- Photoinduced homolytic decarboxylative acylation/cyclization of unactivated alkenes with α-keto acid under external oxidant and photocatalyst free conditions: access to quinazolinone derivatives
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A novel and green strategy for the synthesis of acylated quinazolinone derivativesviaphoto-induced decarboxylative cascade radical acylation/cyclization of quinazolinone bearing unactivated alkenes has been developed. The protocol provides a novel route to access acyl radicals from α-keto acids through a self-catalyzed energy transfer process. Most importantly, the reaction proceeded smoothly without any external photocatalyst, additive or oxidant, and could be easily scaled-up in flow conditions with sunlight irradiation.
- Sun, Bin,Shi, Rongcheng,Zhang, Kesheng,Tang, Xiaoli,Shi, Xiayue,Xu, Jiayun,Yang, Jin,Jin, Can
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supporting information
p. 6050 - 6053
(2021/06/21)
-
- Chemoenzymatic Production of Enantiocomplementary 2-Substituted 3-Hydroxycarboxylic Acids from l-α-Amino Acids
-
A two-enzyme cascade reaction plus in situ oxidative decarboxylation for the transformation of readily available canonical and non-canonical l-α-amino acids into 2-substituted 3-hydroxycarboxylic acid derivatives is described. The biocatalytic cascade consisted of an oxidative deamination of l-α-amino acids by an l-α-amino acid deaminase from Cosenzaea myxofaciens, rendering 2-oxoacid intermediates, with an ensuing aldol addition reaction to formaldehyde, catalyzed by metal-dependent (R)- or (S)-selective carboligases namely 2-oxo-3-deoxy-l-rhamnonate aldolase (YfaU) and ketopantoate hydroxymethyltransferase (KPHMT), respectively, furnishing 3-substituted 4-hydroxy-2-oxoacids. The overall substrate conversion was optimized by balancing biocatalyst loading and amino acid and formaldehyde concentrations, yielding 36–98% aldol adduct formation and 91–98% ee for each enantiomer. Subsequent in situ follow-up chemistry via hydrogen peroxide-driven oxidative decarboxylation afforded the corresponding 2-substituted 3-hydroxycarboxylic acid derivatives. (Figure presented.).
- Pickl, Mathias,Marín-Valls, Roser,Joglar, Jesús,Bujons, Jordi,Clapés, Pere
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p. 2866 - 2876
(2021/04/14)
-
- Targeted Covalent Inhibition of Plasmodium FK506 Binding Protein 35
-
FK506-binding protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects. In contrast to human FKBPs, FKBP35 contains a cysteine, C106, adjacent to the rapamycin binding pocket, providing an opportunity to develop targeted covalent inhibitors of Plasmodium FKBP35. Here, we synthesize inhibitors of FKBP35, show that they directly bind FKBP35 in a model cellular setting, selectively covalently modify C106, and exhibit antiplasmodium activity in blood-stage cultured parasites.
- Atack, Thomas C.,Raymond, Donald D.,Blomquist, Christa A.,Pasaje, Charisse Flerida,McCarren, Patrick R.,Moroco, Jamie,Befekadu, Henock B.,Robinson, Foxy P.,Pal, Debjani,Esherick, Lisl Y.,Ianari, Alessandra,Niles, Jacquin C.,Sellers, William R.
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supporting information
p. 2131 - 2138
(2020/12/17)
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- Synthesis method of 2-(9H-fluorene-9-methoxycarbonylamino)-3-methyl-2-butenoic acid
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The invention relates to a synthesis method of 2-(9H-fluorene-9-methoxycarbonylamino)-3-methyl-2-butenoic acid. The method mainly solves the technical problem of lack of an amplified production methodof 2-(9H-fluorene-9-methoxycarbonylamino)-3-methyl-2-butenoic acid at present. The synthesis method comprises the following steps: in methyl tert-butyl ether cooled in an ice bath, acidifying 3-methyl-2-oxobutyrate with concentrated hydrochloric acid to generate a compound 1; in methylbenzene subjected to heating reflux, the compound 1 and fluorenylmethoxycarbonylamide are subjected to dehydration condensation reaction under the catalytic action of p-toluenesulfonic acid to generate a target compound 2. As a medical intermediate and a dehydroamino acid derivative, 2-(9H-fluorene-9-methoxycarbonylamino)-3-methyl-2-butenoic acid is widely applied to the fields of synthesis of peptide active substances and protein engineering.
- -
-
Paragraph 0006; 0009
(2020/12/30)
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- Exploration of Transaminase Diversity for the Oxidative Conversion of Natural Amino Acids into 2-Ketoacids and High-Value Chemicals
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The use of 2-ketoacids is very common in feeds, food additives, and pharmaceuticals, and 2-ketoacids are valuable precursors for a plethora of chemically diverse compounds. Biocatalytic synthesis of 2-ketoacids starting from l-amino acids would be highly desirable because the substrates are readily available from biomass feedstock. Here, we report bioinformatic exploration of a series of aminotransferases (ATs) to achieve the desired conversion. Thermodynamic control was achieved by coupling an l-glutamate oxidation reaction in the cascade for the recycling of the amine acceptor. These enzymes were able to convert a majority of proteinogenic amino acids into the corresponding 2-ketoacids with high conversion (up to 99percent) and atom-efficiency. Furthermore, this enzyme cascade was extendable, and one-pot two-step processes were established for the synthesis of d-amino acids and N-methylated amino acids, achieving great overall conversion (up to 99percent) and high ee values (>99percent). These developed enzymatic methodologies offer convenient routes for utilizing amino acids as synthetic reagents.
