- An expedient synthesis of N-(1-(5-mercapto-4-((substituted benzylidene)amino)-4H-1,2,4-triazol-3-yl)-2-phenylethyl)benzamides as jack bean urease inhibitors and free radical scavengers: Kinetic mechanism and molecular docking studies
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In this study, some new azomethine-triazole hybrids 5a–5l derived from N-benzoyl-L-phenylalanine were synthesized and characterized. The synthesized compounds showed first-rate, urease inhibition, and compounds 5c and 5e were found to be most effective inhibitors with 0.0137?±?0.00082?μm and 0.0183?±?0.00068?μm, respectively (thiourea 15.151?±?1.27?μm). The kinetic mechanism of urease inhibition revealed the compounds 5c and 5e to be non-competitive inhibitors, whereas compounds 5d and 5j were found to be of mixed-type inhibitors. Docking studies also indicated better interaction patterns with urease enzyme. The results of enzyme inhibition, kinetic mechanism and molecular docking suggest that these compounds can serve as lead compounds in the design of more effective urease inhibitors.
- Saeed, Aamer,Larik, Fayaz Ali,Channar, Pervaiz Ali,Mehfooz, Haroon,Ashraf, Mohammad Haseeb,Abbas, Qamar,Hassan, Mubashir,Seo, Sung-Yum
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- N-BENZOYLPHENYLALANINE AND N-BENZOYLPHENYLALANINOL, AND THEIR BIOSYNTHESIS IN PENICILLIUM BREVICOMPACTUM
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N-Benzoylphenylalanine and N-benzoylphenylalaninol have been detected in cultures of Penicillium brevicompactum.Isotope from phenylalanine was incorporated effectively into the benzoyl group of both compounds.Key Word Index- Penicillium brevicompactum; fungus; biosynthesis; N-benzoylphenylalanine; N-benzoylphenylalninol.
- Doerfler, Dennis L.,Bird, Bruce A.,Campbell, Iain M.
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- Inhibition effects in the hydrolysis reactions of esters and peptides catalyzed by carboxypeptidase A: An example of cooperative binding effects with a monomeric enzyme
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N-benzoyl-L-phenylalanyl-L-phenylalanine is an excellent peptide substrate for carboxypeptidase A; at 30°C and pH 7.5, Km is 2.6 × 10-5 M while κcat is 177 s-1 κcat/Km = 6.8 × 106 M-1 s-1). Indole-3-acetic acid is a noncompetitive or mixed inhibitor towards the peptide and toward hippuryl-L-phenylalanine; plots of E/V vs [Inhibitor] are linear. N-Benzoyl-L-phenylalanine is a competitive inhibitor of peptide hydrolysis, and plots of E/V vs [Inhibitor] are again linear. One molecule of inhibitor binds per active site, and these inhibitors bind in different sites. At constant peptide substrate concentration and a series of constant concentrations of indole-3-acetic acid, plots of E/V vs the concentration of N-benzoyl-L-phenylalanine are linear and intersect behind the E/V axis and above the [Inhibitor] axis. This shows that both inhibitors can bind simultaneously and that binding of one facilitates the binding of the other (β = 0.18). Employing the ester substrate hippuryl-DL,βphenyllactate, the same type of behavior is observed in the reverse sense; N-benzoyl-L-phenylalanine is a linear noncompetitive inhibitor and indole-3-acetic acid is a linear competitive inhibitor. Again the two inhibitor plot is linear and intersects above the [Inhibitor] axis (β = 0.12). Previous X-ray crystallographic studies have indicated that indole-3-acetic acid binds in the hydrophobic pocket of the S1 site, while N-benzoyl-L-phenylalanine binds in the S1-S2 site. The product complex for hydrolysis of N-benzoyl-L-phenylalanyl-L-Phenylalanine (phenylalanine + N-benzoyl-L-phenylalanine) occupies both of these sites. However, the present work shows that the peptide substrate does not bind to the enzyme at pH 7.5 so as to be competitive with indole-3-acetic acid. The binding sites may be formed via conformational changes induced or stabilized by substrate and product binding.
- Rahmo, Abdulkader,Fife, Thomas H.
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- OCCURRENCE AND BIOSYNTHESIS OF ASPERPHENAMATE IN SOLID CULTURES OF PENICILLIUM BREVICOMPACTUM
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The ester of N-benzoylphenylalanine and N-benzoylphenylalaninol, asperphenamate, was isolated from solid cultures of Penicillium brevicompactum.Isotope from L-phenylalanine was well incorporated into both benzoyl groups and into the phenylalanine and phenylalaninol moieties.Isotope from benzoic acid was also well incorporated into asperphenamate.Key Word Index-Penicillium brevicompactum; Hyphomycetes; fungus; biosynthesis; asperphenamate; phenylalanine derivatives.
- Bird, Bruce A.,Campbell, Iain M.
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- Tuning lipase enantioselectivity in organic media using solid-state buffers
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The enantioselectivity exhibited by Candida antarctica lipase B (CALB) in predominantly organic media has been studied for different enzyme protonation states. Alcoholysis of (±)-2-phenyl-4-benzyloxazol-5(4H)-one (1) using butan-1-ol as the nucleophile in low-water organic solvents was used as a model reaction. Using either organo-soluble bases or the newly introduced solid-state buffers of known pKa, the protonation state of the lipase was altered. By choice of the appropriate solid-state buffer or organic base, the enantioselectivity could be selectively tuned. Both Et3N and the solid-state buffer pair CAPSO/CAPSO.Na were found to increase the enantioselectivity of the reaction catalyzed by CALB and that of another lipase (Mucor miehei). Significant differences to both the enantioselectivity and catalytic rate were observed, especially under hydrated conditions where byproduct acid was formed.
- Quiros,Parker,Turner
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- Electrophilic Sulfonium-Promoted Peptide and Protein Amidation in Aqueous Media
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A novel amidation strategy using electrophilic sulfonium, which is soluble and stable in aqueous conditions, was developed. The sulfoniums could activate thioacid and carboxyl acid to efficiently react with amines to afford amides. This method enables applications in amidation in both aqueous media and solid-phase peptide synthesis, peptide/protein modifications, and reactive lysines of a proteome at pH 10 with activity-based protein profiling. A peptide ligand-directed labeling of the USP7-UBL2 domain was also performed using this method.
