- Organocatalytic Decarboxylation of Amino Acids as a Route to Bio-based Amines and Amides
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Amino acids obtained by fermentation or recovered from protein waste hydrolysates represent an excellent renewable resource for the production of bio-based chemicals. In an attempt to recycle both carbon and nitrogen, we report here on a chemocatalytic, metal-free approach for decarboxylation of amino acids, thereby providing a direct access to primary amines. In the presence of a carbonyl compound the amino acid is temporarily trapped into a Schiff base, from which the elimination of CO2 may proceed more easily. After evaluating different types of aldehydes and ketones on their activity at low catalyst loadings (≤5 mol%), isophorone was identified as powerful organocatalyst under mild conditions. After optimisation many amino acids with a neutral side chain were converted in 28–99 % yield in 2-propanol at 150 °C. When the reaction is performed in DMF, the amine is susceptible to N-formylation. This consecutive reaction is catalysed by the acidity of the amino acid reactant itself. In this way, many amino acids were efficiently transformed to the corresponding formamides in a one-pot catalytic system.
- Claes, Laurens,Janssen, Michiel,De Vos, Dirk E.
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p. 4297 - 4306
(2019/08/26)
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- Efficient biosynthesis of β-alanine with a tandem reaction strategy to eliminate amide by-product in the nitrilase-catalyzed hydrolysis
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An efficient biosynthesis of β-alanine from 3-aminopropionitrile at high concentration has been developed using a one-pot bienzymatic cascade of a nitrilase and an amidase. The nitrilase BjNIT3397 from Bradyrhizobium japonicum strain USDA110 catalyzes the hydrolysis of 3-aminopropionitrile to β-alanine at the concentration up to 3.0 mol/L with the formation 23% of 3-aminopropanamide. In order to eliminate the by-product 3-aminopropanamide, we cloned and characterized a new amidase from Pseudomonas nitroreducens through gene mining. Under the optimal conditions (50 mmol/L Na2HPO4-NaH2PO4 buffer, pH 6.0, 40 °C), 2.0 mol/L (176 g/L) of 3-aminopropanamide was completely hydrolyzed within 12 h. A tandem reaction system was then established to eliminate the by-product 3-aminopropanamide and increase the production of β-alanine to 90% isolated yield with 15.02 g/(L.h) space-time-yield. These results demonstrated that the tandem reaction strategy was an effective method of eliminating the amide by-products in the nitrilase-catalyzed hydrolysis at high substrate concentration.
- Tao, Yanyang,Han, Chao,Wang, Min,Yao, Peiyuan,Yuan, Jing,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
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p. S60 - S67
(2018/04/17)
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- Nitrilase-catalyzed hydrolysis of 3-aminopropionitrile at high concentration with a tandem reaction strategy for shifting the reaction to β-alanine formation
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Given the importance of β-alanine, the nitrilase BjNIT3397 from Bradyrhizobium japonicum strain USDA110 was examined toward the hydrolysis of 3-aminopropionitrile. It has been found that nitrilase BjNIT3397 effectively hydrolyzed 3-aminopropionitrile with substrate concentration up to 3 M (210 g/L) at the pH 7.3 and temperature 30°C. With the increase of substrate concentration from 0.6 to 3 M, 3-aminopropanamide was formed and its percentage in the products was increased up to 33%. In order to reduce the formation of 3-aminopropanamide, aspartate ammonia-lyase and fumaric acid were added into the reaction system to consume the byproduct ammonia. As expected, the reaction was shifted toward the formation of β-alanine, resulting in the decrease of 3-aminopropanamide from 33% to 3%. Therefore, a tandem reaction strategy was developed to effectively prevent the formation of 3-aminopropanamide. This might also offer a possibility of producing β-alanine and L-aspartic acid in one process.
