- The pharmacophore of a peptoid VEGF receptor 2 antagonist includes both side chain and main chain residues
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Here we identify the pharmacophore in a peptoid that antagonizes Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) in vitro and in vivo. Only three of the side chains in the peptoid are required for activity. Surprisingly, however, main chain atoms also form critical interactions with the receptor.
- Udugamasooriya, D. Gomika,Dunham, Geoff,Ritchie, Caroline,Brekken, Rolf A.,Kodadek, Thomas
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Read Online
- Activation of Water at the Active-Site Cavity of Zinc Phthalocyanine with Tris(pentafluorophenyl)borane
-
Activation of water bound with Zn2+ has attracted much attention as an artificial model of natural enzymes. Despite many attempts, water activation accompanied with a change in the coordination geometry of Zn2+ in complexes remains a challenge. In this study, we discover a new structure that is composed of partially protonated zinc phthalocyanine (ZnPc), hydroxide ion, and tris(pentafluorophenyl)borane (TPFB). The coordination of TPFB with water bounded with ZnPc results in the dissociation of water, and the dissociated proton from water moves to one nitrogen atom of the phthalocyanine ring through the intramolecular proton transfer. On the basis of this reaction, the coordination geometry transforms from a five-coordinated to a distorted tetrahedral species. The Zn2+-bound hydroxide nucleophile in the ZnPc-TPFB complex attacks amide of ε-caprolactam to produce hydrolyzed 6-aminohexanoic acid in toluene.
- Ikeuchi, Takuro,Kudo, Ryota,Yoshii, Tatsuya,Kobayashi, Nagao,Kitazawa, Yu,Kimura, Mutsumi
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Read Online
- Gram-scale synthesis of carboxylic acids via catalytic acceptorless dehydrogenative coupling of alcohols and hydroxides at an ultralow Ru loading
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Acceptorless dehydrogenative coupling (ADC) of alcohols and water/hydroxides is an emergent and graceful approach to produce carboxylic acids. Therefore, it is of high demand to develop active and practical catalysts/catalytic systems for this attractive transformation. Herein, we designed and fabricated a series of cyclometallated N-heterocyclic carbene-Ru (NHC-Ru) complexes via ligand tuning of [Ru-1], the superior complex in our previous work. Gratifyingly, gram-scale synthesis of carboxylic acids was efficiently enabled at an ultralow Ru loading (62.5 ppm) in open air. Moreover, effects of distinct ancillary NHC ligands and other parameters on this catalytic process were thoroughly studied, while further systematic studies were carried out to provide rationales for the activity trend of [Ru-1]-[Ru-7]. Finally, determination of quantitative green metrics illustrated that the present work exhibited superiority over representative literature reports. Hopefully, this study could provide valuable input for researchers who are engaging in metal-catalyzed ADC reactions.
- Chen, Cheng,Cheng, Hua,Verpoort, Francis,Wang, Zhi-Qin,Wu, Zhe,Yuan, Ye,Zheng, Zhong-Hui
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- An Integrated Cofactor/Co-Product Recycling Cascade for the Biosynthesis of Nylon Monomers from Cycloalkylamines
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We report a highly atom-efficient integrated cofactor/co-product recycling cascade employing cycloalkylamines as multifaceted starting materials for the synthesis of nylon building blocks. Reactions using E. coli whole cells as well as purified enzymes produced excellent conversions ranging from >80 and 95 % into desired ω-amino acids, respectively with varying substrate concentrations. The applicability of this tandem biocatalytic cascade was demonstrated to produce the corresponding lactams by employing engineered biocatalysts. For instance, ?-caprolactam, a valuable polymer building block was synthesized with 75 % conversion from 10 mM cyclohexylamine by employing whole-cell biocatalysts. This cascade could be an alternative for bio-based production of ω-amino acids and corresponding lactam compounds.
- Sarak, Sharad,Sung, Sihyong,Jeon, Hyunwoo,Patil, Mahesh D.,Khobragade, Taresh P.,Pagar, Amol D.,Dawson, Philip E.,Yun, Hyungdon
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p. 3481 - 3486
(2020/12/17)
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- Preparation method of 6-aminocaproic acid
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The invention discloses a preparation method of 6-aminocaproic acid, which comprises the following steps: by using caprolactam as a raw material, carrying out alkaline hydrolysis, neutralization treatment, desalination treatment and refining treatment to obtain the 6-aminocaproic acid, wherein the alkaline hydrolysis is carried out on caprolactam, sodium hydroxide and water at a certain temperature and under a certain pressure, a certain temperature is 115-125 DEG C, a certain pressure is 0.15-0.3 MPa, and the reaction time of alkaline hydrolysis does not exceed 1.5 hours. According to the alkaline hydrolysis method disclosed by the invention, the hydrolysis time is shortened through pressurization, so that the generation of by-products can be effectively inhibited under the condition of ensuring complete hydrolysis, and therefore, the alkaline hydrolysis method not only has relatively high reaction yield, but also has relatively high product purity.