- Wan, Chuan,Feng, Yuan,Hou, Zhanfeng,Lian, Chenshan,Zhang, Liang,An, Yuhao,Sun, Jinming,Yang, Dongyan,Jiang, Chenran,Yin, Feng,Wang, Rui,Li, Zigang
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supporting information
p. 581 - 586
(2022/01/20)
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- Hybrids of aurantiamide acetate and isopropylated genipin as potential anti-inflammatory agents: The design, synthesis, and biological evaluation
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A novel series of hybrids designed on the basis of aurantiamide acetate and isopropylated genipin were synthesized and biologically evaluated as anti-inflammatory agents. Among them, compound 7o exhibited the best inhibitory activity against TNF-α secretion (IC50?=?16.90?μM) and was selected for further in vitro and in vivo functional study. The results demonstrated that 7o was capable of suppressing the expression of LPS-induced iNOS and COX-2, as well as reducing the production of NO at the concentration of 5?μM, which may be resulted from its regulation of NF-κB signaling and MAPK signaling. Moreover, compound 7o exhibited favorable in vivo anti-inflammatory activity with an inhibition rate of 53.32% against xylene-induced ear swelling in mice at the dose of 5?mg/kg.
- Wang, Hongwei,Gao, Sufan,Li, Jiaming,Ma, Xiaodong,Liu, Wandong,Qian, Shihu
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p. 797 - 808
(2020/12/03)
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- Identification and validation of selective deubiquitinase inhibitors
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Deubiquitinating enzymes (DUBs) are a class of isopeptidases that regulate ubiquitin dynamics through catalytic cleavage of ubiquitin from protein substrates and ubiquitin precursors. Despite growing interest in DUB biological function and potential as therapeutic targets, few selective small-molecule inhibitors and no approved drugs currently exist. To identify chemical scaffolds targeting specific DUBs and establish a broader framework for future inhibitor development across the gene family, we performed high-throughput screening of a chemically diverse small-molecule library against eight different DUBs, spanning three well-characterized DUB families. Promising hit compounds were validated in a series of counter-screens and orthogonal assays, as well as further assessed for selectivity across expanded panels of DUBs. Through these efforts, we have identified multiple highly selective DUB inhibitors and developed a roadmap for rapidly identifying and validating selective inhibitors of related enzymes.
- Auld, Douglas,Buhrlage, Sara J.,Casalena, Dominick,Chan, Wai Cheung,Dhe-Paganon, Sirano,Hu, Bin,Liu, Xiaoxi,Magin, Robert S.,Marto, Jarrod A.,Roberts, Rebekka M.,Seo, Hyuk-Soo,Varca, Anthony C.,Zhu, He
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p. 1758 - 13,1771
(2021/12/20)
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- Nickel-Catalyzed Multicomponent Coupling: Synthesis of α-Chiral Ketones by Reductive Hydrocarbonylation of Alkenes
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A nickel-catalyzed, multicomponent regio- and enantioselective coupling via sequential hydroformylation and carbonylation from readily available starting materials has been developed. This modular multicomponent hydrofunctionalization strategy enables the straightforward reductive hydrocarbonylation of a broad range of unactivated alkenes to produce a wide variety of unsymmetrical dialkyl ketones bearing a functionalized α-stereocenter, including enantioenriched chiral α-aryl ketones and α-amino ketones. It uses chiral bisoxazoline as a ligand, silane as a reductant, chloroformate as a safe CO source, and a racemic secondary benzyl chloride or an N-hydroxyphthalimide (NHP) ester of a protected α-amino acid as the alkylation reagent. The benign nature of this process renders this method suitable for late-stage functionalization of complex molecules.
- Chen, Jian,Zhu, Shaolin
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supporting information
p. 14089 - 14096
(2021/09/13)
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- Rh(iii)-Catalyzed diastereoselective transfer hydrogenation: An efficient entry to key intermediates of HIV protease inhibitors
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A highly efficient diastereoselective transfer hydrogenation of α-aminoalkyl α′-chloromethyl ketones catalyzed by a tethered rhodium complex was developed and successfully utilized in the synthesis of the key intermediates of HIV protease inhibitors. With the current Rh(iii) catalyst system, a series of chiral 3-amino-1-chloro-2-hydroxy-4-phenylbutanes were produced in excellent yields and diastereoselectivities (up to 99% yield, up to 99?:?1 dr). Both diastereomers of the desired products could be efficiently accessed by using the two enantiomers of the Rh(iii) catalyst.
- Chen, Gen-Qiang,Lang, Qi-Wei,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie,Wang, Fangyuan,Wu, Ting,Yin, Congcong,Zhang, Xumu,Zheng, Long-Sheng
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supporting information
p. 3119 - 3122
(2020/03/23)
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- On the intrinsic reactivity of highly potent trypanocidal cruzain inhibitors
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The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies
- Batista, Pedro Henrique Jatai,Bonatto, Vinicius,Cedron, Rodrigo,Cianni, Lorenzo,De Vita, Daniela,Franco, Caio Haddad,Montanari, Carlos A.,Moraes, Carolina Borsoi,Silva, Daniel G.,Tezuka, Daiane Y.,De Albuquerque, Sérgio,Lameira, Jer?nimo,Leit?o, Andrei
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supporting information
p. 1275 - 1284
(2020/12/01)
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- Organocatalytic asymmetric [4+2] cyclization of 2-benzothiazolimines with azlactones: Access to chiral benzothiazolopyrimidine derivatives
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An organocatalytic asymmetric domino Mannich/cyclization reaction between 2-benzothiazolimines with azlactones has been successfully developed. With the bifunctional squaramide catalyst, this formal [4+2] cyclization occurs with good to high yields and excellent stereoselectivities (up to 99% ee, >20?:?1 dr), providing an efficient and mild access to chiral benzothiazolopyrimidines bearing adjacent tertiary and quaternary stereogenic centers.
