Fast enzymatic preparation of L-dopa from tyrosine and molecular oxygen: a potential method for preparing [15O]L-dopa (original) (raw)
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An Improved Synthesis of Selectively Protected l -Dopa Derivatives from l -Tyrosine
The Journal of Organic Chemistry, 2000
Many biologically active natural products such as the piperazinomycin (2), 1 K-13 (3a), 2 OF4949-I-IV (3b-e), 3 bouvardin and deoxybouvardin, 4 and RA-I-IV 5 contain a key structural unit isodityrosine (1) which is a naturally occurring dimeric form of L-Dopa [L-3-(3,4-dihydroxyphenyl)alanine, 4]. L-Dopa derivatives with two differentiated
International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes, 1990
The direct electrophilic radiofluorination of m-tyrosine using [18F]acetylhypofluorite was investigated. Results showed that this reaction was both rapid and efficient with recovered decay corrected yield of 71% radiofluorinated m-tyrosines based on starting [18F]acetylhypofluorite. Specific activity of the product obtained in this study was 100-200 mCi/mmol although 1-5 Ci/mmol are easily achievable with our improved production of [18F]AcOF. Three positional isomers were found and identified by 19F-NMR to be 2-, 4-, 6-fluoro-m-tyrosine with a distribution of 36:11:52, respectively. This measured distribution allowed the assignment of the radio-HPLC peaks. Biological studies are currently underway in our laboratory using these fluoro-m-tyrosines to determine which isomer would be most suited for the evaluation of the dopamine system by positron tomography.
Synthesis of no-carrier-added 6-[C-11]methyl-L-DOPA
2012
A simple and efficient synthesis of 3,4-dihydroxy-6-[C]methyl-L-phenylalanine ([C]MeDOPA) is described by use of Stille cross-coupling reaction between the corresponding tin precursor and [C]CH3I. The reaction conditions were determined with respect to reaction time and temperature. The best radiochemical yields were obtained at a temperature of 60 C and a reaction time of 5 min. Deprotection of the C-labeled intermediate was carried out by using 9 M HCl at 140 C for 10 min to afford 6-[C]methyl-L-DOPA. The overall yield was 63 ± 2.7% with a radiochemical purity[99%. The overall preparation time including hydrolysis, HPLC purification and formulation was 40 min. For reference, 6-methyl-D,L-DOPA was prepared in a four step synthesis and analytically characterized. As a new C-labeled amino acid, [C]MeDOPA exhibits an important alternative to [F]FDOPA for PET studies of tumors such as the neuroendocrine ones.
l DOPA production by immobilized tyrosinase
Applied Biochemistry and Biotechnology, 2000
The production of l-DOPA using l-tyrosine as substrate, the enzyme tyrosinase (EC 1.14.18.1) as biocatalyst, and l-ascorbate as reducing agent for the o-quinones produced by the enzymatic oxidation of the substrates was studied. Tyrosinase immobilization was investigated on different supports and chemical agents: chitin flakes activated with hexamethylenediamine and glutaraldehyde as crosslinking agent, chitosan gel beads, chitosan gel beads in the presence of glutaraldehyde, chitosan gel beads in the presence of polyvinyl pyrrolidone, and chitosan flakes using glutaraldehyde as crosslinking agent. The last support was considered the best using as performance indexes the following set of immobilization parameters: efficiency (90.52%), yield (11.65%), retention (12.87%), and instability factor (0.00). The conditions of immobilization on chitosan flakes were optimized using a two-level full factorial experimental design. The independent variables were enzyme-support contact time (t), glutaraldehyde concentration (G), and the amount of enzyme units initially offered (U C). The response variable was the total units of enzymatic activity shown by the immobilized enzyme (U IMO). The optimal conditions were t=24 h, G=2% (v/v), and U C=163.7 U. Under these conditions the total units of enzymatic activity shown by the immobilized enzyme (U IMO) was 23.3 U and the rate of l-DOPA production rate was 53.97 mg/(L·h).
Biological sources of L-DOPA: An alternative approach
Advances in Parkinson's Disease, 2013
Parkinson's disease was first formally identified by British physician James Parkinson in 1817 as "The Shaking Palsy". L-DOPA (3,4-dihydroxyphenyl-L-alanine) has been considered as a gold-standard treatment for Parkinson's disease. The world market for L-DOPA is about 250 t/year and the total market volume is about $101 billion per year. The present review summarizes the different biological sources for the production of L-DOPA. The process for L-DOPA production from different biological sources has advantages over the chemical methods such as, enantiometrically pure L-DOPA, less incubation time and cost effective method. L-DOPA is found naturally in certain plant foods, particularly broad beans which found to replenish brain levels of L-DOPA even more quickly, and for longer periods, than conventional medication.