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Paragraph 0027-0036
(2021/03/18)
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- Method for preparing aminocaproic acid
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The invention discloses a method for preparing aminocaproic acid. The method comprises the following steps: in the presence of heteropolyacid or concentrated sulfuric acid, carrying out hydrolysis reaction on caprolactam and water at 70-80 DEG C for 6-15 hours, sequentially carrying out adsorption by virtue of a cationic resin exchange column and an anionic resin exchange column, and carrying outrefining, so as to obtain the product. According to the method for preparing aminocaproic acid provided by the invention, the maximum feeding scale is 300kg of caprolactam, and the yield of the finally obtained aminocaproic acid is about 99% relative to caprolactam.
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Paragraph 0026-0068
(2020/05/14)
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- IMPROVED PROCESS FOR THE PREPARATION OF 6-AMINOHEXANOIC ACID
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The present invention relates to highly pure 6-aminohexanoic acid of formula-1 which is free of organic volatile impurities, caprolactam impurity and improved process for its preparation thereof. The present invention also relates to an improved process for the preparation of caprolactam of formula-2 which is used for the preparation of 6-aminohexanoic acid of formula-1.
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Paragraph 10-11
(2020/03/02)
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- Generation of amine dehydrogenases with increased catalytic performance and substrate scope from ε-deaminating L-Lysine dehydrogenase
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Amine dehydrogenases (AmDHs) catalyse the conversion of ketones into enantiomerically pure amines at the sole expense of ammonia and hydride source. Guided by structural information from computational models, we create AmDHs that can convert pharmaceutically relevant aromatic ketones with conversions up to quantitative and perfect chemical and optical purities. These AmDHs are created from an unconventional enzyme scaffold that apparently does not operate any asymmetric transformation in its natural reaction. Additionally, the best variant (LE-AmDH-v1) displays a unique substrate-dependent switch of enantioselectivity, affording S- or R-configured amine products with up to >99.9% enantiomeric excess. These findings are explained by in silico studies. LE-AmDH-v1 is highly thermostable (Tm of 69 °C), retains almost entirely its catalytic activity upon incubation up to 50 °C for several days, and operates preferentially at 50 °C and pH 9.0. This study also demonstrates that product inhibition can be a critical factor in AmDH-catalysed reductive amination.
- Tseliou, Vasilis,Knaus, Tanja,Masman, Marcelo F.,Corrado, Maria L.,Mutti, Francesco G.
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- Highly active bidentate N-heterocyclic carbene/ruthenium complexes performing dehydrogenative coupling of alcohols and hydroxides in open air
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Eight bidentate NHC/Ru complexes, namely [Ru]-1-[Ru]-8, were designed and prepared. In particular, [Ru]-2 displayed extraordinary performance even in open air for the dehydrogenative coupling of alcohols and hydroxides. Notably, an unprecedentedly low catalyst loading of 250 ppm and the highest TON of 32 800 and TOF of 3200 until now were obtained.
- Wang, Zhi-Qin,Tang, Xiao-Sheng,Yang, Zhao-Qi,Yu, Bao-Yi,Wang, Hua-Jing,Sang, Wei,Yuan, Ye,Chen, Cheng,Verpoort, Francis
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supporting information
p. 8591 - 8594
(2019/07/25)
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- Method for preparing 6-aminocaproic acid
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The invention discloses a method for preparing 6-aminocaproic acid. The method includes the steps: (1) dissolving caprolactam in acidic water solution with the concentration of 5-15%, stirring mixturefor 2-10 hours at the temperature of 80-120 DEG C, and distilling the mixture in a pressure reduction manner to obtain white solid; (2) adding a polar solvent until the solid is completely dissolved,slowly leading in ammonia gas until reaction is completed, or dripping organic amine, continuing to stir mixture for 1-12 hours at the temperature of 0-80 DEG C after dripping is completed, and filtering the mixture to obtain an aminocaproic acid crude product; (3) washing the crude product to obtain the 6-aminocaproic acid the purity higher than 99.0%. The molar ratio of the led in ammonia gas or amidogen in the organic amine to the caprolactam is (1-4.5):1. The method has the advantages of low cost, environmental friendliness, high product quality, simplicity and easiness in operation, mildreaction condition and the like, reaction materials can be easily recovered, and a process is more suitable for mass production.
