- Oxidation of L-Tyrosine by Vanadium (V) in Presence of Sulphuric Acid
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Oxidation of L-tyrosine with vanadium (V) in sulphuric acid medium at constant ionic strength is first order in oxidant and H+.The order in tyrosine varies from 1 to 0.A mechanism consistent with the kinetic results is proposed in which the rate determining step is the decomposition of the complex formed in the prior equilibrium. - Keywords: Mechanism; Oxidation; Tyrosine
- Sharma, Vijai K.,Sharma, K.,Payasi, Angad P.
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Read Online
- An enzymatic, stereoselective synthesis of (S)-norcoclaurine
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An efficient, stereoselective, green synthesis of (S)-norcoclaurine (higenamine) has been developed using the recombinant (S)-norcoclaurine synthase (NCS) enzyme, starting from the cheap tyrosine and dopamine substrates in a one-pot, two step process. Key steps in the biotransformation consist of the oxidative decarboxylation of tyrosine by stoichiometric amounts of sodium hypochlorite in order to generate 4-hydroxyphenylacetadehyde, followed by the addition of enzyme and dopamine substrate in the presence of ascorbate, a necessary ingredient in order to avoid oxidation of the catechol moiety. Quantitative extraction of the product from an aqueous solution was achieved by adsorption onto active charcoal dispersed in the reaction mixture. The optimized process afforded enantiomerically pure (S)-norcoclaurine (93%) in a yield higher than 80% and allowed good recovery of the enzyme for recycling. The process thus developed represents the first example of a green Pictet-Spengler synthesis, which may pave the way to novel strategies in benzylisoquinoline alkaloid synthesis.
- Bonamore, Alessandra,Rovardi, Irene,Gasparrini, Francesco,Baiocco, Paola,Barba, Marco,Molinaro, Carmela,Botta, Bruno,Boffi, Alberto,MacOne, Alberto
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Read Online
- Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates
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Biomass-derived hydroxycinnamates (mainly includingp-coumaric acid and ferulic acid), which are natural sources of aromatic compounds, are highly underutilized resources. There is a need to upgrade them to make them economically feasible. Value-added phenolic glycosides and their derivatives, both belonging to a class of plant aromatic natural products, are widely used in the nutraceutical, pharmaceutical, and cosmetic industries. However, their complex aromatic structures make their efficient biosynthesis a challenging process. To overcome this issue, we created three novel synthetic cascades for the biosynthesis of phenolic glycosides (gastrodin, arbutin, and salidroside) and their derivatives (hydroquinone, tyrosol, hydroxytyrosol, and homovanillyl alcohol) fromp-coumaric acid and ferulic acid. Moreover, because the biomass-derived hydroxycinnamates directly provided aromatic units, the cascades enabled efficient biosynthesis. We achieved substantially high production rates (up to or above 100-fold enhancement) relative to the glucose-based biosynthesis. Given the ubiquity of the aromatic structure in natural products, the use of biomass-derived aromatics should facilitate the rapid biosynthesis of numerous aromatic natural products.
- Zhao, Mingtao,Hong, Xulin,Abdullah,Yao, Ruilian,Xiao, Yi
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p. 838 - 847
(2021/02/09)
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- Small-molecular boron drug and application thereof
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The invention discloses a small-molecular boron drug. The small-molecular boron drug has a structure as shown in a formula I that is described in the specification. In the formula I, R is any one selected from the group consisting of ortho-carborane, meta
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Paragraph 0020-0025
(2021/07/24)
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- Biomimetic synthesis and anti-inflammatory effects of horsfiequinone A
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Inspired by the oxy-tyrosinase type II copper enzyme, a biomimetic synthesis of the natural product horsfiequinone A (1) has been achieved using CuOTf/DBED/O2 catalyzed oxidation as a key step. The synthetic route furnished 1 in 33% overall yield (64% brsm) from commercially available para-hydroxybenzaldehyde. Moreover, revisiting the biological activity of 1 resulted in the discovery of its in vitro inhibitory activity towards nitric oxide (NO) production in LPS-induced RAW264.7 cells with an IC50 value of 4.42 ± 0.81 μM. The anti-inflammatory effect of 1 was further supported by an iNOS expression inhibition assay and molecular docking simulation.