- Chen, Yanchun,Cui, Xuexian,Cui, Yinglu,Li, Chuijian,Li, Ruifeng,Li, Tao,Sun, Jinyuan,Wu, Bian,Zhu, Tong
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p. 7950 - 7957
(2020/08/21)
-
- Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine Derivatives and Structure Revision of Thelepamide
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The first enantioselective total synthesis and structural reassignment of (-)-thelepamide, a cytotoxic tetraketide-amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre's organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal-hemiacetal moiety. The corrected structure was confirmed by NMR-DFT analysis.
- Seitz, Tobias,Millán, Ramón E.,Lentz, Dieter,Jiménez, Carlos,Rodríguez, Jaime,Christmann, Mathias
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supporting information
p. 594 - 597
(2018/02/10)
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- The pseudoalteromonas luteoviolacea L-amino acid oxidase with antimicrobial activity is a flavoenzyme
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The marine environment is a rich source of antimicrobial compounds with promising pharmaceutical and biotechnological applications. The Pseudoalteromonas genus harbors one of the highest proportions of bacterial species producing antimicrobial molecules. For decades, the presence of proteins with L-amino acid oxidase (LAAO) and antimicrobial activity in Pseudoalteromonas luteoviolacea has been known. Here, we present for the first time the identification, cloning, characterization and phylogenetic analysis of Pl-LAAO, the enzyme responsible for both LAAO and antimicrobial activity in P. luteoviolacea strain CPMOR-2. Pl-LAAO is a flavoprotein of a broad substrate range, in which the hydrogen peroxide generated in the LAAO reaction is responsible for the antimicrobial activity. So far, no protein with a sequence similarity to Pl-LAAO has been cloned or characterized, with this being the first report on a flavin adenine dinucleotide (FAD)-containing LAAO with antimicrobial activity from a marine microorganism. Our results revealed that 20.4% of the sequenced Pseudoalteromonas strains (specifically, 66.6% of P. luteoviolacea strains) contain Pl-laao similar genes, which constitutes a well-defined phylogenetic group. In summary, this work provides insights into the biological significance of antimicrobial LAAOs in the Pseudoalteromonas genus and shows an effective approach for the detection of novel LAAOs, whose study may be useful for biotechnological applications.
- Andreo-Vidal, Andrés,Sanchez-Amat, Antonio,Campillo-Brocal, Jonatan C.
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- Asymmetric C-Alkylation by the S-Adenosylmethionine-Dependent Methyltransferase SgvM
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S-Adenosylmethionine-dependent methyltransferases (MTs) play a decisive role in the biosynthesis of natural products and in epigenetic processes. MTs catalyze the methylation of heteroatoms and even of carbon atoms, which, in many cases, is a challenging reaction in conventional synthesis. However, C-MTs are often highly substrate-specific. Herein, we show that SgvM from Streptomyces griseoviridis features an extended substrate scope with respect to the nucleophile as well as the electrophile. Aside from its physiological substrate 4-methyl-2-oxovalerate, SgvM catalyzes the (di)methylation of pyruvate, 2-oxobutyrate, 2-oxovalerate, and phenylpyruvate at the β-carbon atom. Chiral-phase HPLC analysis revealed that the methylation of 2-oxovalerate occurs with R selectivity while the ethylation of 2-oxobutyrate with S-adenosylethionine results in the S enantiomer of 3-methyl-2-oxovalerate. Thus SgvM could be a valuable tool for asymmetric biocatalytic C-alkylation reactions.
- Sommer-Kamann, Christina,Fries, Alexander,Mordhorst, Silja,Andexer, Jennifer N.,Müller, Michael
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supporting information
p. 4033 - 4036
(2017/03/27)
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- ENZYMATIC METHODS FOR ISOBUTANOL PRODUCTION
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The present invention relates to a process of producing isobutanol, including: mixing water, lactate, an enzyme mixture including at least one enzyme, at least one cofactor, and at least one coenzyme, to prepare a reaction mixture; allowing catalytic conversions of lactate in the reaction mixture for a sufficient amount of time to produce isobutanol; and separating the isobutanol from a reactant obtained by the catalytic conversions, in which the conversion of lactate into isobutanol is in association with a NAD+/NADH and/or NADP+/NADPH regenerating system.