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Paragraph 0027-0062
(2019/03/08)
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- Parallel anti-sense two-step cascade for alcohol amination leading to ω-amino fatty acids and α,ω-diamines
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Running two two-step cascades in parallel anti-sense to transform an alcohol to an amine allowed the conversion of ω-hydroxy fatty acids (ω-HFAs) and α,ω-diols to the corresponding ω-amino fatty acids (ω-AmFAs) and α,ω-diamines, respectively. The network required only two enzymes namely an aldehyde reductase (AHR) and a transaminase (TA). Benzylamine served on the one hand as amine donor and on the other hand after deamination to benzaldehyde also as oxidant. All ω-HFAs tested were efficiently transformed to their corresponding ω-AmFAs using purified enzymes as well as a whole-cell system, separately expressing both the enzymes, with conversions ranging from 80-95%. Additionally, a single-cell co-expressing all enzymes successfully produced the ω-AmFAs as well as the α,ω-diamines with >90% yield. This system was extended by employing a lactonase, enabling the transformation of ?-caprolactone to its corresponding ω-AmFA with >80% conversion.
- Sung, Sihyong,Jeon, Hyunwoo,Sarak, Sharad,Ahsan, Md Murshidul,Patil, Mahesh D.,Kroutil, Wolfgang,Kim, Byung-Gee,Yun, Hyungdon
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supporting information
p. 4591 - 4595
(2018/10/23)
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- ISOLATION AND PURIFICATION OF 6-AMINOCAPROIC ACID
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The present invention relates to a new process for the isolation and purification of 6-aminocaproic acid, which is a known inhibitor of enzymes responsible for fibrinolysis and is used in the treatment of coagulopathies and severe post-operative bleedings.
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Paragraph 0052; 0058
(2017/06/13)
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- Method for preparing 6-bromotriphenylphosphonio-n-caproic acid
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The invention relates to the field of production and preparation of compounds and particularly relates to a method for preparing 6-bromotriphenylphosphonio-n-caproic acid. The method comprises the following steps: (1) subjecting caprolactam to a hydrolysis reaction, so as to prepare 6-aminocaproic acid; (2) subjecting 6-aminocaproic acid to a diazotization reaction, so as to prepare 6-hydroxycaproic acid; (3) subjecting 6-hydroxycaproic acid to a bromization reaction, so as to prepare 6-bromocaproic acid; and (4) enabling 6-bromocaproic acid to react with triphenyl phosphine, thereby obtaining 6-bromotriphenylphosphonio-n-caproic acid.
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Paragraph 0048-0055; 0056-0063; 0064-0071; 0072-0079
(2017/08/29)
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- METHODS OF PRODUCING 6-CARBON MONOMERS FROM 8-CARBON COMPOUNDS
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This document describes biochemical pathways for producing 6-hydroxyhexanoic acid using a monooxygenase to form a 7-hydroxyoctanoate intermediate, which can be converted to 6-hydroxyhexanoate using a polypeptide having monooxygenase, secondary alcohol dehydrogenase, or esterase activity. 6-hydroxyhexanoic acid can be enzymatically converted to adipic acid, caprolactam, 6-aminohexanoic acid, hexamethylenediamine or 1,6-hexanediol. This document also describes recombinant hosts producing 6-hydroxyhexanoic acid as well as adipic acid, caprolactam, 6-aminohexanoic acid, hexamethylenediamine and 1,6-hexanediol.
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Page/Page column 49
(2016/06/14)
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- Caprolactam and manufacturing method thereof
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PROBLEM TO BE SOLVED: To provide ε-caprolactam in which the content of 7-methyl-ε-caprolactam is 0.025 mass% or less, preferably 0.020 mass% or less and further the content of 3-methyl-ε-caprolactam is 0.004 mass% or less, preferably 0.003 mass%, and to provide a method for producing the same.SOLUTION: There are provided ε-caprolactam synthesized via 6-amino-2-chlorocaproic acid and 6-aminocaproic acid using lysine and/or a salt of lysine as a raw material and a method for producing the same.