- Wang, Mei,Liu, Yuan-Lie,Li, Dashan,Xiao, Wen-Wen,Chen, Yang,Zhang, Hong-Lin,Zhan, Rui,Shao, Li-Dong
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- Efficient Synthesis of Phenylacetate and 2-Phenylethanol by Modular Cascade Biocatalysis
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The green and sustainable synthesis of chemicals from renewable feedstocks by a biotransformation approach has gained increasing attention in recent years. In this work, we developed enzymatic cascades to efficiently convert l-phenylalanine into 2-phenylethanol (2-PE) and phenylacetic acid (PAA), l-tyrosine into tyrosol (p-hydroxyphenylethanol, p-HPE) and p-hydroxyphenylacetic acid (p-HPAA). The enzymatic cascade was cast into an aromatic aldehyde formation module, followed by an aldehyde reduction module, or aldehyde oxidation module, to achieve one-pot biotransformation by using recombinant Escherichia coli. Biotransformation of 50 mM l-Phe produced 6.76 g/L PAA with more than 99 % conversion and 5.95 g/L of 2-PE with 97 % conversion. The bioconversion efficiencies of p-HPAA and p-HPE from l-Tyr reached to 88 and 94 %, respectively. In addition, m-fluoro-phenylalanine was further employed as an unnatural aromatic amino acid substrate to obtain m-fluoro-phenylacetic acid; '96 % conversion was achieved. Our results thus demonstrated high-yielding and potential industrial synthesis of above aromatic compounds by one-pot cascade biocatalysis.
- Mao, Zuoxi,Liu, Lijun,Zhang, Yang,Yuan, Jifeng
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p. 2676 - 2679
(2020/06/03)
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- MASP-2 INHIBITORS AND METHODS OF USE
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The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds and methods of making and using such compounds.
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Paragraph 2124-2125
(2019/12/24)
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- Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids
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The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher-yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non-natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non-natural alkaloids, in cascades from l-tyrosine and analogues.
- Wang, Yu,Tappertzhofen, Nadine,Méndez-Sánchez, Daniel,Bawn, Maria,Lyu, Boyu,Ward, John M.,Hailes, Helen C.
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p. 10120 - 10125
(2019/06/27)
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- Transaminase-Catalyzed Continuous Synthesis of Biogenic Aldehydes
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The physiological role of biogenic aldehydes, such as 3,4-dihydroxyphenylacetaldehyde (DOPAL), has been associated with cardiovascular and neurodegenerative disorders. The availability of these substrates is limited and robust synthetic methodologies would greatly facilitate further biological studies. Herein, a transaminase-mediated single-step process in continuous mode, which leads to excellent product yields (90–95 %), is reported. Coimmobilization of the pyridoxal phosphate (PLP) cofactor eliminated the need for exogenous addition of this reagent without affecting the longevity of the system, delivering a truly self-sufficient process.
- Contente, Martina L.,Paradisi, Francesca
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p. 2830 - 2833
(2019/08/12)
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- Selective oxidation of aliphatic C-H bonds in alkylphenols by a chemomimetic biocatalytic system
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Selective oxidation of aliphatic C-H bonds in alkylphenols serves significant roles not only in generation of functionalized intermediates that can be used to synthesize diverse downstream chemical products, but also in biological degradation of these environmentally hazardous compounds. Chemo-, regio-, and stereoselectivity; controllability; and environmental impact represent the major challenges for chemical oxidation of alkylphenols. Here, we report the development of a unique chemomimetic biocatalytic system originated from the Gram-positive bacterium Corynebacterium glutamicum. The system consisting of CreHI (for installation of a phosphate directing/ anchoring group), CreJEF/CreG/CreC (for oxidation of alkylphenols), and CreD (for directing/anchoring group offloading) is able to selectively oxidize the aliphatic C-H bonds of p-And m-Alkylated phenols in a controllable manner. Moreover, the crystal structures of the central P450 biocatalyst CreJ in complex with two representative substrates provide significant structural insights into its substrate flexibility and reaction selectivity.