- Ni, Qijian,Wang, Xuyang,Xu, Fangfang,Chen, Xiaoyun,Song, Xiaoxiao
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supporting information
p. 3155 - 3158
(2020/03/23)
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- Asymmetric trifluoromethylthiolation of azlactones under chiral phase transfer catalysis
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The first enantioselective method for the installation of the SCF3 group at the C-4 position of azlactones is described in the present communication under quinidinium phase transfer catalysis. The higher performance of substrates containing electron-rich 2-aryl groups at the azlactone was rationalized using DFT calculations.
- Alemán, José,Bernardi, Luca,Borello, Fabio,Cano, Rafael,Capaccio, Vito,Díaz-Tendero, Sergio,De Riccardis, Francesco,Della Sala, Giorgio,Rodríguez, Ricardo I.,Sicignano, Marina
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supporting information
p. 2914 - 2920
(2020/04/28)
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- A Facile Approach to the Synthesis of Benzothiazoles from N-Protected Amino Acids
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Abstract: –A simple trituration method for the synthesis of 2-substituted benzothiazoles derived from N-protected amino acids and 2-aminothiophenol using molecular iodine as a mild Lewis acid catalyst has been proposed. The reaction occurs in one step for 20–25 min in solve-free conditions and provides the target products in excellent yields.
- Arfan, M.,Fatima, T.,Mannan, A.,Tahira, A.
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p. 292 - 297
(2020/04/21)
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- Asymmetric Aza-Diels-Alder Reactions of in Situ Generated β,β-Disubstituted α,β-Unsaturated N-H Ketimines Catalyzed by Chiral Phosphoric Acids
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A novel asymmetric synthesis of dihydropyridinones with vicinal quaternary stereocenters has been realized by asymmetric aza-Diels-Alder reactions of 3-amido allylic alcohols with oxazolones enabled by chiral phosphoric acid catalysis. A series of aryl/alkyl- and alkyl/alkyl-disubstituted 3-amido allylic tertiary alcohols and 4-substituted oxazolones could be well tolerated in these reactions, producing dihydropyridinones with excellent diastereoselectivities and high enantioselectivities. Mechanistic study and control experiments were performed to shed light on the reaction mechanism, in which a configurationally defined β,β-disubstituted α,β-unsaturated N-H ketimine was proposed as the key intermediate.
- He, Shunlong,Gu, Huanchao,He, Yu-Peng,Yang, Xiaoyu
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supporting information
p. 5633 - 5639
(2020/07/14)
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- Multi-Institution Research and Education Collaboration Identifies New Antimicrobial Compounds
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New antibiotics are urgently needed to address increasing rates of multidrug resistant infections. Seventy-six diversely functionalized compounds, comprising five structural scaffolds, were synthesized and tested for their ability to inhibit microbial growth. Twenty-six compounds showed activity in the primary phenotypic screen at the Community for Open Antimicrobial Drug Discovery (CO-ADD). Follow-up testing of active molecules confirmed that two unnatural dipeptides inhibit the growth of Cryptococcus neoformans with a minimum inhibitory concentration (MIC) ≤ 8 μg/mL. Syntheses were carried out by undergraduate students at five schools implementing Distributed Drug Discovery (D3) programs. This report showcases that a collaborative research and educational process is a powerful approach to discover new molecules inhibiting microbial growth. Educational gains for students engaged in this project are highlighted in parallel to the research advances. Aspects of D3 that contribute to its success, including an emphasis on reproducibility of procedures, are discussed to underscore the power of this approach to solve important research problems and to inform other coupled chemical biology research and teaching endeavors.
- Fuller, Amelia A.,Dounay, Amy B.,Schirch, Douglas,Rivera, Daniel G.,Hansford, Karl A.,Elliott, Alysha G.,Zuegg, Johannes,Cooper, Matthew A,Blaskovich, Mark A. T.,Hitchens, Jacob R.,Burris-Hiday, Sarah,Tenorio, Kristiana,Mendez, Yanira,Samaritoni, J. Geno,O'Donnell, Martin J.,Scott, William L.
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p. 3187 - 3196
(2020/12/21)
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- Reactivity of Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide towards some carbon electrophiles. A comparative study
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Z- and E-isomers of 2-benzamido-3-phenylacrylohydrazide 2a, 2b have different relative reactivities towards some carbon electrophiles had been discussed.The Z-isomer underwent cyclization to give imidazole derivative 3 and triazine derivative 4, whereas the latter E-isomer does not undergo such cyclization. The reaction of 2a and/or 2b with 1,2-dibenzylidene hydrazine at different reaction conditions afforded the Schiff bases 6, 8 and the triazolidine derivative 9. Reactions of 2a, 2b with formic acid and phthalic anhydride gave the different cyclization products 10–14, respectively. The structures of all the new synthesized compounds were established from their IR, 1H-NMR and mass spectra as well as elemental analyses.
- Abou-Elregal, Mohsen K.,Youssef, Ahmed S. A.,Hemdan, Magdy M.,Samir, Sandy S.
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p. 2369 - 2378
(2019/07/03)
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- GRANZYME B DIRECTED IMAGING AND THERAPY
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Provided herein are heterocyclic compounds useful for imaging Granzyme B. Methods of imaging Granzyme B, combination therapies, and kits comprising the Granzyme B imaging agents are also provided.
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Page/Page column 82; 99
(2019/09/04)
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- Palladium-catalyzed asymmetric decarboxylative allylation of azlactone enol carbonates: Fast access to enantioenriched α-allyl quaternary amino acids
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We report a fast protocol for the synthesis of enantioenriched quaternary 4-allyl oxazol-5-ones. The key step is a Pd-catalyzed enantioselective Tsuji allylation of azlactone allyl enol carbonates, which can be easily prepared starting from racemic α-amino acids. The use of (R,R)-DACH-phenyl Trost chiral ligand allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. Scaling up the allylation protocol to gram quantities did not affect the yields end ee values. The produced 4-allyl azlactones can be converted into the corresponding quaternary amino acids or submitted to further synthetic elaborations exploiting the allyl moiety as a handle for the attachment of alkyl and aryl groups. After hydrolysis of the azlactone ring, the zwitterionic amino acids can be attained in enantiopure or nearly optically pure form through only one recrystallization step.
- Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,De Lorenzi, Ersilia,Colombo, Lino
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p. 732 - 741
(2019/01/09)
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- Enantioselective synthesis of pyrano[2,3-: C] pyrrole via an organocatalytic [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones
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An enantioselective [4 + 2] cyclization reaction of dioxopyrrolidines and azlactones has been successfully developed through a squaramide catalysis strategy. This protocol provides an efficient and mild access to obtain pyrano[2,3-c]pyrrole scaffolds containing contiguous quaternary and tertiary stereogenic centers in excellent yields (up to 99%) with high levels of diastereo- and enantioselectivities (up to 99% ee). Two possible pathways were proposed to explain the observed stereoselectivity.
- Wang, Yichen,Chen, Yuzhen,Li, Xiaoping,Mao, Yukang,Chen, Weiwen,Zhan, Ruoting,Huang, Huicai
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supporting information
p. 3945 - 3950
(2019/04/30)
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- Asymmetric construction of dihydrobenzofuran-2,5-dione derivatives via desymmetrization of p-quinols with azlactones
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The desymmetrization of p-quinols through a chiral bisguanidinium hemisalt catalyzed enantioselective Michael addition/lactonization cascade reaction with azlactones was reported. 3-Amino-benzofuran-2,5-diones containing a chiral amino acid residue were achieved with up to 99% ee and >19?:?1 dr. An exploration of the structure of the catalyst bisguanidinium was undertaken, revealing a bifunctional catalytic model.
- Xie, Lihua,Dong, Shunxi,Zhang, Qian,Feng, Xiaoming,Liu, Xiaohua
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supporting information
p. 87 - 90
(2019/01/03)
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- Novel Triazole Compounds and Use thereof
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The novel triazole compound of the present invention is suitable for use as a pharmaceutical composition and an antioxidant composition for the treatment or prevention of diseases selected from the group consisting of gastrointestinal diseases, duodenal diseases, liver diseases, and renal diseases. (by machine translation)
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Paragraph 0075; 0076
(2019/12/13)
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- A Hydroperoxide-Mediated Decarboxylation of α-Ketoacids Enables the Chemoselective Acylation of Amines
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Strategies for the formation of amide bonds, that is, one of the most basic and important transformations in organic synthesis, have so far focused predominantly on dehydration reactions. Herein, we report and demonstrate the practical utility of a novel decarboxylative amidation of α-ketoacids by using inexpensive tert-butyl hydroperoxide (TBHP), which is characterized by high yields, a broad substrate scope, mild reaction conditions, and a unique chemoselectivity. These features enable the synthesis of peptides from amino acid derived α-ketoacids under preservation of the stereochemical information.
- Nanjo, Takeshi,Kato, Natsuki,Zhang, Xuan,Takemoto, Yoshiji
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supporting information
p. 15504 - 15507
(2019/11/14)
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- Design, synthesis and evaluation of novel phenyl propionamide derivatives as non-nucleoside hepatitis B virus inhibitors
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As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC50 values on HBV DNA replication of 0.46 and 0.14 μM, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153.14, suggesting that 8d and 9b exhibited favorable safety profiles. Interestingly, 8d and 9b possessed significantly antiviral activities against lamivudine and entecavir resistant HBV mutants with IC50 values of 0.77 and 0.32 μM. Notably, preliminary anti-HBV action mechanism studies showed that 8d could inhibit intracellular HBV pgRNA and RT activity of the HBV polymerase. Molecular docking studies suggested that compound 8d could fit into the dimer-dimer interface of HBV core protein by hydrophobic interaction. In addition, in silico prediction of physicochemical properties showed that 8d conformed well to the Lipinski's rule of five, suggesting its potential for use as a drug like molecule. Taken together, 8d possessed significantly anti-HBV activity, low toxicity, diverse anti-HBV mechanism and favorable physicochemical properties, and warranted further investigation as a promising non-nucleoside anti-HBV candidate.
- Qiu, Jingying,Gong, Qineng,Gao, Jian,Chen, Wang,Zhang, Yinpeng,Gu, Xiaoke,Tang, Daoquan
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p. 424 - 434
(2018/01/01)
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- Design, synthesis, and molecular docking studies of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives as xanthine oxidase inhibitors
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A series of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives (1a–j) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D-phenylalanine derivatives (1d and 1i) and the L/D-tryptophan derivatives (1e and 1j) were effective with micromolar level potency. In particular, the L-phenylalanine derivative 1d (IC50?=?3.0?μm) and the D-phenylalanine derivative 1i (IC50?=?2.9?μm) presented the highest potency and were both more potent than the positive control allopurinol (IC50?=?8.1?μm). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D-amino acid derivative presented equal or greater potency compared to its L-enantiomer; and the 9,10-anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.
- Zhang, Ting-Jian,Li, Song-Ye,Yuan, Wei-Yan,Zhang, Yi,Meng, Fan-Hao
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p. 893 - 901
(2018/03/21)
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- Identification of 1,5,7-Triazabicyclododecene and Polystyrene-Supported Superbases as Efficient Hydroxylaminolysis Agents of Sterically Hindered and Epimerizable Esters
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In modern pharmaceutical research, the need for reliable protocols for the preparation of chemical libraries in a controlled manner is quintessential to driving the Design-Make-Test cycle in drug discovery programs. In this letter, we communicate the iden
- Pierre, Romain,Gaigne, Frédéric,El-Bazbouz, Ghizlane,Mouis, Grégoire,Ouvry, Gilles,Tomas, Loic,Harris, Craig S.
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p. 1102 - 1106
(2018/04/24)
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- STRUCTURE AND SYNTHESIS OF HIGHLY FLUORINATED AMINO ACID DERIVATIVES
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Methods of synthesizing polyfluorinated amino acid derivatives are disclosed, along with polyfluorinated amino acid derivatives produced from said methods, as well as compositions containing same. The synthesis methods utilize an oxazolone and a perfluoroarene to produce the polyfluorinated amino acid derivatives.