- -
-
Paragraph 00148-00152
(2016/07/05)
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- A kind of the α-ketone valine process for preparing calcium
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The invention relates to a new preparation technology of alpha-ketone valine calcium, and belongs to the technical field of medicine synthesis. According to the new preparation technology of the alpha-ketone valine calcium, oxygen in the air is used as an oxidant, alpha-valine is catalytically oxidized in situ into alpha-ketone valine by N-heterocyclic imidazolium salt, and the alpha-ketone valine calcium is obtained by neutralization reaction of the alpha-ketone valine. According to the new preparation technology, the alpha-ketone valine calcium is obtained mainly by catalytic oxidation, the product yield is up to 87.5%, the purity is up to 99.7%, the technical scheme of the new preparation technology is relatively mild in reaction conditions, high in process yield, and suitable for large scale production.
- -
-
Paragraph 0029; 0031; 0032
(2017/01/12)
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- Cationic Ir/Me-BIPAM-catalyzed asymmetric intramolecular direct hydroarylation of α-ketoamides
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Asymmetric intramolecular direct hydroarylation of α-ketoamides gives various types of optically active 3-substituted 3-hydroxy-2-oxindoles in high yields with complete regioselectivity and high enantioselectivities (84-98 % ee). This is realized by the use of the cationic iridium complex [Ir(cod) 2](BArF4) and the chiral O-linked bidentate phosphoramidite (R,R)-Me-BIPAM. Carbon's got a brand new bond: Asymmetric intramolecular direct hydroarylation of α-ketoamides gives various optically active 3-substituted 3-hydroxy-2-oxindoles in high yields with complete regioselectivity and high enantioselectivities. This is realized by the use of an asymmetric cationic iridium complex formed in situ (see Scheme).
- Shirai, Tomohiko,Ito, Hajime,Yamamoto, Yasunori
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supporting information
p. 2658 - 2661
(2014/03/21)
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- Stereoselective synthesis of l-tert-leucine by a newly cloned leucine dehydrogenase from Exiguobacterium sibiricum
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A leucine dehydrogenase from Exiguobacterium sibiricum (EsLeuDH) was discovered by genome mining approach. The EsLeuDH was overexpressed in Escherichia coli BL21, purified to homogeneity and characterized. This enzyme showed good thermostability with a half-life of 3.1 h at 60 °C. Furthermore, EsLeuDH has a broad spectrum of substrate specificity, showing activities toward many aliphatic α-keto acids and L-amino acids, in addition to some aryl α-keto acids and aryl α-amino acids, such as α-oxobenzeneacetic and l-phenylglycine. The EsLeuDH was successfully coexpressed with Bacillus megaterium glucose dehydrogenase (BmGDH) in Escherichia coli BL21 for the production of l-tert-leucine. By using the coexpressed whole cells, a decagram preparation of l-tert-leucine was performed at a substrate concentration of 0.6 M (78.1 g L-1) in 1 L scale with 99% conversion after 5.5 h, resulting in 80.1% yield and > 99% ee (enantiomeric excess).2014 Published by Elsevier B.V.
- Li, Jing,Pan, Jiang,Zhang, Jie,Xu, Jian-He
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-
- Characterization of d-amino acid aminotransferase from Lactobacillus salivarius
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We searched a UniProt database of lactic acid bacteria in an effort to identify d-amino acid metabolizing enzymes other than alanine racemase. We found a d-amino acid aminotransferase (d-AAT) homologous gene (UniProt ID: Q1WRM6) in the genome of Lactobacillus salivarius. The gene was then expressed in Escherichia coli, and its product exhibited transaminase activity between d-alanine and α-ketoglutarate. This is the first characterization of a d-AAT from a lactic acid bacterium. L. salivarius d-AAT is a homodimer that uses pyridoxal-5′-phosphate (PLP) as a cofactor; it contains 0.91 molecules of PLP per subunit. Maximum activity was seen at a temperature of 60 °C and a pH of 6.0. However, the enzyme lost no activity when incubated for 30 min at 30 °C and pH 5.5 to 9.5, and retained half its activity when incubated at pH 4.5 or 11.0 under the same conditions. Double reciprocal plots of the initial velocity and d-alanine concentrations in the presence of several fixed concentrations of α-ketoglutarate gave a series of parallel lines, which is consistent with a Ping-Pong mechanism. The Km values for d-alanine and α-ketoglutarate were 1.05 and 3.78 mM, respectively. With this enzyme, d-allo-isoleucine exhibited greater relative activity than d-alanine as the amino donor, while α-ketobutylate, glyoxylate and indole-3-pyruvate were all more preferable amino acceptors than α-ketoglutarate. The substrate specificity of L. salivarius d-AAT thus differs greatly from those of the other d-AATs so far reported.