- Du, Lei,Dong, Sheng,Zhang, Xingwang,Jiang, Chengying,Chen, Jingfei,Yao, Lishan,Wang, Xiao,Wan, Xiaobo,Liu, Xi,Wangi, Xinquan,Huang, Shaohua,Cui, Qiu,Feng, Yingang,Liu, Shuang-Jiang,Li, Shengying
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p. E5129 - E5137
(2017/07/04)
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- Compositions and methods for producing benzylisoquinoline alkaloids
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The present invention relates to host cells that produce compounds that are characterized as benzylisoquinolines, as well as select precursors and intermediates thereof. The host cells comprise one, two or more heterologous coding sequences wherein each of the heterologous coding sequences encodes an enzyme involved in the metabolic pathway of a benzylisoquinoline, or its precursors or intermediates from a starting compound. The invention also relates to methods of producing the benzylisoquinoline, as well as select precursors and intermediates thereof by culturing the host cells under culture conditions that promote expression of the enzymes that produce the benzylisoquinoline or precursors or intermediates thereof.
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Page/Page column 4
(2016/05/19)
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- α-Amino Acid-Isosteric α-Amino Tetrazoles
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The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field.
- Zhao, Ting,Kurpiewska, Katarzyna,Kalinowska-T?us?cik, Justyna,Herdtweck, Eberhardt,D?mling, Alexander
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supporting information
p. 3009 - 3018
(2016/03/26)
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- Polyalkylene Polymer Compounds and Uses Thereof
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The invention relates to novel polyalkylene glycol compounds and methods of using them. In particular, compounds comprising a novel polyethylene glycol conjugate are used alone, or in combination with antiviral agents to treat a viral infection, such as c
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Paragraph 0571; 0572
(2015/05/26)
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- Multicomponent synthesis of novel coelenterazine derivatives substituted at the C-3 position
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Three novel coelenterazine derivatives substituted at the C-3 position were synthesized through a multicomponent strategy based on Groebke-Blackburn-Bienaymé reaction without using protecting groups. An efficient one-pot tert-butyl group cleavage from an
- Vece, Vito,Vuocolo, Giuseppina
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p. 8781 - 8785
(2015/10/28)
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- ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
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Page/Page column 204
(2015/11/10)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
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The present invention concerns a compound of following formula (I): where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: ■ a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR5R6, ■ -(CH2CH2X1)(CH2CH2X2)a2(CH2CH2X3)a3(CH2CH2X4)a4(CH2CH2X5)a5R7, ■ an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or ■ a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 107
(2014/11/13)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
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The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 62; 63
(2014/11/13)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
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The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: - an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or - a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 79; 80
(2014/11/13)
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- Facile one-pot synthesis of tetrahydroisoquinolines from amino acids via hypochlorite-mediated decarboxylation and Pictet-Spengler condensation
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A convenient method for oxidative decarboxylation of α-amino acids is presented. The aldehyde products may be isolated or converted to tetrahydroisoquinolines by addition of dopamine via Pictet-Spengler reaction. Racemic products are generated by phosphate buffer >300 mM to maximize regioselectivity. (S)-Enantiomer products are generated by norcoclaurine synthase reaction in maleic acid buffer to minimize chemical background reaction.
- Maresh, Justin J.,Crowe, Sean O.,Ralko, Arthur A.,Aparece, Mark D.,Murphy, Casey M.,Krzeszowiec, Mark,Mullowney, Michael W.
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supporting information
p. 5047 - 5051
(2015/01/09)
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- A multi-omics strategy resolves the elusive nature of alkaloids in Podophyllum species
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Podophyllum hexandrum and, to a much lesser extent P. peltatum, are sources of podophyllotoxin, extensively used as a chemical scaffold for various anti-cancer drugs. In this study, integrated omics technologies (including advanced mass spectrometry/metabolomics, transcriptome sequencing/gene assemblies, and bioinformatics) gave unequivocal evidence that both plant species possess a hitherto unknown aporphine alkaloid metabolic pathway. Specifically, RNA-seq transcriptome sequencing and bioinformatics guided gene assemblies/analyses in silico suggested presence of transcripts homologous to genes encoding all known steps in aporphine alkaloid biosynthesis. A comprehensive metabolomics analysis, including UPLC-TOF-MS and MALDI-MS imaging in situ, then enabled detection, identification, localization and quantification of the aporphine alkaloids, magnoflorine, corytuberine and muricinine, in the underground and aerial tissues. Interestingly, the purported presence of alkaloids in Podophyllum species has been enigmatic since the 19th century, remaining unresolved until now. The evolutionary and phylogenetic ramifications of this discovery are discussed. This journal is
- Marques, Joaquim V.,Dalisay, Doralyn S.,Yang, Hong,Lee, Choonseok,Davin, Laurence B.,Lewis, Norman G.