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Paragraph 0164; 0165; 0166; 0167
(2018/09/19)
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- Dynamic Kinetic Resolution of Azlactones by a Chiral N, N-Dimethyl-4-aminopyridine Derivative Containing a 1,1′-Binaphthyl Unit: Importance of Amide Groups
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A dynamic kinetic resolution (DKR) of azlactones in the presence of benzoic acid and a binaphthyl-based N,N-4-dimethylaminopyridine (DMAP) derivative 1i having two amide groups at the 3,3′-positions of a binaphthyl unit is developed. The reaction proceeded smoothly with a wide range of azlactones to provide α-amino acid derivatives with good to high enantiomeric ratios (er's). A multigram-scale reaction (2.5 g) for the DKR of azlactone 2d was also demonstrated, and the resulting product was converted to unnatural α-amino acid 6d′.
- Mandai, Hiroki,Hongo, Kohei,Fujiwara, Takuma,Fujii, Kazuki,Mitsudo, Koichi,Suga, Seiji
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supporting information
p. 4811 - 4814
(2018/08/24)
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- USP30 INHIBITORS
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The application relates to phenyl- or naphthylsulfonamide derivatives of the structural formula (I). The compounds are described as inhibitors of USP30 (ubiquitin specific peptidase 30) useful for the treatment of conditions involving mitochondrial defects including neurodegenerative diseases such as Alzheimer's and Parkinson's or a neoplastic disease such as leukemia.
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Page/Page column 20; 25; 27
(2018/12/13)
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- Tertiary-butoxycarbonyl (Boc) – A strategic group for N-protection/deprotection in the synthesis of various natural/unnatural N-unprotected aminoacid cyanomethyl esters
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A number of cyanomethyl esters of natural/unnatural aminoacids with un-protected amino functionality were synthesized because of their synthetic and medicinal importance. Critical N-Boc deprotection methods in the presence of labile (hydrolytic sensitivity) cyanomethyl functionality were screened thoroughly and it was found that readily available 4M HCl in 1,4-dioxane solution (2–4 equiv); acetonitrile, 0 °C, 2–4 h was a suitable condition. This condition was generalized and successfully applied to a variety of alkyl, alkynyl, aryl, heteroaryl, benzyl, azido, spiro amino acid cyanomethylesters irrespective of the nature of the amine (primary or secondary) and the distance between the amine and ester group to achieve final deprotected amino esters with high yield, and purity compared to other commonly known N-protecting groups (Cbz, Fmoc, Ac, Bn, Bz etc.). It was also demonstrated that N-Boc protected aminoacid cyanomethylesters are stable enough to carry out further functionalization compared to N-unprotected counterparts.
- Karmakar, Ananta,Basha, Mushkin,Venkatesh Babu,Botlagunta, Murali,Malik, Noormohamed Abdul,Rampulla, Richard,Mathur, Arvind,Gupta, Arun Kumar
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supporting information
p. 4267 - 4271
(2018/11/03)
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- Latent Bronsted Base Solvent-Assisted Amide Formation from Amines and Acid Chlorides
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Weakly basic amines, including even neutral amines such as nitroaniline and aminocarboxylic acids, react with acid chlorides very efficiently in N, N -dimethylacetamide (DMAC), without addition of a base, to give the corresponding amides in high yields. The role of DMAC and related solvents as latent Bronsted bases was studied in these amidation reactions. Less basic amines, such as aromatic amines, reacted with benzoyl chloride faster than more basic aliphatic amines.
- Otsuka, Rikuto,Maruhashi, Kazuo,Ohwada, Tomohiko
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supporting information
p. 2041 - 2057
(2018/05/04)
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- Formation of Non-Natural α,α-Disubstituted Amino Esters via Catalytic Michael Addition
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The enolate monoanion of amino esters is explored, and the first catalytic Michael addition of α-amino esters is demonstrated. These studies indicate that the acidity of the αC-H is the primary factor determining reactivity. Thus, polyfluorophenylglycine amino esters yield novel α-amino esters in the presence of a catalytic amount of a guanidine-derived base and Michael acceptors. Reactivity requires an acidic N-H, which is accomplished using common protecting groups such as N-Bz, N-Boc, and N-Cbz. Calculations and labeling experiments provide insight into the governing principles in which a key C-to-N proton transfer occurs, resulting in an expansion of the scope to include a number of natural amino esters. The study culminates with a late-stage functionalization of peptidic γ-secretase inhibitor, DAPT.
- Teegardin, Kip A.,Gotcher, Lacey,Weaver, Jimmie D.
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supporting information
p. 7239 - 7244
(2018/11/25)
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- Dynamic Kinetic Resolution of N-Protected Amino Acid Esters via Phase-Transfer Catalytic Base Hydrolysis
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Asymmetric base hydrolysis of α-chiral esters with synthetic small-molecule catalysts is described. Quaternary ammonium salts derived from quinine were used as chiral phase-transfer catalysts to promote the base hydrolysis of N-protected amino acid hexafluoroisopropyl esters in a CHCl3/NaOH (aq) via dynamic kinetic resolution, providing the corresponding products in moderate to good yields (up to 99%) with up to 96:4 er. Experimental and computational mechanistic studies using DFT calculation and pseudotransition state (pseudo-TS) conformational search afforded a TS model accounting for the origin of the stereoselectivity. The model suggested π-stacking and H-bonding interactions play essential roles in stabilizing the TS structures.