- Kobayashi, Jyumpei,Shimizu, Yasuhiro,Mutaguchi, Yuta,Doi, Katsumi,Ohshima, Toshihisa
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- Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids
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Flee to the hills: An unfavorable equilibrium in the amino group transfer between amino acids and keto acids catalyzed by α-transaminases was successfully overcome by coupling with a ω-transaminase reaction as an equilibrium shifter, leading to efficient asymmetric synthesis of diverse unnatural amino acids, including L-tert-leucine and D-phenylglycine. Copyright
- Park, Eul-Soo,Dong, Joo-Young,Shin, Jong-Shik
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p. 3538 - 3542
(2014/01/06)
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- Mutant d-amino acid oxidase with higher catalytic efficiency toward d-amino acids with bulky side chains
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d-Amino acid oxidase from the yeast Trigonopsis variabilis (TvDAAO) is widely used in fine organic synthesis, including the preparation of unnatural l-amino acids and α-keto acids. The analysis of the three-dimensional structure of TvDAAO was carried out with the aim of producing the enzyme specific to d-amino acids with bulky side chains. The analysis revealed the residue Phe54 at the entrance to the active site, which controls the substrate access to this site. The residue Phe54 was replaced by residues Ala, Ser, and Tyr. The cultivation of recombinant E. coli strains expressing TvDAAO mutants showed that the mutein with the Phe54Ala substitution had very low stability. Thus, the inactivation of the enzyme occured within 10 min after the cell disruption. The Phe54Ser TvDAAO and Phe54Tyr TvDAAO mutants were obtained as homogeneous preparations, and their thermal stability and catalytic properties were investigated. The introduction of Phe54Ser and Phe54Tyr substitutions resulted in additional stabilization of the protein macromolecule compared to the wild-type TvDAAO. Thus, the half-inactivation time for the mutant enzymes at 54 C increased by a factor of 1.5 and 2, respectively. As in the case of wild-type TvDAAO, the thermal inactivation of the muteins proceeds via a two-step dissociative mechanism. The introduction of mutations led to a strong change in the substrate specificity profile. The mutants have no activity toward a series of d-amino acids (Phe54Ser TvDAAO toward d-Ala, d-Ser, d-Val, and d-Thr; Phe54Tyr TvDAAO toward d-Ser, d-Tyr, d-Thr, and d-Lys). The catalytic efficiency (the k cat/K M ratio) of the Phe54Ser TvDAAO mutant toward d-amino acids with bulky side chains (d-Lys, d-Asn, d-Phe, d-Tyr, d-Trp, and d-Leu) increased from 2.4 to 7.3 times.
- Komarova,Golubev,Khoronenkova,Tishkov
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p. 1489 - 1496
(2013/11/19)
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- Role of the active site residues arginine-216 and arginine-237 in the substrate specificity of mammalian D-aspartate oxidase
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d-Aspartate oxidase (DDO) and d-amino acid oxidase (DAO) are flavin adenine dinucleotide-containing flavoproteins that catalyze the oxidative deamination of d-amino acids. Unlike DAO, which acts on several neutral and basic d-amino acids, DDO is highly specific for acidic d-amino acids. Based on molecular modeling and simulated annealing docking analyses, a recombinant mouse DDO carrying two substitutions (Arg-216 to Leu and Arg-237 to Tyr) was generated (R216L-R237Y variant). This variant and two previously constructed single-point mutants of mouse DDO (R216L and R237Y variants) were characterized to investigate the role of Arg-216 and Arg-237 in the substrate specificity of mouse DDO. The R216L-R237Y and R216L variants acquired a broad specificity for several neutral and basic d-amino acids, and showed a considerable decrease in activity against acidic d-amino acids. The R237Y variant, however, did not show any additional specificity for neutral or basic d-amino acids and its activity against acidic d-amino acids was greatly reduced. The kinetic properties of these variants indicated that the Arg-216 residue is important for the catalytic activity and substrate specificity of mouse DDO. However, Arg-237 is, apparently, only marginally involved in substrate recognition, but is important for catalytic activity. Notably, the substrate specificity of the R216L-R237Y variant differed significantly from that of the R216L variant, suggesting that Arg-237 has subsidiary effects on substrate specificity. Additional experiments using several DDO and DAO inhibitors also suggested the involvement of Arg-216 in the substrate specificity and catalytic activity of mouse DDO and that Arg-237 is possibly involved in substrate recognition by this enzyme. Collectively, these results indicate that Arg-216 and Arg-237 play crucial and subsidiary role(s), respectively, in the substrate specificity of mouse DDO.
- Katane, Masumi,Saitoh, Yasuaki,Maeda, Kazuhiro,Hanai, Toshihiko,Sekine, Masae,Furuchi, Takemitsu,Homma, Hiroshi
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experimental part
p. 467 - 476
(2011/10/05)
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- Synthesis-guided structure revision of the sarcodonin, sarcoviolin, and hydnellin natural product family
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A sweeping structural revision of the sarcodonin natural product family (published structures 1a-13a) is proposed after extensive studies aimed at their chemical synthesis. Key features of revised structure 1b include replacement of the N,N-dioxide moiety with an oxime, ring-opening of the central diketopiperazine, and transposition of the terphenyl wing from the 1β-2β position of 1a to the 2β-3β position of 1b. This structure revision arose from the serendipitous synthesis of a benzodioxane aminal (44) whose structure was unambiguously determined by X-ray crystallography and whose spectral properties bore considerable resemblance to the published data for the sarcodonins. A versatile new method for O-arylation of hydroxamic acids is also reported herein, as well as a manganese(III)- mediated α-oxidation of hydroxamic acids to aminals.