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p. 2838 - 2849
(2015/01/08)
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- Characterization of a new enzyme oxidizing ω-amino group of aminocarboxyric acid, aminoalcohols and amines from Phialemonium sp. AIU 274
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A new enzyme exhibiting oxidase activity for ω-aminocarboxylic acids, ω-aminoalcohols, monoamines and diamines was found from a newly isolated fungal strain, Phialemonium sp. AIU 274. The enzyme also oxidized aromatic amines, but not l- and d-amino acids. The Vmax/Km value for hexylamine was higher than those for 6-aminoalcohol and 6-aminhexanoic acid in the aliphatic C6 substrates. In the aliphatic amines, the higher Vmax/Km values were obtained by the longer carbon chain amines. Thus, the enzyme catalyzed oxidative deamination of the ω-amino group in a wide variety of the ω-amino compounds and preferred medium- and long-chain substrates. The oxidase with such broad substrate specificity was first reported here. The enzyme contained copper, and the enzyme activity was strongly inhibited by isoniazid, iproniazid and semicarbazide, but not by clorgyline and pargyline. The enzyme was composed of two identical subunits of 75 kDa.
- Isobe, Kimiyasu,Sasaki, Tomoko,Aigami, Yuusuke,Yamada, Miwa,Kishino, Shigenobu,Ogawa, Jun
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- Activity-based probes for studying the activity of flavin-dependent oxidases and for the protein target profiling of monoamine oxidase inhibitors
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High profile: New activity-based protein profiling (ABPP) probes have been designed that target exclusively monoamine oxidases A and B within living cells (see picture; FAD=flavin adenine dinucleotide, FMN=flavin monodinucleotide). With these probes it could be shown that the MAO inhibitor deprenyl, which is in clinical use against Parkinson's disease, shows unique protein specificity despite its covalent mechanism of action. Copyright
- Krysiak, Joanna M.,Kreuzer, Johannes,MacHeroux, Peter,Hermetter, Albin,Sieber, Stephan A.,Breinbauer, Rolf
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supporting information; experimental part
p. 7035 - 7040
(2012/10/08)
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- Selective switchable iron-catalyzed hydrosilylation of carboxylic acids
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Selective reduction of carboxylic acids either to aldehydes or alcohols is achieved using a one pot procedure based on iron-catalyzed hydrosilylations. Using phenylsilane and (COD)Fe(CO)3 catalyst under UV-irradiation at rt, alcohols were obtained specifically in good yields, whereas aldehydes were selectively obtained using TMDS and (t-PBO)Fe(CO)3 catalyst under thermal activation.
- Misal Castro, Luis C.,Li, Haoquan,Sortais, Jean-Baptiste,Darcel, Christophe
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supporting information
p. 10514 - 10516,3
(2020/09/02)
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- Biochemical evaluation of a parsley tyrosine decarboxylase results in a novel 4-hydroxyphenylacetaldehyde synthase enzyme
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Plant aromatic amino acid decarboxylases (AAADs) are effectively indistinguishable from plant aromatic acetaldehyde syntheses (AASs) through primary sequence comparison. Spectroscopic analyses of several characterized AASs and AAADs were performed to look for absorbance spectral identifiers. Although this limited survey proved inconclusive, the resulting work enabled the reevaluation of several characterized plant AAS and AAAD enzymes. Upon completion, a previously reported parsley AAAD protein was demonstrated to have AAS activity. Substrate specificity tests demonstrate that this novel AAS enzyme has a unique substrate specificity towards tyrosine (km 0.46. mM) and dopa (km 1.40. mM). Metabolite analysis established the abundance of tyrosine and absence of dopa in parsley extracts. Such analysis indicates that tyrosine is likely to be the sole physiological substrate. The resulting information suggests that this gene is responsible for the in vivo production of 4-hydroxyphenylacetaldehyde (4-HPAA). This is the first reported case of an AAS enzyme utilizing tyrosine as a primary substrate and the first report of a single enzyme capable of producing 4-HPAA from tyrosine.