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Paragraph 0057
(2017/06/21)
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- General Synthesis of Amino Acid Salts from Amino Alcohols and Basic Water Liberating H2
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An atom-economical and environmentally friendly method to transform amino alcohols to amino acid salts using just basic water, without the need of pre-protection or added oxidant, catalyzed by a ruthenium pincer complex, is developed. Water is the solvent, the source of the oxygen atom of the carboxylic acid group, and the actual oxidant, with liberation of dihydrogen. Many important and useful natural and unnatural amino acid salts can be produced in excellent yields by applying this new method.
- Hu, Peng,Ben-David, Yehoshoa,Milstein, David
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supporting information
p. 6143 - 6146
(2016/06/09)
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- A green and sustainable phosphine-free NHC-ruthenium catalyst for selective oxidation of alcohols to carboxylic acids in water
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In this work, we present a new catalytic system for the selective dehydrogenative oxidation of primary alcohols to carboxylic acids using a phosphine-free NHC-ruthenium catalyst in water under mild reaction conditions. With this catalytic system, a variety of primary alcohols have been converted to carboxylic acids respectively, in aqueous media, without using any additional oxidant; the only side product in this reaction is molecular hydrogen. This novel synthetic protocol is applied for direct oxidation of biologically active monosaccharides and polymers with primary alcohol groups in the side chain. The use of water as a solvent and oxygen donor as well as the absence of any toxic oxidizing agent make this atom economical reaction interesting from an environmental point of view.
- Malineni, Jagadeesh,Keul, Helmut,M?ller, Martin
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supporting information
p. 17409 - 17414
(2015/10/12)
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- METHODS OF PRODUCING COMPOUNDS FROM 5-(HALOMETHYL)FURFURAL
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Provided herein are methods of producing compounds, such as cyclohexanone, hexanediamine, hexanediol, hexamethylenediamine, caprolactam and nylon, from 5- (halomethyl)furfural.
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- Introducing an in situ capping strategy in systems biocatalysis to access 6-aminohexanoic acid
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The combination of two cofactor self-sufficient biocatalytic cascade modules allowed the successful transformation of cyclohexanol into the nylon-6 monomer 6-aminohexanoic acid at the expense of only oxygen and ammonia. A hitherto unprecedented carboxylic acid capping strategy was introduced to minimize the formation of the deadend intermediate 6-hydroxyhexanoic acid. For this purpose, the precursor ε-caprolactone was converted in aqueous medium in the presence of methanol into the corresponding methyl ester instead of the acid. Hence, it was shown for the first time that esterases-specifically horse liver esterase-can perform the selective ring-opening of ε-caprolactone with a clear preference for methanol over water as the nucleophile.
- Sattler, Johann H.,Fuchs, Michael,Mutti, Francesco G.,Grischek, Barbara,Engel, Philip,Pfeffer, Jan,Woodley, John M.,Kroutil, Wolfgang
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supporting information
p. 14153 - 14157
(2015/02/19)
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- Method of Making 6-Aminocaproic Acid As Active Pharmaceutical Ingredient
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The present invention provides a method for making 6-aminocaproic acid as an active pharmaceutical ingredient. The method comprises: performing a hydrolysis procedure to have ε-caprolactam react with acid or base to generate a first reaction mixture, performing a modification procedure to have a solubility regulating agent reacts with 6-aminocaproic acid in the first reaction mixture to form a second reaction mixture including an aminocaproic acid intermediate, performing a separation procedure to have the intermediate separated from the second reaction mixture and performing a hydrogenation procedure to have the aminocaproic acid intermediate hydrogenated to form a 6-aminocaproic acid product.
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Paragraph 0056; 0056
(2014/02/16)
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- Production of L-tryptophan by enantioselective hydrolysis of d,l-tryptophanamide using a newly isolated bacterium
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Bacterial strain ZJB-09211 capable of amidase production has recently been isolated from soil samples. The strain is able to asymmetrically hydrolyze l-tryptophanamide from d,l-tryptophanamide to produce l-tryptophan in high yield and with excellent stereoselectivity (enantiomeric excess > 99.9 %, and enantiomeric ratio > 200). Strain ZJB-09211 has been identified as Flavobacterium aquatile based on the cell morphology analysis, physiological tests, and the 16S rDNA sequence analysis. Optimization of the fermentation medium led to an about six-fold increase in the amidase activity of strain ZJB-09211, which reached 501.5 U L-1. Substrate specifity and stereoselectivity investigations revealed that amidase of F. aquatile possessed a broad substrate spectrum and high enantioselectivity.