- Lin, David W.,Masuda, Takeshi,Biskup, Moritz B.,Nelson, Jonathan D.,Baran, Phil S.
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supporting information; experimental part
p. 1013 - 1030
(2011/04/15)
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- The role of residues Arg169 and Arg220 in intersubunit interactions of yeast D-Amino acid oxidase
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D-Amino acid oxidase from the yeast Trigonopsis variabilis (EC 1.4.3.3, TvDAAO) exists as a dimer consisting of two identical subunits. The dimeric structure of the enzyme is stabilized by 12 (six pairs) hydrogen bonds, the residues Arg169 and Arg220 of each subunit being involved in eight hydrogen bonds. The Arg169Glu and Arg(169,220)Ala mutants of TvDAAO were prepared. Both mutant enzymes were expressed in E. coli cells as insoluble but catalytically active inclusion bodies. The introduction of amino acid substitutions at the intersubunit interface resulted in a change in the substrate specificity profile and a strong decrease in thermal stability.
- Cherskova,Khoronenkova,Tishkov
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scheme or table
p. 269 - 275
(2011/01/06)
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- PROCESS FOR MAKING N-SULFONATED-AMINO ACID DERIVATIVES
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This invention relates to a process for preparing optically active α -amino acid substrates which are used to make potent lethal factor (LF) inhibitors for the treatment of anthrax. This invention further relates to a process for synthesis of potent LF-inhibitors for the treatment of anthrax. Specifically, the invention concerns a novel, high-yielding and highly enantioselective asymmetric hydrogenation reaction of a tetrasubstituted ene-sulfonamide acid or ester.
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Page/Page column 26-29
(2008/06/13)
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- Asymmetric hydrogenation of N-sulfonylated-α-dehydroamino acids: Toward the synthesis of an anthrax lethal factor inhibitor
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(Chemical Equation Presented) A novel and highly enantioselective Ru-catalyzed hydrogenation of N-sulfonylated-α-dehydroamino acids has been discovered and demonstrated in the synthesis of an anthrax lethal factor inhibitor (LFI). Herein, this methodology is used to prepare N-sulfonylated amino acids in up to 98% ee. This unprecedented hydrogenation uses a chiral Ru catalyst rather than Rh as typical for acylated dehydroamino acids and esters, and this work reports the first asymmetric hydrogenation of a tetrasubstituted dehydroamino acid derivative using a Ru catalyst.
- Shultz, C. Scott,Dreher, Spencer D.,Ikemoto, Norihiro,Williams, J. Michael,Grabowski, Edward J. J.,Krska, Shane W.,Sun, Yongkui,Dormer, Peter G.,DiMichele, Lisa
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p. 3405 - 3408
(2007/10/03)
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- Method for preparing chiral diphosphines
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The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.
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- Applicability of a modified Edman procedure for measurement of protein adducts: Mechanisms of formation and degradation of phenylthiohydantoins
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Adducts to N-terminal valine residues in hemoglobin (Hb) are used for monitoring in vivo doses of electrophiles and are quantitated by means of a modified Edman procedure, the "N-alkyl Edman procedure". In the reaction with pentafluorophenyl isothiocyanate, N-alkylated valines cyclize and detach from the protein as pentafluorophenylthiohydantoins (PFPTHs) much more efficiently than do unsubstituted N-terminal valine residues. The mechanisms of this reaction, and of possible degradation reactions, have been studied with model compounds using phenyl- and pentafluorophenyl isothiocyanate. The rapid cyclization to N-alkylvaline-PTHs occurs as a consequence of the influence of substituents on ring formation. This facilitated cyclization favors a direct attack by the thiocarbamoyl nitrogen atom on valine-C-1, and is also observed to occur slowly at unsubstituted N-terminal valines. Such cyclization is favored in protic solvents. Under alkaline conditions and in the presence of air, hydrolytic and oxidative processes give rise to degradation products. The PTH derivatives of N-alkylvaline are less apt to undergo such reactions than are the corresponding derivatives of unsubstituted valine. We conclude that the presence of an N-substituent exerts a greater influence on the cyclization process than the structure of the amino acid or of the Edman reagent. For adducts of different structures, the method has broad applicability, for which the limits, however, are not yet explored. The knowledge from the studies is valid not only for the N-alkyl Edman procedure, but also, to some extent, for the classical Edman degradation reaction. The oxidative side reaction gave rise to the invention of a novel synthesis route for insertion of nucleophiles at carbon-5 in thiohydantoins. The present investigation provides a basis for the N-alkyl Edman procedure, facilitating new toxicological applications.