- Torrens-Spence, Michael P.,Gillaspy, Glenda,Zhao, Bingyu,Harich, Kim,White, Robert H.,Li, Jianyong
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experimental part
p. 211 - 216
(2012/07/14)
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- Phosphate mediated biomimetic synthesis of tetrahydroisoquinoline alkaloids
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A one-pot synthesis of tetrahydroisoquinoline alkaloids in a phosphate buffer has been achieved, and a reaction mechanism proposed. The utilisation of mild reaction conditions readily afforded a range of isoquinolines, including norcoclaurine.
- Pesnot, Thomas,Gershater, Markus C.,Ward, John M.,Hailes, Helen C.
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supporting information; experimental part
p. 3242 - 3244
(2011/05/05)
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- Polyalkylene polymer compounds and uses thereof
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The invention relates to novel polyalkylene glycol compounds and methods of using them. In particular, compounds comprising a novel polyethylene glycol conjugate are used alone, or in combination with antiviral agents to treat a viral infection, such as c
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- Deposition of new thia-containing Schiff-base iron (III) complexes onto carbon nanotube-modified glassy carbon electrodes as a biosensor for electrooxidation and determination of amino acids
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Multiwall carbon nanotubes (MWCNTs) were used as an immobilization matrix to incorporate an Fe (III)-Schiff base complex as an electron-transfer mediator onto a glassy carbon electrode surface. First, the preheated glassy carbon was subjected to abrasive immobilization of MWCNTs by gently rubbing the electrode surface on filter paper supporting the carbon nanotubes. Second, the electrode surface was modified by casting 100 μL of an Fe (III)-complex solution (0.01 M in ACN). The cyclic voltammograms of the modified electrode in an aqueous solution displayed a pair of well-defined, stable and nearly reversible reductive oxidation redox systems with surface confined characteristics. Combinations of unique electronic and electrocatalytic properties of MWCNTs and Fe (III)-Schiff base complexes resulted in a remarkable synergistic augmentation of the response. The electrochemical behavior and stability of the modified electrode in aqueous solutions at pH 1-9 were characterized by cyclic voltammetry. The apparent electron transfer rate constant (Ks) and transfer coefficient (a) were determined by cyclic voltammetry and were approximately 7 s-1 and 0.55, respectively. The modified electrodes showed excellent catalytic activity towards the oxidation of amino acids at an unusually positive potential in acidic solution. They also displayed inherent stability at a wide pH range, fast response time, high sensitivity, low detection limit and had a remarkably positive potential oxidation of amino acids that decreased the effect of interferences in analysis. The linear concentration range, limits of detection (LOD), limits of quantization (LOQ) and relative standard deviation of the proposed sensor for the amino acid detection were 1-55,000, 1.10-13.70, 2.79-27.14 and 1.30-5.11, respectively.
- Saghatforoush, Lotfali,Hasanzadeh, Mohammad,Shadjou, Nasrin,Khalilzadeh, Balal
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experimental part
p. 1051 - 1061
(2011/04/16)
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- Chalcones: A valid scaffold for monoamine oxidases inhibitors
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A large series of substituted chalcones have been synthesized and tested in vitro for their ability to inhibit human monoamine oxidases A and B (hMAO-A and hMAO-B). While all the compounds showed hMAO-B selective activity in the micro- and nanomolar ranges, the best results were obtained in the presence of chlorine and hydroxyl or methoxyl substituents. To better understand the enzyme-inhibitor interaction and to explain the selectivity of the most active compounds toward hMAO-B, molecular modeling studies were carried out on new, high resolution, hMAO-B crystallographic structures. For the only compound that also showed activity against hMAO-A as well as low selectivity, the molecular modeling study was also performed on the hMAO-A crystallographic structure. The docking technique provided new insight on the inhibition mechanism and the rational drug design of more potent/selective hMAO inhibitors based on the chalcone scaffold.
- Chimenti, Franco,Fioravanti, Rossella,Bolasco, Adriana,Chimenti, Paola,Secci, Daniela,Rossi, Francesca,Yá?ez, Matilde,Orallo, Francisco,Ortuso, Francesco,Alcaro, Stefano
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body text
p. 2818 - 2824
(2010/01/16)
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- Determinants of substrate specificity in KdcA, a thiamin diphosphate-dependent decarboxylase
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Thiamin diphosphate-dependent decarboxylases catalyze the non-oxidative decarboxylation of 2-keto carboxylic acids. Although they display relatively low sequence similarity, and broadly different range of substrates, these enzymes show a common homotetrameric structure. Here we describe a kinetic characterization of the substrate spectrum of a recently identified member of this class, the branched chain 2-keto acid decarboxylase (KdcA) from Lactococcus lactis. In order to understand the structural basis for KdcA substrate recognition we developed a homology model of its structure. Ser286, Phe381, Val461 and Met358 were identified as residues that appeared to shape the substrate binding pocket. Subsequently, site-directed mutagenesis was carried out on these residues with a view to converting KdcA into a pyruvate decarboxylase. The results show that the mutations all lowered the Km value for pyruvate and both the S286Y and F381W variants also had greatly increased values of kcat with pyruvate as a substrate.