- Xu, Jian-Miao,Chen, Ben,Wang, Yuan-Shan,Zheng, Yu-Guo
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p. 1262 - 1270
(2013/07/19)
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- PRODUCTION OF CAPROLACTAM FROM CARBOHYDRATE-CONTAINING MATERIALS
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The present invention generally relates to processes for the conversion of glucose to caprolactam employing chemocatalytic oxidation and reduction reactions. The present invention also includes processes for the conversion of glucose to caprolactam via amido polyhydroxy acid products and amidocaproic acid or derivatives thereof. The present invention also includes processes that catalytically oxidize an amidopolyol to amidopolyhydroxy acid or derivatives thereof, and processes that catalytically hydrodeoxygenate amino or amido polyhydroxy acid or derivatives thereof to an amino or amidocaproic acid product. The amino or amidocaproic acid product may then be converted to caprolactam. The present invention also includes products produced by such processes and products producable from such products.
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Page/Page column 12
(2012/10/23)
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- Biological synthesis of difunctional alkanes from carbohydrate feedstocks
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Aspects of the invention relate to methods for the production of difunctional alkanes in host cells. In particular, aspects of the invention describe components of genes associated with the difunctional alkane production from carbohydrate feedstocks in host cells. More specifically, aspects of the invention describe metabolic pathways for the production of adipic acid, aminocaproic acid, caprolactam, and hexamethylenediamine via 2-ketopimelic acid.
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- METHOD FOR PREPARING ε-CAPROLACTAM FROM N-ACYL-6-AMINOCAPROIC ACID
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The invention relates to a method for preparing ε-caprolactam comprising deacylating N-acyl-6-aminocaproic acid and forming ε-caprolactam. The deacylation may be carried out chemically or biocatalytically. The invention further relates to a host cell, 5 comprising a recombinant vector comprising a nucleic acid sequence encoding an enzyme capable of catalysing the formation of 6-aminocaproic acid from N-acyl-6- aminocaproic acid.
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Page/Page column 10-11
(2010/04/28)
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- PREPARATION OF 6-AMINOCAPROIC ACID FROM α-KETOPIMELIC ACID
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The invention relates to a method for preparing 6-aminocaproic acid (hereinafter also referred to as '6-ACA')usinga biocatalyst. The invention further relates to a method for preparing e-caprolactam (hereafter referred to as 'caprolactam') by cyclising such 6-ACA. The invention further relates to a host cell, a micro-organism, or a polynucleotidewhich may be used inthe preparation of 6-ACA or caprolactam.
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Page/Page column 38-39
(2009/10/22)
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- Design and synthesis of novel sulfonamide-containing bradykinin hB 2 receptor antagonists. 2. Synthesis and structure-activity relationships of α,α-cycloalkylglycine sulfonamides
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Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.
- Fattori, Daniela,Rossi, Cristina,Fincham, Christopher I.,Caciagli, Valerio,Catrambone, Fernando,D'Andrea, Piero,Felicetti, Patrizia,Gensini, Martina,Marastoni, Elena,Nannicini, Rossano,Paris, Marielle,Terracciano, Rosa,Bressan, Alessandro,Giuliani, Sandro,Maggi, Carlo A.,Meini, Stefania,Valenti, Claudio,Quartara, Laura
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p. 550 - 565
(2007/10/03)
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- Process for the preparation of amino acid esters and their acid addition salts
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Preparation of amino acids, peptide esters and/or their acid addition salts of monomers or polymers amino acids, peptides, proteins or alcohols (I), where the reaction is carried out in supercritical alcohols.
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Page/Page column 5; 6
(2008/06/13)
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- Process for preparing amino acid esters and their acid addition salts
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The invention provides a process for preparing amino acid esters and/or their acid addition salts from monomeric or polymeric amino acids, peptides, proteins and alcohols, which comprises carrying out the reaction in supercritical alcohols, preferably at pressures and temperatures which are at least 5% above the critical parameters, the alcohols serving both as the solvent and as reactants.
