Tyrosine, enantiomers

The experimental dichroism is seen to have its greatest magnitude some 5 eV above threshold, where 0.10. This corresponds to an asymmetry factor in the forward-backward scattering of y 20%. Such a pronounced PECD asymmetry from a randomly oriented sample looks to comprehensively better the amazingly high 10% chiral asymmetry recorded with highly ordered nanocrystals of tyrosine enantiomer [25] or the spectacular 12.5% asymmetry reported from an oriented single crystal of a cobalt complex [28]. 

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). 

Although some applications for preparative-scale separations have already been reported [132] and the first commercial systems are being developed [137, 138], examples in the field of the resolution of enantiomers are still rare. The first preparative chiral separation published was performed with a CSP derived from (S -N-(3,5-dinitrobenzoyl)tyrosine covalently bonded to y-mercaptopropyl silica gel [21]. A productivity of 510 mg/h with an enantiomeric excess higher than 95% was achieved for 6 (Fig. 1-3). 

The improvements in resolution achieved in each deconvolution step are shown in Figure 3-3. While the initial library could only afford a modest separation of DNB-glutamic acid, the library with proline in position 4 also separated DNP derivatives of alanine and aspartic acid, and further improvement in both resolution and the number of separable racemates was observed for peptides with hydrophobic amino acid residues in position 3. However, the most dramatic improvement and best selectivity were found for c(Arg-Lys-Tyr-Pro-Tyr-(3-Ala) (Scheme 3-2a) with the tyrosine residue at position 5 with a resolution factor as high as 28 observed for the separation of DNP-glutamic acid enantiomers. 

The enantiomeric purity of protected amino acids used in peptide synthesis can be determined by pre-column partial deprotection followed by derivatization with Marfey s reagent (116). The Marfey diastereoisomers can be easily resolved and determined by RP-HPLC using an ODS-Hypersil column288. Fifteen amino acids collected from mammalian tissues were derivatized with Marfey s reagent and subjected to two-dimensional TLC. Each individual spot (enantiomeric mixture of a diasteroisomer) was then resolved by RP-HPLC. Except for tyrosine (46) and histidine (117), subnanomole quantities of enantiomers could be analyzed289,290. 

A 5-(methylthio)methyl-substituted derivative (cis-28) of ( + )-3-PPP has been reported [91]. The background to the study was the structural similarity between pergolide (29) and (cis-28). However, the biological testing of (cis-28) showed that it is inactive in vivo (GBL model), while an in vitro assay (inhibition of tyrosine hydroxylation) showed (cis-28) to be equipotent to racemic 3-PPP itself. These results indicate that the steric bulk in (cis-28) is not compatible with potent DA receptor interaction. However, since compound (cis-28) was not resolved, there is a possibility that one or both of the enantiomers of (cis-28) might have antagonistic properties [89]. 

A number of variations on this type of coating have been prepared and offer some improvement over the original phase. Figure 11.11 shows the volatile pentafluoropropionamide-trifluoroethyl ester (PFP-TFE) derivatives of L and D phenylalanine. Figure 11.12 shows the separation of PFP-TFE derivatives of the D and L enantiomers of the amino acids phenylalanine and p-tyrosine on a Chirasil Val column, the D(/ )-enantiomers elute first. Chirasil Val generally performs best for the separation of enantiomers of amino acids, for many other compounds it is not as effective. 

For resolution of the racemate 12 two different procedures can be applied 124 the en-antioselective enzymatic deacylation of chloroacetyl-DL-a-aminosuberic acid at pH 7.2 with Taka-acylase or the enantioselective salt precipitation of Z-dl-Asu-OH with D-tyrosine hydrazide according to the method of Vogler et alJ25 Complete enzymatic digestion is achieved in about ten days at 37 °C, and the optically pure L-enantiomer is obtained in 80% yield but the overall efficiency is lower than that of the chemical method. Fractional crystallization affords in good yields the Z-l-Asu-OH derivative 13 which is then used directly as a suitably protected intermediate in subsequent derivatization steps (see Scheme 6). Moreover, the recovery of the D-enantiomer from the mother liquors is also easy in this case. 