- Rydberg, Per,Luening, Bjoern,Wachtmeister, Carl Axel,Eriksson, Lars,Toernqvist, Margareta
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p. 570 - 581
(2007/10/03)
-
- Asymmetric hydrogenation method of a ketonic compound and derivative
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The present invention relates to a process for the asymmetric hydrogenation of a ketonic compound and derivative. The invention relates to the use of optically active metal complexes as catalysts for the asymmetric hydrogenation of a ketonic compound and derivative. The process for the asymmetric hydrogenation of a ketonic compound and derivative is characterized in that the asymmetric hydrogenation of said compound is carried out in the presence of an effective amount of a metal complex comprising as ligand an optically active diphosphine corresponding to one of the following formulae: STR1
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- Concerted base-promoted elimination in the decomposition of N-halo amino acids
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N-Chloroamino acids are unstable in aqueous solution and decompose through different pathways depending on the reaction conditions, yielding precursors of carcinogenic and/or mutagenic compounds. One of these pathways is a 1,2-elimination process, which has scarcely received any attention and for which no systematic analysis is available. The process is first order relative to the N-chloroamino acid and to that of hydroxide ion. The use of 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoropropan-2-ol buffer solutions established that the process is general-base catalysed. The reaction rate is affected by the presence of a methyl group on the nitrogen atom and the nature of the leaving group. The results show an important steric effect due to the alkyl substituents on the α-carbon. With bulky alkyl substitueras on the α-carbon, and in particular in the case of N-alkylamino acids, the catalytic effect increases as the base strength decreases. To characterize the transition state, Brtonsted's β and βlg were used. A More O'Ferrall-Jencks diagram shows the transition state structure changing from carbanion-like to nitrenium-like, a large perpendicular effect being evident. The reaction proceeds through a concerted mechanism AxhDHDN instead of the stepwise AxhDH? + DN proposed earlier.
- Armesto,Canle L,Garcia,Losada,Santaballa
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p. 552 - 560
(2007/10/03)
-
- Kinetics and mechanism of oxidation of α-amino acids by Fremy's radical in aqueous borate buffer medium
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Oxidation of α-amino acids viz., glycine, alanine, phenylalanine, valine, aspartic acid, serine and threonine by Fremy's radical (potassium nitrosodisulphonate, PNDS) in aqueous-borate buffer medium at pH 10.0 shows first order dependence each on [PNDS] and [α-amino acid]. Under the experimental conditions PNDS has been found to be quite stable. However, the little'self decomposition of PNDS found on standing for longer period has been prevented by the addition of sulphamate ion. Increase in ionic strength of the medium has no effect on the rate of oxidation. The mechanism proposed involves direct attack of PNDS on α-amino acid to give an α-amino acid radical. PNDS being a very good radical trap, efficiently reacts with α-amino acid radicals to give α-keto acid via easily hydrolysable α-imino acid. The order of reactivity has been found to be phenylalanine > alanine > serine > glycine > valine > threonine > aspartic acid.
- Kawle, Baloji,Thirupathi Rao,Adinarayana
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p. 667 - 670
(2007/10/03)
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- General base catalysis in the decomposition of N-Cl-valine in aqueous solution
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This article analyzes the kinetics of the decomposition of N-Cl-Valine in aqueous solution, which is formed rapidly by chlorination of Valine with sodium hypochlorite. A general-base catalyzed process not yet described is reported. The experimental evidence shows two competitive decomposition paths: an unimolecular concerted fragmentation process (k = (1.8 ± 0.1) · 10-4 s-1 at 298 K) and the other one is an E2 elimination process whose importance increases with pH and depends on the nature and the concentration of the bases present in the medium.
- Abia,Armesto,Canle,Garcia,Losada,Santaballa
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p. 1041 - 1053
(2007/10/03)
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- 4-Isopropyl-2-oxazolin-5-one anion as a new convenient formyl anion equivalent for conjugate addition and aldol reactions
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The anion of the title compound, simply generated in the presence of catalytic amount of triethylamine, acts as nucleophilic acylating equivalent of formaldehyde reacting with both common electrophilic olefins or aldehydes to give moderate to good yield of Michael or aldol adducts respectively, which are easily hydrolized by dilute acid at ambient to temperature to afford the corresponding aldehydes.
- Barco, Achille,Benetti, Simonetta,De Risi, Carmela,Pollini, Gian P.,Spalluto, Giampiero,Zanirato, Vinicio
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p. 3907 - 3910
(2007/10/02)
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- Pharmaceuticals and dietetics containing acylamino acid derivatives
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Acylamino carboxylic acid derivatives corresponding to the formula I STR1 in which the groups R1, R2, R3, Z1 and Z2 represent functional groups specified in the claims. The acylamino carboxylic acid derivatives have valuable pharmacological properties which, in particular, favorably influence nitrogen metabolism. The compounds are useful as active ingredients in pharmaceutical and/or dietetic compositions for treatment or prevention of nitrogen metabolism disturbances in large mammals caused, for example, by liver or kidney damage.
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- Synthesis of dihydro-2,3-furandiones from diethyl oxalate and aldehydes through the action of sodium methoxide
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Dihydro-4,4-dimethyl-2,3-furandione (4e) was synthesized from diethyl oxalate, methylpropanal (1a) and formaldehyde in the presence of sodium methoxide. In a similar manner, analogs of dihydro-2,3-furandione 4 were prepared using other aldehydes.