- Yamamoto, Eiji,Wakafuji, Kodai,Furutachi, Yuho,Kobayashi, Kaoru,Kamachi, Takashi,Tokunaga, Makoto
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p. 5708 - 5713
(2018/05/30)
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- Asperphenamate biosynthesis reveals a novel two-module NRPS system to synthesize amino acid esters in fungi
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Amino acid esters are a group of structurally diverse natural products with distinct activities. Some are synthesized through an inter-molecular esterification step catalysed by nonribosomal peptide synthetase (NRPS). In bacteria, the formation of the intra-molecular ester bond is usually catalysed by a thioesterase domain of NRPS. However, the mechanism by which fungal NRPSs perform this process remains unclear. Herein, by targeted gene disruption in Penicillium brevicompactum and heterologous expression in Aspergillus nidulans, we show that two NRPSs, ApmA and ApmB, are sufficient for the synthesis of an amino acid ester, asperphenamate. Using the heterologous expression system, we identified that ApmA, with a reductase domain, rarely generates dipeptidyl alcohol. In contrast, ApmB was determined to not only catalyse inter-molecular ester bond formation but also accept the linear dipeptidyl precursor into the NRPS chain. The mechanism described here provides an approach for the synthesis of new small molecules with NRPS as the catalyst. Our study reveals for the first time a two-module NRPS system for the formation of amino acid esters in nature.
- Li, Wei,Fan, Aili,Wang, Long,Zhang, Peng,Liu, Zhiguo,An, Zhiqiang,Yin, Wen-Bing
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p. 2589 - 2594
(2018/03/08)
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- Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid
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A novel method for the synthesis of trisubstituted oxazoles via a one-pot oxazole synthesis/Suzuki–Miyaura coupling sequence has been developed. One-pot formation of 5-(triazinyloxy)oxazoles using carboxylic acids, amino acids and a dehydrative condensing reagent, DMT-MM, followed by Ni-catalyzed Suzuki–Miyaura coupling with boronic acids provided the corresponding 2,4,5-trisubstituted oxazoles in good yields.
- Yamada, Kohei,Kamimura, Naoto,Kunishima, Munetaka
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p. 1478 - 1485
(2017/08/02)
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- Alpha-amino acrylate microbicide and preparation method and application thereof
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The invention provides an alpha-amino acrylate microbicide and a preparation method and application thereof. The alpha-amino acrylate microbicide has a specific chemical structure formula shown as a formula I, and the formula I is shown in the description. The alpha-amino acrylate microbicide has the advantages that by utilizing the design principle of pesticide molecules, a medical leading compound with anti-coronavirus activity is performed with structure modification of agricultural plant virus-resisting activity, a series of alpha-amino acrylate derivatives is designed and synthesized, and particularly, the alpha-amino acrylate derivative containing piperidine ring is synthesized; the known compound is used as a positive reference compound to systematically screen the biology activity; a plurality of high-efficiency anti-virus leading molecules are provided for the developing of new pesticides, and the positive meaning is realized for the reduction application of the pesticide and the protection of environment ecology.
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- Novel L-arginine derivatives as aminopeptidase N inhibitors: design, chemistry, and pharmacological evaluation
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Considering the important roles played in tumor, aminopeptidase N has been an appealing target for anti-tumor drug development. Here, a serial of novel aminopeptidase N inhibitors with L-arginine scaffold were designed, synthesized and evaluated for aminopeptidase N inhibitory activities. The preliminary anti-enzyme activity assay demonstrated that compounds 5e, 5h, 11e, 11g, and 11h showed comparable activities with the positive control bestatin, an approved aminopeptidase N inhibitor. In vitro anti-proliferation assay, compound 5f showed excellent activities against four kinds of tumor cells which overexpress aminopeptidase N. In vivo anti-metastasis assay, compounds 5f and 11g exhibited better activities than bestatin. So 5f and 11g should be lead compounds as novel aminopeptidase N inhibitors for further development.
- Mou, Jiajia,Luan, Yepeng,Chen, Danghui,Wang, Qiang
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p. 3015 - 3025
(2017/10/06)
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- MgI2-chemoselective cleavage for removal of amino acid protecting groups: A fresh vision for peptide synthesis
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In the field of peptide synthesis, the key to a successful access to synthetic targets lies on a pertinent combination of protecting groups. Their choice is directed by their selective removal conditions. We present here the behavior of some of the most used protecting groups in peptide chemistry under experimental cleavage conditions, combining MgI2 with MW irradiation, using 2-Me-THF as a green solvent. In these experimental conditions, the benzyloxycarbonyl protecting group as well as the Merrifield resin can be re-considered in peptide chemistry.
- Berthet, Mathéo,Martinez, Jean,Parrot, Isabelle
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- Polyfluoroarylation of oxazolones: Access to non-natural fluorinated amino acids
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Herein, conditions are provided for the formation and use of the oxazolone enolate for the nucleophilic substitution of highly fluorinated (hetero)arenes, which after unmasking yield highly fluorinated non-natural amino acids and derivatives. In addition, the properties and chemical behavior of this new class of amino acids are explored. The utility is demonstrated in the one pot synthesis of medicinally relevant 2-aminohydantoins.
- Teegardin, Kip A.,Weaver, Jimmie D.
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supporting information
p. 4771 - 4774
(2017/07/06)
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- Bifunctional squaramide-catalyzed synthesis of chiral dihydrocoumarins via ortho-quinone methides generated from 2-(1-tosylalkyl)phenols
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A bifunctional squaramide-catalyzed reaction of azlactones with o-quinone methides in situ generated from 2-(1-tosylalkyl)-phenols has been successfully developed under basic conditions, providing an efficient and mild access to chiral dihydrocoumarins bearing adjacent tertiary and quaternary stereogenic centers in high yields with excellent diastereo- and enantioselectivities.
- Zhou, Ji,Wang, Mao-Lin,Gao, Xiang,Jiang, Guo-Fang,Zhou, Yong-Gui
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supporting information
p. 3531 - 3534
(2017/03/30)
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- Palladium-Catalyzed Aminocarbonylation in Solid-Phase Peptide Synthesis: A Method for Capping, Cyclization, and Isotope Labeling
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A new synthetic approach for introducing N-capping groups onto peptides attached to a solid support, combining aminocarbonylation under mild conditions using a palladacycle precatalyst and solid-phase peptide synthesis, is reported. The use of a silacarboxylic acid as an in situ CO-releasing molecule allowed the reaction to be performed in a single vial. The method also enables versatile substitution of side chains, side-chain-to-side-chain cyclizations, and selective [13C] acyl labeling of modified peptides.