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Page/Page column 3-4
(2008/06/13)
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- Process for production of high-temperature and high-pressure fluid and high-temperature and high-pressure reaction system
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The present invention provides a method for the production of a high-temperature high-pressure fluid which can be caused to reach specified conditions in a short time, a high-temperature high-pressure reaction method, and a reaction system for the same, and the present invention comprises a method for the production of a high-temperature high-pressure fluid in which the reactants can be caused to reach a prescribed temperature in 5 seconds or less by mixing two or more high-pressure fluids at different temperatures in a flow system, a high-temperature high-pressure reaction method which utilizes this production method of a high-temperature high-pressure fluid, and which reduces the temperature elevation time to the prescribed reaction temperature to 5 seconds or less by mixing a carrier fluid at a temperature higher than the prescribed reaction temperature with substrate solution(s) at a temperature of 100° C. or lower and reacting these fluids inside a reaction vessel, thus suppressing side reactions that occur during the temperature elevation and making it possible to perform short-time chemical reactions efficiently and selectively, and a reaction system for this reaction method.
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- Process for producing lactam
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It is an object of the present invention to provide an efficient method of continuously producing a lactam in high-temperature high-pressure water, and the present invention relates to a method of producing a lactam characterized by efficiently synthesizing the lactam while suppressing oxime hydrolysis by introducing an oxime as a reaction substrate and an acid into a reaction zone through which high-temperature high-pressure water is flowing, or introducing an oxime into flowing high-temperature high-pressure water containing an acid, thus raising the temperature of the reaction substrate to put the reaction substrate into a prescribed high-temperature high-pressure state within a short time and subjecting the reaction substrate to reaction; through the method, the lactam can be efficiently and continuously synthesized at a high rate from the oxime using an acid catalyst in water at a high temperature of at least 250° C. and a high pressure of at least 15 MPa.
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- PROCESS FOR PRODUCING LACTAM
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A process for continuously producing a lactam in water at a high temperature under a high pressure. Namely, a process for producing a lactam characterized by selectively synthesizing the lactam without causing hydrolysis by introducing an oxime into flowing water at a high temperature under a high pressure, wherein the lactam is continuously synthesized at a high rate from the oxime in water at a high temperature of 250 °C or more under a high pressure of 12 Mpa or more.
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- Production of 6-aminocaproic acid
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A process for making 6-aminocaproic acid by hydroformylating 3-pentenenitrile to produce 3-, 4-, and 5-formylvaleronitrile (FVN mixture), oxidizing the FVN mixture to produce 3-, 4-, and 5-cyanovaleric acid; hydrogenating the resulting product to produce 6-aminocaproic acid, 5-amino-4-methylvaleric acid, and 4-amino-3-ethylbutyric acid; and isolating 6-aminocaproic acid from the reaction product. The resulting 6-aminocaproic acid can be cyclized to produce caprolactam.
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Page column 7-8
(2008/06/13)
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- Process for the preparation of ε-caprolactam
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Process for the preparation of ε-caprolactam, in which in a step (a) a compound with the general formula: O=CH—(CH2)4—C(O)—R??(1) in which R is —OH, —NH2or O—R′, in which R′ is an organic group with 1 to 10 carbon atoms, is contacted with ammonia and hydrogen in a suitable solvent at elevated pressure in the presence of a hydrogenation catalyst to a mixture of primary amino compounds and ε-caprolactam, followed by a separate second step (b) in which the primary amino compounds are reacted to ε-caprolactam, wherein the solvent in step (a) is an aqueous medium, including water, the yield to ε-caprolactam in step (a) is more than 10%, calculated on the initial molar amount of the compound according to formula (1), that ε-caprolactam is separated from the aqueous mixture obtained in step (a) by extraction and that the aqueous mixture resulting from the extraction, containing the primary amino compounds, is used in step (b).
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Page column 11,12
(2008/06/13)
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- Absolute rate constants for the formation of nitrogen-centred radicals from chloramines/amides and their reactions with antioxidants
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Pulse radiolysis techniques have been employed to investigate the one-electron reduction of a variety of chloramines and chloramides. These include models for the side-chain of Lys (6-aminohexanoic acid chloramine and α-N-acetyl-Lys chloramine), Gly chloramine, β-alanine chloramine and two models of protein backbone amides, the chloramides of cyclo-(Gly)2 and cyclo-(Ala)2. The molar absorption coefficients and stabilities of these chloramines/amides have been determined. The one-electron reduction of these chloramine/amide species by hydrated electrons occurs with second-order rate constants of the order of 109-1010 M-1 s-1, and results in cleavage of the N-Cl bonds to yield nitrogen-centred radicals and chloride ions (as measured by high performance ion chromatography). The reactivities of the nitrogen-centred radicals have been investigated with the readily oxidisable quenchers, hydroquinone and Trolox. These quenchers were used as models of the in vivo antioxidants, ubiquinol-10 and α-tocopherol, and react with second-order rate constants between 2 × 107 and 1 × 108 M-1 s-1. No evidence was obtained in these pulse radiolysis experiments for a rapid rearrangement of the oxidising nitrogen-centred radicals to reducing carbon-centred radicals, though such reactions have been indicated in previous EPR studies.