- Hata,Morishita,Akutsu,Kawamura
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p. 289 - 291
(2007/10/02)
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- Polyfunctional (R)-2-Hydroxycarboxylic Acids by Reduction of 2-Oxo Acids with Hydrogen Gas or Formate and Resting Cells of Proteus vulgaris
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Various (R)-2-hydroxy acids such as (R)-2-hydroxy-3-enoic-, 3,5-dienoic-, 4-oxo-, (R,S)-3-hydroxy and some others were prepared on a scale up to 0.12 mol by biocatalytic reduction of the corresponding 2-oxo acids with P. vulgaris and hydrogen gas and/or formate as electron donors.With the exception of the 2-hydroxy-4-oxo acids it could be proved that the enantiomeric excess is >97 percent.For the 4-oxo derivatives this enantiomeric excess can be assumed.The yields of isolated products are high because they were isolated from rather small amounts of biocatalyst and low buffer concentrations.Product concentrations in the range of 0.1- 0.24 M were obtained.For 1 mmol of product formation in 15-20 h about 20-40 mg (dry weight) of P. vulgaris cells are necessary.
- Schummer, Anita,Yu, Hongtao,Simon, Helmut
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p. 9019 - 9034
(2007/10/02)
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- Kinetics of oxidation of amino acids by hexachloroiridate(IV) in aqueous acid medium
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The title reaction studied in the pH range of 2.5 to 3.5 is pseudo-first order in in the presence of excess .The rate increases with increase in and the order in is fractional.The rate also increases with increase in +> and the order in +> is unity.Added salts and change in dielectric constant of the medium do not affect the rate appreciably.However, added acrylamide induces polymerisation.A suitable mechanism has been proposed.
- Kumar, Ch. Sudheer,Chandraiah, U.,Siddiqui, M. A. A.,Kandlikar, Sushma
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p. 714 - 716
(2007/10/02)
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- Alternative energy substrates
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Compounds of the general formula, A - B, where A is a carboxylic acid group having a carbon chain of 3-10 carbon atoms and preferably being branched, and which includes one or more oxo groups, and B is hydro-gen, a pharmaceutically acceptable metal atom, an al-cohol bound as ester and having 1-5 carbon atoms and 1-3 hydroxy groups, or a glycerol group bound as ester, can be used as a nutrient substrate, an antimicrobial and antiviral agent, and/or as an agent for influencing the central nervous system. The invention also relates to compositions intended for the aforementioned usages and containing at least one compound A - B.
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- Semiconductor Effect on the Selective Photocatalytic Reaction of α-Hydroxycarboxylic Acids
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Photocatalytic and photoelectrochemical reactions of α-hydroxycarboxylic acids were compared for various types of semiconductor electrode (TiO2, CdS, SrTiO3, and ZnO) and suspension of particulate semiconductor (TiO2, CdS, MoS2, and ZnS).These reactions were found to depend strongly on the type of semiconductor studied.In the cases of Pt/CdS and ZnS photocatalysts, the hydroxy group of the acids was oxidized selectively into the corresponding keto acids, whereas in the cases of Pt/TiO2,decarboxylation took place in addition to dehydrogenation.The same dependence was observed in the photoelectrochemical reactions with semiconductor single crystal electrodes.For the TiO2 electrode, the reaction depends strongly on pH, whereas it does not for CdS.The results of pH effects, electrochemical reaction with metal electrodes, and Fenton reaction in a homogeneous solution suggest the importance of adsorption of the reactants on the semiconductor and metal surfaces for the selective reaction.
- Harada, H.,Ueda, T.,Sakata, T.
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p. 1542 - 1548
(2007/10/02)
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- Purification and Inhibition of Spinach &α,&β-Dihydroxyacid Dehydratase
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The α,β-dihydroxyacid dehydratase (E.C. 4.2.1.9) responsible for the production of α-oxoisovaleric acid in the valine biosynthetic pathway has been purified from spinach leaves.Its properities are similar to those given in a previous report using a less pure preparation.Its monomer mass is estimated to be 55 kDa.Evidence for an enol intermediate in the reaction mechanism has been obtained by a deuterium labeling study.Several inhibitors have been screened against the enzyme.Four of particular effectiveness are 4-fluoro-3,3-dihydroxyisovaleric acid, 1-hydroxy-1-isobutanesulfonic acid, N,N-dimethylglycine N-oxide, and 2-fluoro-3,3-dimethylacrylic acid.As an enol analogue, the latter compound gives further evidence for enol itermediate.
- Pirrung, Michael C.,Ha, Hyun-Joon,Holmes, Christopher P.