- Skogh, Anna,Friis, Stig D.,Skrydstrup, Troels,Sandstr?m, Anja
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supporting information
p. 2873 - 2876
(2017/06/07)
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- Design, synthesis and docking studies of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα- and αβ-amino acids
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A series of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα- and αβ-amino acids were designed and synthesized. Their structures were elucidated by 1H NMR, 13C NMR, LC-MS and HRMS. These compounds were evaluated for their β5 subunit inhibitory activities of human proteasome. The results showed that dipeptidyl boronic acid inhibitors composed of αα-amino acids were as active as bortezomib. Interestingly, the activities of those derived from αβ-amino acids lost completely. Of all the inhibitors, compound 22 (IC50 = 4.82 nM) was the most potent for the inhibition of proteasome activity. Compound 22 was also the most active against three MM cell lines with IC50 values less than 5 nM in inhibiting cell growth assays. Molecular docking studies displayed that 22 fitted very well in the β5 subunit active pocket of proteasome.
- Shi, Jingmiao,Lei, Meng,Wu, Wenkui,Feng, Huayun,Wang, Jia,Chen, Shanshan,Zhu, Yongqiang,Hu, Shihe,Liu, Zhaogang,Jiang, Cheng
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p. 1958 - 1962
(2016/04/05)
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- Enantiodivergent asymmetric catalysis with the tropos BIPHEP ligand and a proline derivative as chiral selector
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A catalytic system based on the tropos ligand BIPHEP and (S)-proline methyl ester as chiral selector was studied for Rh-catalysed asymmetric catalysis. By careful control of the catalyst preformation conditions, the enantioselectivity could be completely reversed in asymmetric hydrogenation of prochiral olefins maintaining the same absolute level in favorable cases. The enantiodivergent asymmetric catalysis could be rationalised by the interplay of the dynamic chirality (tropos) of the phosphine ligand and the coordination of the proline selector. Treating a suitable Rh-BIPHEP precursor with the (Sc)-proline-based ionic liquid led to an equimolar mixture of (RaSc)- and (SaSc)-diastereomers that is kinetically stable at 0 °C. At higher temperature, an irreversible diastereomerisation process was observed resulting in the diastereomerically pure (RaSc)-complex [Rh{(Ra)-BIPHEP}{(Sc)-ProlOMe}]. Whereas the use of the pure (RaSc)-complex led to 51% ee (R) in the hydrogenation of methyl 2-acetamidoacrylate, the S-product was formed with almost identical enantioselectivity when the (RaSc)/(SaSc)-mixture was applied under identical conditions. This inversion was associated with the relative stability of the diastereomers in the equilibria forming the catalytically active substrate complex. The possibility to use this different reactivity to control the direction of enantioselectivity was demonstrated for the hydrogenation of different substrates whereby ee's of up to 80% could be achieved. Moreover, the (RaSc)-complex led to high enantioselectivities of up 86% ee in the asymmetric hydroboration of styrene, approaching the performance of the atropos BINAP ligand for this reaction.
- Oczipka,Müller,Leitner,Franciò
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p. 678 - 683
(2015/12/30)
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- Efficient Synthesis of Glycosylated Matijin-Su Derivatives via Ultrasonic Irradiation
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Matijin-Su (1) is a phenylalanine dipeptide compound with anti-hepatitis B virus (HBV) activity. Previous reports suggest that the synthesis of glycosylated Matijin-Su derivatives needs at least 10 steps. To simplify the synthetic procedure, we have developed a shorter and more efficient method for the preparation via ultrasound irradiation. Two galactopyranosylated (2) and two glucopyranosylated (3) derivatives were synthesized in 6 or 7 steps. The overall yields for the total synthesis of galactopyranosylated derivatives were markedly increased to 39% (2a) or 22% (2b). And the yields for glucopyranosylated derivatives also reached 29% (3a) or 16% (3b).
- Liang, Guangping,Hu, Zhanxing,Yuan, Jie,Liang, Guangyi,Xu, Bixue
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p. 1353 - 1359
(2016/12/27)
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- Iron/caffeine as a catalytic system for microwave-promoted benzamide formation
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The amide bond is an essential unit in many drugs and polymers. The catalyzed oxidation of alcohols and amines is an effective method to form amides with limited undesired waste. Herein, we demonstrate the beneficial effect of microwave activation for this reaction. The benzamides were directly formed from alcohols and amine hydrochloride salts in short reaction times with yields up to 84% and TOFs (turnover frequencies) up to 33.6 h-1. Among the examined transition metals, only nontoxic and inexpensive FeCl2?·4H2O together with caffeine as a stabilizing ligand provided a uniquely efficient catalytic system for the transformation. Natural sources of caffeine were also evaluated under the amidation conditions.
- Bantreil, Xavier,Navals, Pauline,Martinez, Jean,Lamaty, Fr??d??ric
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p. 417 - 422
(2015/03/03)
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- The Role of the Amino Protecting Group during Parahydrogenation of Protected Dehydroamino Acids
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A series of dehydroamino acids endowed with different protective groups at the amino and carboxylate moieties and with different substituents at the double bond have been reacted with parahydrogen. The observed ParaHydrogen Induced Polarization (PHIP) effects in the 1H NMR spectra are strongly dependent on the amino protecting group. DFT calculations allowed us to establish a relationship between the structures of the reaction intermediates (whose energies depend on the amido substitution) and the observed PHIP patterns.