- Pattison, David I.,Davies, Michael J.,Asmus, Klaus-Dieter
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p. 1461 - 1467
(2007/10/03)
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- Targeted oligonucleotide conjugates
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The present invention provides improved ingress of therapeutic and other moieties into cellular targets. In accordance with preferred embodiments, complexes are provided which carry primary moieties, chiefly therapeutic moieties, to such target cells. Such complexes preferably feature cell surface receptor ligands to provide specificity. Such ligands are preferably bound to primary moieties through polyfunctional manifold compounds.
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- Process for preparing caprolactam
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A simple and single step process for producing caprolactam comprising reacting 5-formylvaleric acid or an ester thereof in a solvent of water and/or an alcohol with hydrogen and ammonia in the presence of a noble metal catalyst supported by a carrier at 80° to 300° C. under a pressure of 10 to 120 atm, whereby amination, acidification, dehydration and cyclization occur to obtain caprolactam.
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- Synthesis of ω-nitro acids and ω-amino acids by ring cleavage of α- nitrocycloalkanones
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The reaction of various α-nitrocycloalkanones 1 with aqueous 0.05 M NaOH, at 80 °C, in the presence of cetyltrimethylammonium chloride (CTACl) as a cationic surfactant, produces ω-nitro acids 2 in good yields. Reduction of the latter with HCOONH4/Pd-C, in methanol, at 80 °C affords ω-amino acids 3. The synthesis of methyl 9-oxodecanoate (8) is also reported.
- Ballini, Roberto,Papa, Fabrizio,Abate, Corrado
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- Lactams in sulfuric acid. The mechanism of amide hydrolysis in weak to moderately strong aqueous mineral acid media
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Reaction rate constants obtained in moderately concentrated sulfuric acid for the hydrolysis of simple lactams of ring sizes five, six, seven, and eight as a function of acidity and temperature have been analyzed using the excess acidity kinetic method. The basicity constants for these substrates have been recalculated; the 13C NMR spectra used to obtain these values are very sensitive to medium effects. It was found that the basicities of the lactams at 0.003-0.1 M lactam concentration were over half a pK unit more basic than they were at 0.5 M lactam, presumably because of the medium effect. Apart from this, the rate constant results obtained at different times by different groups using different techniques for monitoring the kinetics are in adequate agreement. The excess acidity analysis showed that the kinetics could be fitted according to the 'three-water-molecule followed by one-water-molecule' mechanistic scenario previously found, or could just as well be fitted by a 'one-water-molecule followed by unknown mechanism' scenario, with the mechanistic change taking place at 50 wt.% sulfuric acid for all the substrates. Other evidence makes the latter seem the more likely possibility of the two, and activation parameters based upon the 'one-water- molecule' process were determined. Sufficient data points to enable the unknown mechanism to be established were not present; possible mechanisms applicable in media more concentrated than 50 wt.% sulfuric acid are discussed. Previously obtained values of the parameter r, the number of water molecules involved with the substrate in A2 processes, are now questionable.
- Cox, Robin A.
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p. 649 - 656
(2007/10/03)
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- Peptides with an insulin-like action
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Peptides with an insulin-like action, of formula I: STR1 in which G is a hydrogen atom, an amino add residue, or a monosubstituted or polysubstituted amino acid; D is an amino acid residue, a phosphoamino acid residue, a monosaccharide residue, or a covalent bond; E is --NH--(CH2)n --NR52, a glycerol residue, or --NH--(CH2)p --R6 --R7 ; R1 is (C1 -C4)-alkyl or =O; R2 is a sulfhydryl protecting group, (C1 -C3)-alkyl, or a hydrogen atom; R3 and R4, independently of one another, are a hydrogen atom or methyl; R5, each being identical or different, is a hydrogen atom, 1 to 6 monosaccharide residues, or 1 to 6 monosubstituted or polysubstituted monosaccharide residues; R6 is O PO4 H, PO2 H, NHCOO, S or OCOO; R7 is a hydrogen atom, 1 to 6 monosaccharide residues, or 1 to 6 monosubstituted or polysubstituted monosaccharide residues; w is an integer 1 or 2; their preparation and use for treatment of diabetes mellitus or insulin-independent diabetes.