- Han, Chao,Yao, Peiyuan,Yuan, Jing,Duan, Yitao,Feng, Jinhui,Wang, Min,Wu, Qiaqing,Zhu, Dunming
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p. 113 - 118
(2015/03/18)
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- Thermodynamically controlled chemoselectivity in lipase-catalyzed aza-Michael additions
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Chemoselective synthesis of N-protected β-amino esters involving lipase-catalyzed aza-Michael additions and α,β-unsaturated precursors is mainly hampered by the two electrophilic sites present on these compounds. In order to control the chemoselectivity a solvent engineering strategy based on the thermodynamic behaviour of products in media of different polarity was designed. This strategy allowed to obtain aza-Michael adducts from benzylamine and different acrylates with high selectivity. In almost all reactions carried out in n-hexane, a non-polar solvent, aminolysis was avoided while the corresponding Michael adducts were exclusively synthesized in 53-78% yields. On the contrary, in reactions carried out in a polar solvent such as 2-methyl-2-butanol the aminolysis products were favoured. Thermodynamic analyses of these processes using the COSMO-RS method helped to understand some of the key factors affecting chemoselectivity and confirmed that a reliable estimation of the thermodynamic interactions of solutes and solvents allows an adequate selection of a reaction media that may lead to chemoselectivity.
- Rivera-Ramírez, José Domingo,Escalante, Jaime,López-Munguía, Agustín,Marty, Alain,Castillo, Edmundo
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supporting information
p. 76 - 82
(2015/01/30)
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- Synthesis of functionalized glutamine- and asparagine-type peptoids-scope and limitations
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N-Alkylated glycine oligomers ('peptoids') can serve as potent peptidomimetic systems. Installing different functional groups can often be a challenge, and minimizes yields and purities. Here, we describe the synthesis of different amide-containing submonomers which were obtained as free bases, as well as their incorporation into peptoids. By using the free amines, the coupling results on solid support could be improved, and various functionalized peptoids were prepared. Additionally, an interesting dimerization side reaction leading to cross-linked peptoids was observed during synthesis.
- Cardenal, Carmen,Vollrath, Sidonie B. L.,Schepers, Ute,Br?se, Stefan
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p. 2237 - 2248
(2013/02/23)
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- Quantitation of 3-aminopropionamide in potatoes - A minor but potent precursor in acrylamide formation
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3-Aminopropionamide (3-APA) has recently been suggested as a transient intermediate in acrylamide (AA) formation during thermal degradation of asparagine initiated by reducing carbohydrates or aldehydes, respectively. 3-APA may also be formed in foods by an enzymatic decarboxylation of asparagine. Using a newly developed method to quantify 3-APA based on liquid chromatography/ tandem mass spectrometry, it could be shown that the biogenic amine was present in several potato cultivars in different amounts. Further experiments indicated that 3-APA is formed during storage of intact potatoes (20 or 35 °C) or after crushing of the cells. The heating of 3-APA under aqueous or low water conditions at temperatures between 100 and 180 °C in model systems always generated more AA than in the same reaction of asparagine, thereby pointing to 3-APA as a very effective precursor of AA. While the highest yields measured were about 28 mol % in the presence of carbohydrates (170 °C; aqueous buffer), in the absence of carbohydrates, 3-APA was even converted by about 63 mol % into AA upon heating at 170 °C under aqueous conditions. Propanoic acid amides bearing an amino or hydroxy group in the α-position, such as 2-hydroxypropionamide and L-alaninamide, were ineffective in AA generation indicating that elimination occurs only from the β-position.
- Granvogl, Michael,Jezussek, Magnus,Koehler, Peter,Schieberle, Peter
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p. 4751 - 4757
(2007/10/03)
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- One-pot sequence for the decarboxylation of α-amino acids
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Treatment of an α-amino acid with N-bromosuccinimide in water at pH 5 or in an alcoholic-aqueous ammonium chloride mixture, followed by addition of nickel(II) chloride and sodium borohydride, effected an overall decarboxylation via an intermediate nitrile to afford the corresponding amine in good yield.
- Laval, Gilles,Golding, Bernard T.
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p. 542 - 546
(2007/10/03)
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- Compounds having growth hormone releasing activity
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Compounds that promote growth hormone releasing activity are disclosed. These compounds have the formula: A1-A2-X; A1-X′; or A1.-Y These compounds can be present in a pharmaceutical composition. The compounds can be used with a second compound that acts as an agonist at the growth hormone releasing hormone receptor or which inhibits the effects of somatostatin. These compounds can be used for a variety of uses such as treating hypothalamic pituitary dwarfism, osteoporosis, burns, or promoting wound healing.