Routine synthesis of carbon-11-carboxyl-labeled L-dopa
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1987
Carbon-11-carboxyl-labeled L-dopa has been synthesized by the modified Bucherer-Strecker method. The reaction mixture was first purified by chiral HPLC followed by deprotection using hydriodic acid. The entire procedure was performed in a remotely operated system which gave the product in 28% radiochemical yield (decay corrected) in an overall synthesis time of 55-60 min.
Journal of Chromatography A, 1980
Recent studies on the biosynthesis of catecholamines in the nervous system and chromafEn cells of the adrenal medulla have called for a sensitive assay of tyrosine 3-monooxygenase (tyrosine hydroxylase, E.C. 1.14.16.2) activity, i.e., the first and probably rate-limiting step of the pathway [for a review, see ref. 11. Radiochemical methods, using either 14C-or 3H-labelled L-tyrosine as the substrate, have generally been considered the most accura69, but high-performance liquid chromatography (HPLC) with electrochemical detection has more recently been found convenient for the assay of dihydroxyphenylalanine (DOPA)3*4_ Owing to the inherent problems of lifetime and maintenance of the electrochemical detectofl, we have based our detection of biogenic amines on measurement of their native fluorescence using a sensitive spectrofluorimeter equipped with a 20-~1 flow-through ceWg_ Although the native fluorescence of DOPA has generally been considered too weak for the assay of tyrosine 3-monooxygenase activity in biological materiallO, we have found it very useful in combination with HPLC. In the present study it is shown that the assay of DOPA by HPLC and fluorescence detection gives a sensitivity comparable to that of the electrochemical detecto9p4 and, owing to its simpler experimental approach, our method can more easily be applied to automated analyses to meet the special requirements of multiple analyses. Further, the method requires no particular maintenance, as is the case with the electrochemical detector. Finally, the published HPLC procedures for the assay of tyrosine hydroxylase activity have been found to be unsatisfactory in one or more of the following respects: (1) the procedures are laborious and time consuming; (2) they cannot be applied to crude biological materials owing to interference from endogenous substances of that material, notably catecholamines; and (3) they require preliminary clean-up of the sample before HPLC analysis can be performed. EXPERIMENTAL L-Tyrosine was obtained from Koch-Light (Colnbrook, Great Britain) and benzyloxyamine (o-benzylhydroxylamine hydrochloride), 6,7-climethyltetrahydropterin and 2-@I-morpholinoethane)sulfonic acid (MES) from Sigma (St. Louis, MO, U.S.A.). Other reagents (analytical-reagent grade) were supplied by E. Merck (Darmstadt, G.F.R.).
A novel and efficient synthesis of DOPA and DOPA peptides by oxidation of tyrosine residues with IBX
Tetrahedron Letters, 2009
An efficient route to 3,4-dihydroxylphenylalanine (DOPA) and DOPA peptides was described by oxidation of L-tyrosine and L-tyrosine derivatives with 2-iodoxybenzoic acid (IBX). DOPA was obtained after an situ reduction of the corresponding ortho-quinone with sodium dithionite. Oxidation reactions proceeded in good yields and high chemo-and regio-selectivity. The chirality of the DOPA residue was retained under the reaction conditions. The efficiency and the selectivity of the reaction were successfully tested using recyclable polymer-supported IBX.
Brain Research, 1996
The effect of 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) and l-tyrosine infusion on [11C]dopamine synthesis was analyzed in the striatum of Rhesus monkey using positron emission tomography (PET). The rate for decarboxylation from l-[β-11C]DOPA to [11C]dopamine was calculated using a graphical method with cerebellum as a reference region. Although the peripheral administration of 6R-BH4 at low dose (2 mg/kg) did not provide a significant increase in the rate of dopamine biosynthesis, a high dose of 6R-BH4 (20 mg/kg) induced an elevation of the rate. This 6R-BH4-induced elevation of the dopamine synthesis rate was further dose-dependently enhanced by the continuous infusion of l-tyrosine (0.2 and 1.0 μmol/min/kg). l-Tyrosine infusion with a rate of 1.0 μmol/min/kg caused an enhancement of the rate even during low dose administration of 6R-BH4 (2 mg/kg). l-Tyrosine infusion alone did not induce any elevation of the dopamine biosynthesis rate. The analysis of plasma indicated tha...