- Synthesis method of 3-(3, 4-dimethoxyphenyl)-L-alanine
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The invention relates to the technical field of chemical medicine intermediates, and provides a synthetic method of 3-(3, 4-dimethoxyphenyl)-L-alanine. The preparation method comprises the following steps: mixing water, veratraldehyde, ammonia water and hydantoin for condensation reaction to obtain condensation reaction liquid; ammonia water in the condensation reaction liquid is distilled out, residual feed liquid is directly subjected to a hydrogenation reduction reaction, and 3-(3, 4-dimethoxyphenyl)-L-alanine is obtained through alkaline hydrolysis and acidification. According to the method, the next step of reaction is directly carried out after ammonia water is evaporated from the condensation reaction liquid, the product of the condensation reaction does not need to be separated, the complicated post-treatment step after the condensation reaction is completed in the traditional method is avoided, the generation of three wastes is reduced, the environmental protection property is better, and meanwhile, the comprehensive yield of the target product is also improved. The result of the embodiment shows that when the 3-(3, 4-dimethoxyphenyl)-L-alanine is synthesized by adopting the method disclosed by the invention, the comprehensive yield of the product is 84 to 92 percent.
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Paragraph 0031-0032; 0033-0034; 0035-0036; 0037-0038
(2022/04/15)
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- Chemoenzymatic synthesis of L-3,4-dimethoxyphenyl-alanine and its analogues using aspartate aminotransferase as a key catalyst
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In this study, a chemoenzymatic synthesis method for the production of L-3,4-dimethoxyphenyl-alanine and its analogues from phenylpyruvate derivatives was developed. The aspartate aminotransferase from Escherichia coli was engineered by error prone PCR and the improved variants were identified. When 3, 4-dimethoxy phenylpyruvate was added by fed-batch on a preparative scale, L-3,4-dimethoxyphenyl-alanine was formed in 95.4% conversion and > 99% ee with the best aspartate aminotransferase variant as the catalyst. This study provided an efficient method for the production of methoxy substituted phenylalanines using the engineered aspartate aminotransferase.
- Yu, Jinhai,Li, Jing,Cao, Shuangyan,Wu, Ting,Zeng, Shuiyun,Zhang, Hongjuan,Liu, Junzhong,Jiao, Qingcai
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- Asymmetric synthesis of unnatural amino acids and tamsulosin chiral intermediate
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An efficient and enantioselective hydrogenation of N-acetylamino phenyl acrylic acids was successfully developed by using ruthenium catalyst. This methodology is important in the field of pharmaceuticals and provides a new process for the preparation of unnatural amino acids and tamsulosin chiral intermediate.
- Arava, Veera Reddy,Amasa, Srinivasulu Reddy,Goud Bhatthula, Bharat Kumar,Kompella, Laxmi Srinivas,Matta, Venkata Prasad,Subha
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supporting information
p. 2892 - 2897
(2013/09/02)
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- Pictet-Spengler cyclization vs. Aminal formation: Competing reaction pathways of benzo[b][1,7]naphthyridines controlled by the configuration
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Diastereoisomeric benzo[b][1,7]naphthyridines 13a,b were synthesized in nine steps from L-DOPA employing a Lewis acid-catalyzed cyclization of N-(4-methylpent-3-enyl)-a-amino aldehydes as the key step. Under aprotic Pictet-Spengler conditions, compounds 13a,b undergo different reaction pathways depending on the relative configuration. Whereas trans,cis-diastereoisomer 13a yielded the desired Pictet-Spengler cyclization product albeit in very low yield, the corresponding concave-shaped all-cis-diastereoisomer 13b undergoes intramolecular animal formation.
- Dickner, Tim,Laschat, Sabine
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p. 2064 - 2070
(2007/10/03)
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- New synthetic amino acids for the design and synthesis of peptide-based metal ion sensors
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The syntheses of two new nonstandard amino acids, Flu (6) and XBp (20), and a new synthesis of Dmd (12) are reported. These residues exhibit fluorescence, metal-coordination, and fluorescence-quenching properties, respectively. These building blocks have been incorporated into peptides via solid phase peptide synthesis to afford the prototype for a photoinduced electron transfer-based metal ion chemosensor. The fluorescence of the peptides is modulated upon metal binding. This results from a metal ion-induced conformational change that brings the side chains of the Flu and Dmd amino acids into proximity, thereby favoring photoinduced electron transfer (PET) fluorescence quenching.
