D, L-DOPA

M. Argentini, C. Wiese, R. Weinreich, Synthesis of 5-fluoro-D/L-DOPA and [F-18]5-fluoro-L-DOPA, J. Fluor. Chem. 68 (1994) 141-144. 

Gubitz, G., Jellenz, W., and Schonleber, D., High performance liquid chromatographic resolution of the optical isomers of D,L-tryptophane, D,L-5-hydroxytryptophan and D,L-dopa on cellulose columns, J. High Resolut. Chromatogr. Chromatogr. Commun., 3, 31, 1980. 

Cellulose was the first sorbent for which the resolution of racemic amino acids was demonstrated [23]. From this beginning, derivatives such as microcrystalline triacetylcellulose and /3-cyclodextrin bonded to silica were developed. The most popular sorbent for the control of optical purity is a reversed-phase silica gel impregnated with a chiral selector (a proline derivative) and copper (II) ions. Separations are possible if the analytes of interest form chelate complexes with the copper ions such as D,L-Dopa and D.L-penicillamine [24], Silica gel has also been impregnated with (-) brucine for resolving enantiomeric mixtures of amino acids [25] and a number of amino alcohol adrenergic blockers were resolved with another chiral selector [26]. A worthwhile review on enantiomer separations by TLC has been published [27],... 

Proof of enantiomeric purity is necessary in the case of L-3,4-dihydroxyphenylalanine (L-DOPA), a drug used to treat Parkinson s disease, because of the high toxidty of the D enantiomer. Previously, D,L-DOPA was resolved by Frank, Nicholson, and Bayer using Chirasil-val (41). Figure 6 shows the separation of D, L-DOPA on a column with per-pentylated ot-cydodextrin. In the case of a-methyl-DOPA (Aldomet) [4], a drug that is used in its L form for its antihypertensive activity, the enan-... 

C. Wiese and co-workers have synthesized 5-fluoro-D/L-dopa and the corresponding [ F]5-Fluoro-L-dopa starting from 5-nitrovanillin via malonic ester synthesis, the Balz-Schiemann reaction, and the separation of the racemic mixture [ F]5-fluoro-D/L-dopa utilizing a chiral FIPLC system. The inactive 5-fluoro-D/L-dopa was obtained in an eight-step synthesis with an overall yield of 10%. 

Argentini, M., Wiese, C., Weinreich, R. Syntheses of 5-fluoro-D/L-dopa and [18F]5-fluoro-L-dopa. J. Fluorine Chem. 1994, 68,141-144. 

No direct electron transfer between melanin particles suspended in aqueous buffers and electrodes has been observed. This allowed the use of the polarographic method in monitoring the concentration changes of TF and Fe mediators reacting with d,L-dopa melanin (.210). Moreover,... 

Experiments were carried out using the D-/L-DOPA (P-(3,4-dihydroxyphenyl) alanine) system with organic acids as the solvents and organic aldehydes as the catalysts for the racemization reaction. Under adequate conditions empirically determined, three rate processes of preferential crystallization, racemization reaction and solvent evaporation proceeded simultaneously at the same rate and the solution composition would then be kept unvaried at the same one as that of initial mixture as shown Figure 14. This process is therefore possible to operate continuously by feeding a conglomerate mixture and by removing the product crystals and the solvents. 

The naturally occurring amino acid L-3,4-dihydroxyphenylalanine (L-dopa) was first synthesized as D,L-racemate. D,L-dopa exerted significant effects on glucose metabolism and arterial blood pressure. It has also been found to be effective against Parkinson s disease. 

Figure 1 Remission-location curves (a) D,L-dopa (b) D,L-tryptophan (c) D,L-S-hydroxytryplophan.

This work, some aspects of which are outlined below, has served to show that melanins are in fact highly irregular polymers in which several different types of monomer unit are linked in a variety of ways. From the results of an extensive series of experiments in which D L-dopa deuteriated separately at the 1, 2, 2, 5 and 6 positions and D L-l-[ C]-dopa were converted into dopa-melanin autoxid-atively or by enzymic oxidation in the presence of mushroom polyphenol oxidase. Swan and his collaborators have conclude that the principal structural fragments in the polymer are probably (0 uncyclised units of dopa (68, 0.1), (ii) indoline carboxylic acid units (69, 0.1), ( /) indole units (70, 0.65) and (iv) pyrrole carboxylic acid units (71, 0.15). The indoline (69) and indole (70) units are presumed to exist in the polymer half in the phenolic and half in the quinonoid forms. It was also suggested that the pyrrole carboxylic unit (71) is probably derived by oxidative fission, during the synthesis of the dopa-melanin, of a benzenoid unit such as (70). 

FIGURE 3.3 Separation of D,L-dopa on Chiralplate. Zones (1) L-dopa, (2) D,L-dopa, (3) D-dopa, (4) 3% L-dopa in D-dopa, and (5) 3% D-dopa in L-dopa. (Reprinted from the Machery-Nagel Application Database. With permission.)... 

The following chiral reagents were employed for diastereomer formation before sample application and chromatography on silica gel or silica gel G TLC plates (L)-leucine Af-carboxyanhydride for D,L-dopa-carboxyl- " C separated with ethyl acetate/formic acid/water (60 5 35) mobile phase and detected by ninhydrin [7 f 0.38 (d)/0.56 (l)] [43] Af-trifluoroacetyl-L-prolyl chloride for D,L-amphetamine separated with chloroform/methanol (197 3) and detected by sulfuric acid/formaldehyde (10 1) (Rf 0.49 (d)/0.55 (l)) [44] Af-benzyloxycarbonyl-L-prolyl chloride for D,L-methamphetamine separated with n-hexane/ethyl acetate/acetonitrile/diisopropyl ether (2 2 2 1) and detected by sulfuric acid/formaldehyde (10 1) [/ f 0.57 (l)/0.61 (d)] [44] (l/ ,2/ )-(-)-l-(4-nitrophenyl)-2-amino-1,3-propanediol (levobase) and its enantiomer dextrobase for chiral carboxylic acids separated with chloroform/ethanol/acetic acid (9 1 0.5) and detected under UV (254 nm) light R[ values 0.63 and 0.53 for 5- and / -naproxen, respectively) [45] (5)-(4-)-a-methoxyphenylacetic acid for R,S-ethyl-4-(dimethylamino)-3-hydroxybutanoate (carnitine precursor) with diethyl ether mobile phase [/ f 0.55 R)/0J9 (5)] [46] and (5)-(4-)-benoxaprofen chloride with toluene/acetone (100 10, ammonia atmosphere) mobile phase and fluorescence visualization (Zeiss KM 3 densitometer 313 nm excitation, 365 nm emission) (respective R values of R- and 5-isomers of metoprolol, oxprenolol, and propranolol were 0.24/0.28, 0.32/0.38, and 0.32/0.39) [47]. 

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