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p. 1543 - 1548
(2007/10/02)
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- An Evaluation of the Substrate Specificity, and of Its Modification by Site-Directed Mutagenesis, of the Cloned L-Lactate Dehydrogenase from Bacillus stearothermophilus
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The L-lactate dehydrogenase of Bacillus stearothermophilus (BSLDH) is a stable, thermophilic oxidoreductase.It has been selected as a model of enzymes with considerable future promise in assymetric synthesis in that it has been cloned to ensure a plentiful and inexpensive supply and because of the potential for tailoring its specificity to accept unnatural substrate structures via the site-directed mutagenesis techniques of moleculer biology.In this study, the specificity of BSLDH toward representative α-keto acids possessing straight- and branched-chain alkyl,cycloalkyl, or aromatic side chains has been evaluated.The results show that substrates that are sterically bulky in the region of the α-keto group to be reduced are poorly accepted by the enzyme.Graphics analyses indicated that the low activities of these hindered substrates might be partly due to a bad interaction of the active site residue Gln102 with large or branched substituents adjacent to the α-keto group.Accordingly, Gln102 has been replaced by the smaller Asn residue by site-directed mutagenesis in an attempt to expand the active site volume available to receive substrates larger than the natural pyruvate.However, the kinetic data show that bulky α-keto acids are only marginally better accommodated by the Gln102 -> Asn mutant than by the wild-type enzyme.
- Luyten, Marcel A.,Bur, Daniel,Wynn, Hla,Parris, Wendy,Glod, Marvin,et al.
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p. 6800 - 6804
(2007/10/02)
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- Synthesis and Stereochemistry of Indolactam-V, An Active Fragment of Teleocidins. Structural Requirements for Tumor-Promoting Activity.
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(-)-Indolactam-V, which is an active fragment of the potent tumor promoters teleocidins and has also been isolated as a Streptoverticillium metabolite, has been synthesized starting from 4-nitrogramine.The absolute stereochemistry of (-)-indolactam-V has been determined to be (9S, 12S), which suggests that teleocidins and related compounds are biosinthesyzed from L-amino acids.Three unnatural diastereoisomers were also synthesized.The NMR spectra of (-)- and (+/-)-indolactam-V and its derivatives showed that they exist in two conformational states in solution.The structures of the two conformers were deduced from the chemical shifts, coupling constants and nuclear Overhauser effects to be SOFA and TWIST from which are characterized by trans and cis amide bonds, respectively.The calculated ratio of the two conformers was consistent with the observed ratio.
- Endo, Yasuyuki,Shudo, Koichi,Itai, Akiko,Hasegawa, Masashi,Sakai, Shin-ichiro
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p. 5905 - 5924
(2007/10/02)
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- Process for preparing α-keto-carboxylic acids from acyl halides
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A process for the production of α-keto-carboxylic acids of the general formula: STR1 wherein R1 and R2 are the same or different and are hydrogen, hydrocarbyl radicals, substituted hydrocarbyl radicals or hydrocarbyloxy radicals by reacting an acyl halide of the formula: STR2 wherein R1 and R2 are as defined above and X represents halogen, in a liquid solvent medium, with an alkali metal tetracarbonyl cobaltate complex of the formula: wherein M is an alkali metal to form the corresponding acylcobaltcarbonyl complex of the formula: STR3 wherein R1 and R2 are as defined above, reacting the acylcobaltcarbonyl complex thus formed with carbon monoxide and an alkali metal hydroxide or an alkaline earth metal hydroxide at elevated temperature and elevated pressure in a liquid solvent medium to form the corresponding alkali metal salt or alkaline earth metal salt of the product α-keto-carboxylic acid and thereafter acidifying the salt of the α-keto-carboxylic acid to form the product α-keto-carboxylic acid.
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- Preparation of α-keto-carboxylic acids from acyl halides
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A process for the production of α-keto-carboxylic acids of the general formula: STR1 wherein R1 and R2 are the same or different and are hydrogen, hydrocarbyl radicals, substituted hydrocarbyl radicals or hydrocarbyloxy radicals by reacting an acyl halide of the formula: STR2 wherein R1 and R2 are as defined above and X represents halogen, in a liquid solvent medium, with an alkali metal tricarbonyl[triphenylphosphine]cobaltate complex of the formula: wherein M is an alkali metal to form the corresponding phenylacetyl tricarbonyl[triphenylphosphine]cobalt complex of the formula: STR3 wherein R1 and R2 are as defined above, reacting the acylcobaltcarbonyl complex thus formed with carbon monoxide and an alkali metal hydroxide or an alkaline earth metal hydroxide at elevated temperature and elevated pressure in a liquid solvent medium to form the corresponding alkali metal salt or alkaline earth metal salt of the product α-keto-carboxylic acid and thereafter acidifying the salt of the α-keto-carboxylic acid to form the product α-keto-carboxylic acid.
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- Process for preparing α-ketocarboxylic acids
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A novel process for the manufacture of α-ketocarboxylic acids which comprises the reaction of oximinohalide with cyanide ion to form oximinonitrile which is reacted with hydroxide ion to form oximinoacid and hydrolysis thereof to the α-ketoacid.
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- Process for the preparation of oximinonitriles
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A novel process for the manufacture of oximinonitriles which comprises the reaction of an oximinohalide with cyanide ion.
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