- Torrado, Alicia,Imperiali, Barbara
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p. 8940 - 8948
(2007/10/03)
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- Stereospecific syntheses of the lignans: 2-S-(3,4-dimethoxybenzyl)-3-R-(3,4,5-trimethoxybenzyl) butyrolactone, and its positional isomeric lactone
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A short, versatile and stereospecific synthesis of two lignans 1 and 2, was achieved in 40% overall yield. Our strategy was based in the use of amino acids as chiral and readily available starting materials. Stereocontrolled transformation of amino acids to chiral organic phosphonates gave the key intermediate of the synthetic sequence. A Horner-Wadsworth-Emmons (HWE) reaction followed by selective reduction and stereospecific hydrogenation in the last step resulted in the title compounds with the desired absolute stereochemistry.
- Suarez,Lopez,Compagnone
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p. 1991 - 2001
(2007/10/02)
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- Efficient asymmetric synthesis of amino acids through hydrogenation of the didehydroamino acid residue in cyclic imino-ester derivatives
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The trisubstituted olefinic bond of chiral cyclic α,β-didehydroamino acid derivatives was hydrogenated in the presence of Pd/C with >95% diastereoface discrimination to give, after hydrolysis, the corresponding S-amino acids. The reduction of the double bond with L-selectride does not change the orientation of diastereoface discrimination and the diastereoselectivity is still high.
- Cativiela,Diaz-de-Villegas,Galvez
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p. 567 - 572
(2007/10/02)
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- Asymmetric synthesis X III: The stereocontrolled synthesis of (R)-α-amino acids via a double chiral induction
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The stereocontrolled synthesis of (R)-α-amino acids via a double chiral induction in alkylation of the ketimine derived from (+)-camphor and (+)-methyl glycinate which is a chiral match pair has been studied. (R)-α-amino acids with high optical purity 80-90% are obtained after hydrolysis of the alkylated products. We find that the chiral match which is the synergistic effect in a double chiral induction is very important to obtain the higher diastereoselectivity for the stereocontrolled synthesis.
- Yao Zhong,Guilan,Changyou,Huri,Lanjun,Aiqiao
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p. 1087 - 1090
(2007/10/02)
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- Mechanism of Stereospecific Production of L-Amino Acids from the Corresponding 5-Substituted Hydantoins by Bacillus brevis
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The mechanism of stereospecific production of L-amino acids from the corresponding 5-substituted hydantoins by Bacillus brevis AJ-12299 was studied.The enzymes involved in the reaction were partially purified by DEAE-Toyopearl 650M column chromatography and their properties were investigated.The conversion of DL-5-substituted hydantoins to the corresponding L-amino acids consisted of the following two successive reactions.The first step was the ring-opening hydrolysis to N-carbamoyl amino acids catalyzed by an ATP dependent L-5-substituted hydantoin hydrolase.This reaction was stereospecific and the N-carbamoyl amino acid produced was exclusively the L-form.N-Carbamoyl-L-amino acid was also produced from the D-form of 5-substituted hydantoin, which suggests that spontaneous racemization occurred in the reaction mixture.In the second step, N-carbamoyl-L-amino acid was hydrolyzed to L-amino acid by an N-carbamoyl-L-amino acid hydrolase, which was also an L-specific enzyme.The ATP dependency of the L-5-substituted hydantoin hydrolase was supposed to be the limiting factor in the production of L-amino acids from the corresponding 5-substituted hydantoins by this bacterium.
- Yamashiro, Akihiro,Kubota, Koji,Yokozeki, Kenzo
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p. 2857 - 2864
(2007/10/02)
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- GENERAL METHOD FOR THE ASYMMETRIC SYNTHESIS OF α-AMINO ACIDS VIA ALKYLATION OF THE CHIRAL NICKEL(II) SCHIFF BASE COMPLEXES OF GLYCINE AND ALANINE
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Nickel(II) complexes of Schiff bases derived from (S)-o-benzaldehyde and alanine (3), or (S)-O-benzophenone and alanine (4), or glycine (5) have been used for the asymmetric synthesis of α-amino acids under a variety of conditions.The method of choice consists of the reaction of the corresponding complex with the appropriate alkyl halide in DMF at 25 deg C using solid NaOH as a catalyst.Low diastereoselective excess (d.e.) is observed for the alkylation of complex (3) with benzyl bromide and allyl bromide.Large selectivity (80 percent) is observed for the alkylation of complex (4).Optically pure(R)- and (S)-O-benzyl-α-methyl-α-amino acids were obtained (70-90 percent) after the alkylated diastereoisomeric complexes had been seperated on SiO2 and hydrolysed with aqueous HCl.The initial chiral reagents were recovered (80-92 percent).The alkylation of complex (5) gave (S)-alanine, (S)-valine, (S)-phenylalanine, (S)-tryptophan, (S)-isoleucine, (S)-2-aminohexanoic acid, and 3,4-dimethoxyphenylalanine with optical yields of 70-92 percent.The optically pure α-amino acids were obtained after the separation of the alkylated diastereoisomeric complexes on SiO2.The stereochemical mechanism of the alkylation reaction is discussed.