- Cerutti, Erika,Viale, Alessandra,Nervi, Carlo,Gobetto, Roberto,Aime, Silvio
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p. 11271 - 11279
(2015/12/01)
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- Isotope-labeled differential profiling of metabolites using N-benzoyloxysuccinimide derivatization coupled to liquid chromatography/high-resolution tandem mass spectrometry
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Rationale An isotopic labeling strategy based on derivatizing amine-containing metabolites has been developed using light (12C6) and heavy (13C6) N-benzoyloxysuccinimide reagents for semi-targeted metabolomic applications. Methods Differentially labeled samples were combined and analyzed simultaneously by liquid chromatography/high-resolution tandem mass spectrometry (LC/HR-MS/MS) to compare relative amounts of amine-containing metabolites. The selectivity of the reaction was determined with model metabolites and was shown to also be applicable to thiol and phenol moieties. The potential for relative quantitation was evaluated in cell extracts and the method was then applied to quantify metabolic perturbations occurring in human cultured cells under normal vs. oxidative stress conditions. Results A total of 279 derivatized features were detected in HL60 cell extracts, 77 of which yielded significant concentration changes upon oxidative stress treatment. Based on accurate mass measurements and MS/MS spectral matching with reference standard solutions, 10 metabolites were clearly identified. Derivatized compounds were found to have diagnostic fragment ions from the reagent itself, as well as structurally informative ions useful for metabolite identification. Conclusions This simple derivatization reaction can be applied to the relative quantitation of amine-, thiol- and phenol-containing compounds, with improved sensitivity and chromatographic peak shapes due to the increased hydrophobicity of polar metabolites not readily amenable to reversed-phase LC/MS analysis.
- Wagner, Michel,Ohlund, Leanne B.,Shiao, Tze Chieh,Vézina, Amélie,Annabi, Borhane,Roy, René,Sleno, Lekha
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p. 1632 - 1640
(2015/11/16)
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- Synthesis, Characterization, and Cytotoxicity of Palladium(II) Complexes with Diimine/Diamine and N-Carbonyl-L-Phenylalanine Dianion
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Six palladium(II) complexes, [Pd(bipy)(Bzphe-N,O)] (I-a), [Pd(bipy)(p-Mbzphe-N,O)]·2H2O (I-b), [Pd(bipy)(p-Nbzphe-N,O)]·2H2O (I-c), [Pd(phen)(Bmined by X-ray diffraction. The cytotoxicity test indicates that the complexes exert cytot
- Wang, Li-Wei,Liu, Si-Yuan,Wang, Jin-Jie,Peng, Wen,Li, Sheng-Hui,Zhou, Guo-Qiang,Qin, Xin-Ying,Wang, Shu-Xiang,Zhang, Jin-Chao
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p. 1049 - 1056
(2015/03/18)
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- Iron-catalyzed benzamide formation. Application to the synthesis of moclobemide
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A convenient and user-friendly method to yield benzamides from primary and secondary amines and various benzylic alcohols in the presence of a cheap iron salt (FeCl2·4H2O) and tert-butylhydroperoxide (70% in water) as a stoichiometric oxidant is described. Control experiments indicated that this reaction might involve radical species. This method proved to be general, generating a family of 30 benzamides and was applied to the preparative synthesis of anti-anxiety drug moclobemide.
- Bantreil, Xavier,Kanfar, Nasreddine,Gehin, Nicolas,Golliard, Ethan,Ohlmann, Pauline,Martinez, Jean,Lamaty, Frédéric
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p. 5093 - 5099
(2014/07/08)
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- Organocatalytic asymmetric biomimetic transamination of α-keto acetals to chiral α-amino acetals
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This paper describes a chiral base-catalyzed asymmetric biomimetic transamination of α-keto acetals. A wide variety of α-amino acetals containing various functional groups can be synthesized in 50-85% yield and 82-86% ee.
- Pan, Hongjie,Xie, Ying,Liu, Mao,Shi, Yian
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p. 2389 - 2392
(2014/01/06)
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- Enantioselective construction of tetrasubstituted stereogenic carbons through bronsted base catalyzed michael reactions: α′-hydroxy enones as key enoate equivalent
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Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Bronsted base (BB) catalysis and the use of α′-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α′-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α′-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
- Badiola, Eider,Fiser, Bla,Gmez-Bengoa, Enrique,Mielgo, Antonia,Olaizola, Iurre,Urruzuno, Iaki,Garca, Jess M.,Odriozola, Jos M.,Razkin, Jess,Oiarbide, Mikel,Palomo, Claudio
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supporting information
p. 17869 - 17881
(2015/02/19)
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- Peptide-catalyzed conversion of racemic oxazol-5(4 H)-ones into enantiomerically enriched α-amino acid derivatives
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We report the development and optimization of a tetrapeptide that catalyzes the methanolytic dynamic kinetic resolution of oxazol-5(4H)-ones (azlactones) with high levels of enantioinduction. Oxazolones possessing benzylic-type substituents were found to perform better than others, providing methyl ester products in 88:12 to 98:2 er. The mechanism of this peptide-catalyzed process was investigated through truncation studies and competition experiments. High-field NOESY analysis was performed to elucidate the solution-phase structure of the peptide, and we present a plausible model for catalysis.
- Metrano, Anthony J.,Miller, Scott J.
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p. 1542 - 1554
(2014/03/21)
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- Bronsted acid accelerated Pd-catalyzed direct asymmetric allylic alkylation of azlactones with simple allylic alcohols: A practical access to quaternary allylic amino acid derivatives
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A Bronsted acid accelerated Pd-catalyzed asymmetric allylic alkylation of azlactones with simple allylic alcohols under mild reaction conditions has been realized, which provides a direct and readily scalable approach for the synthesis of all-carbon quaternary allylic amino acid derivatives in excellent yields and good enantioselectivities. (Chemical Equation Presented).
- Zhou, Hui,Yang, Huameng,Liu, Muwen,Xia, Chungu,Jiang, Gaoxi
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supporting information
p. 5350 - 5353
(2015/01/09)
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- Organocatalyzed asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones: Synthesis of α,α-disubstituted α-amino acid derivatives
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The first asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones catalyzed by cinchona alkaloid derived bifunctional thiourea catalysts was developed. A series of α,α-disubstituted α-amino acid derivatives bearing a quaternary stereocenter at the α-position were obtained in high yields with excellent diastereo- and enantioselectivities (up to -20:1 dr and 99% ee). In addition, the trichloromethyl moiety in these adducts was identified as a good leaving group.
- Zhang, Jinlong,Liu, Xihong,Wu, Chongyang,Zhang, Panpan,Chen, Jianbo,Wang, Rui
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supporting information
p. 7104 - 7108
(2015/01/16)
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