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- Sulphocoumarin-containing nucleotides and their use in processes for detecting nucleic acids
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The invention relates to the preparation, as substituents, of nucleotides possessing a fluorescent coumarin residue, the enzymic incorporation of these nucleotides into nucleic acids and the detection of nucleic acids of defined sequence by hybridization with a complementary, coumarin-labelled nucleic acid.
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- Disazo dyestuffs
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Disazo dyestuffs have been found which, in the form of the free acid, correspond to the formula (I) STR1 represents H or an optionally substituted aliphatic or aromatic radical and R1 to R6 and A have the meaning given in the description, which are outstandingly suitable for inkjet printing.
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- Synthesis and Physicochemical Properties of Schiff Bases of Amino Acids with Salicylaldehyde
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A series of the Schiff bases of α- and ω-amino acids with salicylaldehyde was synthesized.The physicochemical properties of the substances obtained, including the fluorescent characteristics, were examined, and the hydrolysis constants at pH 6.0, 7.0, and 8.0 were determined.Key words: amino acids, hydroxybenzaldehyde, Schiff bases, fluorescence, hydrolysis constant
- Lurie, E. Yu.,Mosina, E. M.,Efremova, A. A.,Kaplun, A. P.,Shvets, V. I.
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p. 520 - 523
(2007/10/03)
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- Bifunctional isothiocyanate derived thiocarbonyls as ligands for metal binding
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This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, isothiocyanate derived thiocarbonyls for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.
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- Labeling reagents useful for the chemical attachment of nitrophenyl derivative ligands to DNA probes
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This invention discloses methods and compounds for covalently linking nitro-, dinitro- and trinitrophenyl to DNA and the resulting nitro-, dinitro-, and trinitrophenyl labeled DNA reagents. Reagents for the in situ detection of a chromosome or a region of a chromosome are disclosed. These reagents include a multiplicity of DNA sequences that are complementary to different portions of the chromosome or chromosome region to be detected. Multiple nitro-, dinitro- or trinitrophenyl labels are covalently linked to the DNA sequences by means of an amino acid linking group. These labeled reagents are contacted under hybridizing conditions with the chromosome or chromosome region of interest. Any binding of the reagent with the chromosome or chromosome region of interest may then be detected by immunological techniques.
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- Prodrug derivatives of carboxylic acid drugs
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Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
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- Process for the dyeing of leather with anionic dyes and polyaminoamide resin as dyeing auxiliary
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To improve the affinity of anionic dyestuffs in the dyeing of leather materials, polycondensation products consisting of at least one amine of the formula STR1 in which the radicals have the meanings mentioned in the description with one dicarboxylic acid and, if desired, ω-aminocarboxylic acid or its lactam are highly suitable.
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- Band-shape Analysis and Resolution of Electronic Spectra of Pyridoxal 5'-Phosphate with Amino Acids
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Formation equilibria of Schiff bases of pyridoxal 5'-phosphate (PLP) and different amino acids have been studied over a wide range of pH.The acid dissociation constant and absorption spectrum of every ionic species have been calculated.The latter has been resolved into components with log-normal curves, to provide a precise description of the band shapes, the peak positions and the area under the curves, which allowed the estimation of tautomerization constants and microscopic acid dissociation constants.Because of the acidity of the α-hydrogen of the amino acids, α-amino acid Schiff bases are in equilibrium with quinonoid forms which are hydrolysed to yield pyridoxamine 5'-phosphate (PMP).This process could explain the bathochromic shifts of the peak position in α-amino acid Schiff bases to the corresponding band in non-α-amino acid systems.
- Vazquez, M. A.,Munoz, F.,Donoso, J.,Blanco, F. Garcia
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p. 275 - 281
(2007/10/02)
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- Preparation of caprolactam
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ε-caprolactam is prepared by a process in which (a) a 5-formylvalerate is reacted with water in the presence of an acidic agent at from 30° to 200° C., (b) the 5-formylvaleric acid thus obtained is reacted with excess ammonia and hydrogen in the presence of a hydrogenation catalyst and of a solvent which is inert under the reaction conditions, at from 50° to 150° C. under superatmospheric pressure, and (c) after the ammonia has been separated off, the resulting solution of 6-aminocaproic acid is heated to 150°-370° C. and the caprolactam formed is isolated.
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