- Belokon, Yuri N.,Bakhmutov, Vladimir I.,Chernoglazova, Nina I.,Kochetkov, Konstantin A.,Vitt, Sergei V.,et al.
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p. 305 - 312
(2007/10/02)
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- Mechanism of Asymmetric Production of L-Aromatic Amino Acids from the Corresponding Hydantoins by Flavobacterium sp.
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The mechanism of asymmetric production of L-aromatic amino acids from the corresponding hydantoins by Flavobacterium sp.AJ-3912 was examined by investigating the properties of the enzymes involved in the hydrolysis of 5-substituted hydantoins corresponding to aromatic amino acids (AAH).The enzymatic hydrolysis of AAH by Flavobacterium sp.AJ-3912 consisted of the following two successive reactions; a hydrolytic ring opening reaction of DL-AAH to L- and D-form N-carbamyl aromatic amino acids (NCA), involving an enzyme (hydantoin hydrolase) followed by a hydrolytic cleaving reaction of the L-form NCA to L-aromatic amino acids involving another enzyme (N-carbamyl-L-aromatic amino acid hydrolase, abbreviated as L-NCA hydrolase).The ring opening reaction involving hydantoin hydrolase was not stereospecific, but the NCA cleaving reaction involving L-NCA hydrolase was completely L-specific.The pathway for the conversion of the by-produced D-form NCA to L-aromatic amino acids was as follows; conversion of D-form NCA to D-AAH through the reverse reaction of hydantoin hydrolase, and then conversion of the D-AAH to L-AAH through spontaneous racemization, followed by the successive hydrolysis of the L-AAH to L-aromatic amino acids by hydantoin hydrolase and L-NCA hydrolase.
- Yokozeki, Kenzo,Hirose, Yoshiteru,Kubota, Koji
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p. 737 - 746
(2007/10/02)
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- Optimal Conditions for the Enzymatic Production of L-Aromatic Amino Acids from the Corresponding 5-Substituted Hydantoins
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The reaction conditions for the production of L-tryptophan from DL-5-indolylmethylhydantoin by Flavobacterium sp.AJ-3940, and the cultural conditions for the formation of the enzyme involved by this bacterium were investigated.The optimal pH of this reaction was around 8.5 and the optimal temperature was between 45 to 55 deg C.The amount of L-tryptophan produced was remarkably increased by the addition of inosine, which formed a water insoluble adduct with L-tryptophan, to the reaction mixture because of the release of end-product inhibition by L-tryptophan.This enzyme was inducibly and intracellulary produced by Flavobacterium sp.AJ-3940 in proportion to the increase in cell growth.Cells showing high activity were obtained using a medium containing 5 g glucose, 5 g (NH4)2SO4, 1 g KH2PO4, 3 g K2HPO4, 0.1 g MgSO4*7H2O, 0.01 g CaCl2*2H2O, 50 ml corn steep liquor and 3.5 g DL-5-indolylmethylhydantoin in a total volume of 1 liter (pH 7.0).Under the best conditions, 43 mg/ml of L-tryptophan was produced from 50 mg/ml of DL-5-indolylmethylhydantoin with a molar yield of 97percent in the presence of cells of flavobacterium sp.AJ-3940.In addition, other L-aromatic amino acids such as L-phenylalanine, L-tyrosine, L-DOPA and related L-amino acids were also produced from the corresponding 5-substituted hydantoins by this bacterium containing the L-tryptophan-producing enzyme induced by DL-5-indolylmethylhydantoin.
- Yokozeki, Kenzo,Sano, Konosuke,Eguchi, Chikahiko,Iwagami, Hisao,Mitsugi, Koji
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p. 729 - 736
(2007/10/02)
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