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- Indolin-2-one derivatives, method for preparing them and pharmaceutical compositions containing them
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PCT No. PCT/FR97/02270 Sec. 371 Date Jun. 14, 1999 Sec. 102(e) Date Jun. 14, 1999 PCT Filed Dec. 11, 1997 PCT Pub. No. WO98/25901 PCT Pub. Date Jun. 18, 1998The invention relates to compounds with formula (I), a process for their preparation and pharmaceutical compositions containing them. These compounds have an excellent affinity for vasopressin and/or oxytocin
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- EPC-synthesis of β-amino acid derivatives through lithiated hydropyrimidines
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Racemic and enantiopure 2-tert-butyltetrahydropyrimidinones (from pivalaldehyde and 3-aminocarboxylic acids) are converted to Alloc-, Boc-, and Z-protected cyclic imino esters (7-10, Schemes 2-4). These are deprotonated to Li enaminates (K, L). Reactions with electrophiles (prim., sec. alkyl, allyl, benzyl, propargyl halides, aldehydes, imines, enoates) give good yields and are highly diastereoselective (products 11-42, Schemes 5-10). A two-step cleavage (removal of protecting group and hydrolysis) under very mild conditions converts the heterocyclic products to α-branched β-amino acid methyl esters (43-61, Schemes 11-13). The structure of the products is determined by NMR spectroscopy (Figure 1), by chemical correlation (Scheme 14), and by X-ray analysis (Figure 2, 3, 7, Table 1). A structure of the Li enaminates is proposed (Figure 4). Mechanistic models are derived for the reactions occurring with formation of two stereogenic centers with relative topicity like (Figures 5, 6).
- Seebach, Dieter,Boog, Alois,Schweizer, W. Bernd
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p. 335 - 360
(2007/10/03)
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- Bleomycin model complex bearing a carbamoyl derived substituent capable of coordination to the chelated metal ion as a sixth ligand
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A new, simple bleomycin (BLM) model compound bearing a carbamoyl group mimicking BLM's sugar-tagged carbamoyl moiety was synthesized and the physicochemical properties of its divalent metal complexes were studied. The Fe complex of the model compound exhi
- Arai, Takayuki,Shinozuka, Kazuo,Sawai, Hiroaki
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- S-[2-[(2'-Carbamoylethyl)amino]ethyl] phosphorothioate and related compounds as potential antiradiation agents
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A reinvestigation of the radiation protection activity of S-[2-[(2'-carbamylethyl)amino]ethyl] lithium hydrogen phosphorothioate (4a) revealed that this compound possessed good (70% protection at a dose of 600 mg/kg) activity. The thione and imino biososteres of 4, S-[2-(2'-thiocarbamylethylamino)ethyl] lithium hydrogen phosphorothioate (13a) and S-[2-(2'-amidinoethylamino)ethyl] phosphorothioate acid (18b) showed 100% protection at doses of 300 and 150 mg/kg, respectively. The N-methyl (4b) and tert-butyl (4c) analogues of amide 4a, the N-methyl (13b) analogue of the thioamide 13a, the N-methyl (18a) analogue of amidine (18b), and the cyclic amidine S-[2-[[2'-(4,5-dihydroimidozoyl)ethyl]amino]ethyl] lithium hydrogen phosphorothioate (21) all showed 80% protection at the highest dose tested.
- Carroll,Gopinathan,Philip
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p. 2501 - 2508
(2007/10/02)
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- THE REACTION OF BENZENE WITH N-(BENZYLOXYCARBONYL)-1-AMINOCYCLOPROPANE-1-CARBOXAMIDE
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The treatment of N-(benzyloxycarbonyl)-1-aminocyclopropane-1-carboxamide with benzene caused cleavage of the cyclopropane ring with the formation of a β-alaninamide derivative.
- Tamura, Masahiro,Jacyno, John,Stammer, Charles H.
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p. 5435 - 5436
(2007/10/02)
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