- Yep, Alejandra,Kenyon, George L.,McLeish, Michael J.
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p. 325 - 336
(2008/02/09)
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- Remarkable Chichibabin-type cyclotrimerisation of 3-nitrotyrosine, tyrosine and phenylalanine to 3,5-diphenylpyridine derivatives induced by hypochlorous acid
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Reaction of 3-nitrotyrosine with HOCl in aqueous phosphate buffer (pH 7.4) leads to a mixture of extractable products, including 3,5-di(4-hydroxy-3- nitrophenyl)pyridine (15% isolated yield) and 3,5-di(4-hydroxy-3-nitrophenyl)-2- (4-hydroxy-3-nitrophenylmethyl)pyridine (3%) arising by a Chichibabin-like pyridine synthesis via N-chloroimine intermediates. Under the same conditions, phenylalanine gives 3,5-diphenylpyridine in 9% isolated yield, while tyrosine leads to 3,5-di(4-hydroxyphenyl)pyridine (3%) and 3-(3-chloro-4-hydroxyphenyl)- 5-(4-hydroxyphenyl)pyridine (3%).
- Panzella,Di Donato,Comes,Napolitano,Palumbo,D'Ischia
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p. 6457 - 6460
(2007/10/03)
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- One step hair coloring compositions using salts
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A hair coloring composition comprising the following two compositions which are mixed just prior to application to the hair: (a) a composition comprising a water-soluble peroxygen oxidizing agent; and (b) a composition comprising one or more oxidative hair coloring agents selected from the group consisting of an aromatic diamine, an amino phenol, a naphthol, a polyhydric phenol, a catechol and mixtures thereof; wherein the composition comprising one or more oxidative hair coloring agents further comprises al least one water soluble carbonate releasing salts; and optionally a water soluble ammonium salt, is described.
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- One-pot synthesis of 6-hydroxyisochromans: The example of demethyl-oxa-coclaurine
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Using a modified oxa-Pictet Spengler reaction that we recently described, we synthesized 6-hydroxy-isochromans and their 7-hydroxy derivatives. The successful one step synthesis did not require protecting groups and provided high yields. The obtainment of 1-(4′ -hydroxybenzyl)-6,7-dihydroxyisochroman (1) indicates that this protocol can be used to synthesize oxygenated analogues of benzyl-tetrahydroisoquinoline alkaloids, such as demethyl-coclaurine (2). This methodology could provide a general procedure for the synthesis of hydroxyisochromans. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Guiso, Marcella,Bianco, Armandodoriano,Marra, Carolina,Cavarischia, Claudia
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p. 3407 - 3411
(2007/10/03)
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- Probing crucial metabolic pathways in fungal pathogens of crucifers: Biotransformation of indole-3-acetaldoxime, 4-hydroxyphenylacetaldoxime, and their metabolites
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Indole-3-acetaldoxime is an intermediate of crucial importance in the biosynthesis of diverse plant secondary metabolites of Cruciferae. The metabolism of indole-3-acetaldoxime to indole-3-acetic acid via indole-3-acetonitrile by fungi that cause important plant diseases in crucifers, Leptosphaeria maculans (asexual stage Phoma lingam) causative agent of blackleg disease, Rhizoctonia solani causative agent of root rot disease, and Sclerotinia sclerotiorum causative agent of stem rot disease, is described. As well, the antifungal activity of indole-3-acetaldoxime and metabolites and the synthesis and biotransformation of 4-hydroxyphenylacetaldoxime by the same plant pathogens and by an insect fungal pathogen, Beauveria bassiana, are reported.
