process, on switching from poly-(L)-leucine to poly-(D)-leucine the opposite configuration of the polyether was observed (absolute configuration of products unknown). Unexpected, however, was the observation that poly-(L)-phenylalanine furnished the opposite enantiomer to that observed employing poly-(L)-leucine. Thus, it has been shown that addition of nucleophiles other than peroxide anion can be catalysed by polyamino acids with significant stereocontrol [22]. 

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