Figure 2.6 By resolution of df-amino acid esters under conditions of dynamic resolution 100% of a single enantiomer may be produced. Using catalytic amounts of pyiidoxyl-5-phosphate, which forms a Schiff s base with the ester and not the acid, the unreacted D-ester may be racemised in situ and for instance L-tyrosin has been obtained in 97% ee and 95% yield.

The Z-protected derivative, again prepared by standard methods using benzyl chloroformate,t208 may serve in the case of racemic pipecolic acid for resolution into the pure enantiomers by fractional crystallization with L-tyrosine hydrazide/208 Acylation with N-protected pipecolic acid or of pipecolyl peptides is performed by standard procedures via the active ester methods, e.g. A-hydroxysuccinimide ester/121 by the mixed anhydride method, e.g. with isobutyl chloro-formate 95-114 or pivalic acid chloride/121 as well as by DCC/HOBt/118 In the synthesis on solid support, longer coupling times are required when compared to N-protected proline.1[235 ... 

Although in principle naturally occurring (—)-galanthamine could have been prepared by an identical sequence of reactions commencing with D-tyrosine, an alternate route to 319, the enantiomer of 314, was developed. Thus, epimeriza-tion of the methyl ester group at C-6 of the A -trifluoroacetamide derived from 315 followed by oxidation of the allylic alcohol with pyridinium chlorochromate furnished 319 in 78% optical purity, albeit in low chemical yield. Since 319 could be converted to (-)-galanthamine (291) by the same sequence of reactions outlined for the transformation of 314 to (+)-galanthamine, its preparation may be considered to represent a formal total synthesis of 291 from L-tyrosine (163). 

The favorable effect of the enamide function on asymmetric induction is indicated not only by the result with compound I, but also by later results summarized in Table I, where optical purities in the range of 70 to 80% were generally obtained for various derivatives of alanine, phenylalanine, tyrosine, and 3,4-dihydroxyphenylalanine (DOPA). The Paris group found that the Rh-(-)-DIOP catalyst yielded the unnatural R or d -amino acid derivatives, whereas l-amino acid derivatives could be obtained with a (+)-DIOP catalyst. Since the optical purity of the IV-acylamino acids can often be considerably increased by a single recrystallization (fractionation of pure enantiomer from racemate) and the IV-acetyl group can be removed by acid hydrolysis, this scheme provides an excellent asymmetric synthesis route to several amino acids. 

The carbanion257197 was prepared by reacting at -20 °C LDA in situ with the ester 198. d- and L-enantiomers of 14C-labelled tyrosine have been separated by a Daicel Chiralpak WH column258. The enantiomeric purity of isolated L-isomer of 196 was 99%, the radiochemical purity was 99%, and the r.y. was 24%, with a specific radioactivity of 55 mCi mmol-1. 

There is at the moment no compelling evidence for either of these mechanisms. An important experiment which needs to be done with enzymes of this class is to probe for internal transfer of the a-hydrogen from one enantiomer to the other under single turnover conditions with trapping of the product. An experimental design to accomplish this is currently being explored with tyrosine phenol-lyase and will be discussed below. Demonstration of any internal return of the a-hydrogen... 

Figure 4.6-13 Optical rotation q recorded as outlined in Fig. 4.6-12 Spectra of two differently concentrated solutions of S-tyrosine-methylester in the nematic mixture EBBA/MBBA (equimolar mixture of N-(p-ethoxybenzylidene)-p - -butylaniline and its methoxy analogue 2 of Table 4.6-1 Riedel-de Haen), left RCE (molar fraction x fa 0.024) related to the selective reflection band indicating pitch and handedness of the. structure, thus characterizing the chirality of the solute molecules by the helical twisting power right Sequence of ACE (,v se 0.0024, therefore the RCE should occur around 200 cm ) each of which indicates the induced handedness and therefore, discriminates enantiomers (Koite, 1978).

Introduction. L-iyrosine hydrazide (L-Tyr-NHNH2) (1) is useful in the resolution of simple carboxylic acids and amino acid derivatives. It often forms highly crystalline salts with these compounds, which yield diastereomerically pure salts in just one or two recrystallizations. The yields of resolved acids tend to be high, and in many cases both enantiomers can be obtained from the same operation (the more soluble diasteromeric salt that remains in the mother liquors is often quite pure). The tyrosine hydrazide can be recovered without appreciable loss of optical activity. 

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