- Pedras, M. Soledade C.,Montaut, Sabine
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p. 3115 - 3120
(2007/10/03)
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- Transition metal complexes as dye forming catalysts in hair coloring compositions
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A hair coloring composition comprising a first composition which comprises: (a) a dye forming transition metal salt or complex; which is first applied to the hair; and a second composition which comprises the following two compositions which are mixed just prior to application to the hair: (a) a composition comprising a water-soluble peroxygen oxidizing agent; and (b) a composition comprising one or more oxidative hair coloring agents selected from the group consisting of an aromatic diamine, an aminophenol, a polyhydric phenol a catechol and mixtures thereof.
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- Total syntheses of kurasoins A and B, novel protein farnesyltransferase inhibitors, and absolute structures of kurasoins A and B
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Asymmetric total syntheses of kurasoins A (1) and B (2), recently discovered protein farnesyltransferase (PFTase) inhibitors, have been achieved in seven steps from 2-(4-hydroxyphenyl)ethanol via the stereospecific alkylation of the chiral epoxide ((-)-7) and in four steps from phenylacetaldehyde via the coupling reaction of the chiral epoxide ((-)- 13) with indole, respectively. The synthesis defined the (3S) absolute configuration of 1 and 2. The stereochemistry of the hydroxy group is important for eliciting PFTase inhibition.
- Hirose, Tomoyasu,Sunazuka, Toshiaki,Zhi-Ming, Tian,Handa, Masaki,Uchida, Ryuji,Shiomi, Kazuro,Harigaya, Yoshihiro,Omura, Satoshi
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p. 777 - 784
(2007/10/03)
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- ASYMMETRIC SYNTHESIS OF THE ANTICOCCIDIAL ANTIBIOTIC DIOLMYCIN A1. DETERMINATION OF ABSOLUTE STEREOCHEMISTRY
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An asymmetric total synthesis of diolmycin A1 (1), a recently discovered anticoccidial antibiotic, has been achieved in six steps from 2-(4-hydroxyphenyl)ethanol.The natural product comprises an unusual ca. 4:1 mixture of enantiomers; the synthesis defined the (11R,12S) absolute configuration of the predominant (-) antipode.
- Sunazuka, Toshiaki,Tabata, Noriko,Nagamitsu, Tohru,Tomoda, Hiroshi,Omura, Satoshi,Smith, Amos B.
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p. 6659 - 6660
(2007/10/02)
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- Intramolecular Cyclopropanation Reaction of Furanyl Diazo Ketones
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α-Diazo ketones derived from furanyl- and benzofuranylpropionic acids were prepared, and their rhodium(II) acetate catalyzed behavior was studied.The results are consistent with a mechanism in which the key step involves addition of a keto carbenoid intermediate on to the furanyl ?-bond followed by an electrocyclic ring-opening reaction.In the case of the benzo-substituted furanyl system, the suspected bicyclic intermediate was isolated in high yield and its chemistry was subsequently investigated.The bicyclic ketone derived from 1-diazo-4-(2-benzofuryl)-2-butanone undergoes a novel thermal rearrangement to a benzopyranone derivative.This unexpected transformation can be rationalized in terms of a -cycloreversion reaction to give an ortho-quinoidal intermediate, which undergoes a subsequent electrocyclic ring closure followed by a 1,3-hydrogen shift.Furans with side chains of various lengths containing a diazomethyl keto group were also studied.The cyclization chemistry of the closely related diazothienylalkanone system was investigated and found to give products derived from an analogous intramolecular cyclopropanation reaction.
- Padwa, Albert,Wisnieff, Thomas J.,Walsh, Edward J.
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p. 299 - 308
(2007/10/02)
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- Synthesis of Cycloalkenones via the Intramolecular Cyclopropanation of Furanyl Diazo Ketones
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The reaction of α-diazo ketones derived from furanyl and benzofuranyl propionic acids with rhodium(II) acetate leads to cycloalkenones in high yield.Mechanistically,, the reaction involves addition of the keto carbene to the furanyl ?-bond followed by ele
- Padwa, Albert,Wisnieff, Thomas J.,Walsh, Edward J.
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p. 5036 - 5038
(2007/10/02)
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- Enzyme-activated oxidative process for coloring hair
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An enzyme-based oxidative process for coloring hair wherein the hair is exposed to a solution having a pH of about 4 to about 10 and containing hydrogen peroxide, soybean peroxidase enzyme and one or more oxidation dye precursors.
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