- A short, efficient route of 1-hydroxylated vitamin D ring A fragments
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The bis-exocyclic conjugated diene system of vitamin D ring A synthons is efficiently constructed by means of a palladium-catalyzed intramolecular cyclization of the (Z)-iodoalkene resulting from the stereoselective hydrometallation-iodinolysis of proparg
- Mascarenas,Garcia,Castedo,Mourino
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Read Online
- Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles
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Despite many years of research and a few success stories with gene therapeutics, efficient and safe DNA delivery remains a major bottleneck for the clinical translation of gene-based therapies. Gene transfection with calcium phosphate (CaP) nanoparticles brings the advantages of low toxicity, high DNA entrapment efficiency and good endosomal escape properties. The macroscale aggregation of CaP nanoparticles can be easily prevented through surface coating with bisphosphonate conjugates. Bisphosphonates, such as alendronate, recently showed promising anticancer effects. However, their poor cellular permeability and preferential bone accumulation hamper their full application in chemotherapy. Here, we investigated the dual delivery of plasmid DNA and alendronate using CaP nanoparticles, with the goal to facilitate cellular internalization of both compounds and potentially achieve a combined pharmacological effect on the same or different cell lines. A pH-sensitive poly(ethylene glycol)-alendronate conjugate was synthetized and used to formulate stable plasmid DNA-loaded CaP nanoparticles. These particles displayed good transfection efficiency in cancer cells and a strong cytotoxic effect on macrophages. The in vivo transfection efficiency, however, remained low, calling for an improvement of the system, possibly with respect to the extent of particle uptake and their physical stability.
- Bisso, Sofia,Mura, Simona,Castagner, Bastien,Couvreur, Patrick,Leroux, Jean-Christophe
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- Nickel-catalyzed intramolecular [3 + 2 + 2] cycloadditions of alkylidenecyclopropanes. A straightforward entry to fused 6,7,5-tricyclic systems
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A highly diastereo- and chemoselective intramolecular nickel-catalyzed cycloaddition of alkene- and alkyne-tethered alkynylidenecyclopropanes is reported. The method constitutes the first fully intramolecular [3 + 2 + 2] alkylidenecyclopropropane cycloadd
- Saya, Luca,Fernndez, Israel,Lpez, Fernando,Mascareas, Jos L.
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- Palladium-catalyzed intramolecular iodine-transfer reactions in the presence of β-hydrogen atoms
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Atom economy: A palladium-catalyzed atom-transfer reaction of secondary alkyl iodides is described. An intramolecular double insertion of an alkyne and olefin provides access to primary iodides possessing β-hydrogen atoms. The process delivers these complex bicyclic homoallylic iodides with tetrasubstituted olefins from easily accessible aliphatic iodides. Different functional groups, including common heterocycles, are tolerated. Copyright
- Monks, Brendan M.,Cook, Silas P.
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- Click-Connected 2-(Hydroxyimino)aldehydes for the Design of UV-Responsive Functional Molecules
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Click chemistry is used to functionalize simple lipophilic and water-soluble molecules, a complex PEGylated phospholipid (DSPE-PEG2000), and two benzylic substrates with the 2-(hydroxyimino)aldehyde (HIA) group. To this end, two terminal alkynes bearing the HIA moiety were synthesized and coupled to different azides through copper(I)-catalyzed azide alkyne cycloaddition (CuAAC). Norrish–Yang photoisomerization (λ= 365 nm, LED source) is successfully obtained, with no interference by the triazole linker, except when the forbidden n-π* carbonyl transition is screened by a remote substituent such as salicylaldehyde. UV-Vis spectrometry suggests a specific interaction of HIAs with Cu(II), whereas no such evidence is found with Cu(I). We thereby show that the CuAAC methodology can be used successfully to obtain HIA-based UV-responsive hydrophilic or lipophilic ligands, phospholipidic components for the construction of liposomes, and macrocycle precursors.
- Carbonaro, Linda,Cort, Antonella Dalla,D'Acunzo, Francesca,Di Sabato, Antonio,Filippini, Dario,Gentili, Patrizia,Leonelli, Francesca,Mancini, Laura
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- Polymer supported cobalt carbonyl complexes as novel traceless alkyne linkers for solid-phase synthesis
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The immobilisation of functionalised alkynes onto 'polymer-bound triphenylphosphine', their chemical manipulation and subsequent release has been demonstrated for the first time, thus illustrating that cobalt carbonyl complexes can be used as 'traceless' π-alkyne linkers.
- Comely, Alex C.,Gibson, Susan E.,Hales, Neil J.
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Read Online
- Harnessing Redox Cross-Reactivity to Profile Distinct Cysteine Modifications
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Cysteine S-nitrosation and S-sulfination are naturally occurring post-translational modifications (PTMs) on proteins induced by physiological signals and redox stress. Here we demonstrate that sulfinic acids and nitrosothiols react to form a stable thiosulfonate bond, and leverage this reactivity using sulfinate-linked probes to enrich and annotate hundreds of endogenous S-nitrosated proteins. In physiological buffers, sulfinic acids do not react with iodoacetamide or disulfides, enabling selective alkylation of free thiols and site-specific analysis of S-nitrosation. In parallel, S-nitrosothiol-linked probes enable enrichment and detection of endogenous S-sulfinated proteins, confirming that a single sulfinic acid can react with a nitrosothiol to form a thiosulfonate linkage. Using this approach, we find that hydrogen peroxide addition increases S-sulfination of human DJ-1 (PARK7) at Cys106, whereas Cys46 and Cys53 are fully oxidized to sulfonic acids. Comparative gel-based analysis of different mouse tissues reveals distinct profiles for both S-nitrosation and S-sulfination. Quantitative proteomic analysis demonstrates that both S-nitrosation and S-sulfination are widespread, yet exhibit enhanced occupancy on select proteins, including thioredoxin, peroxiredoxins, and other validated redox active proteins. Overall, we present a direct, bidirectional method to profile select redox cysteine modifications based on the unique nucleophilicity of sulfinic acids.
- Majmudar, Jaimeen D.,Konopko, Aaron M.,Labby, Kristin J.,Tom, Christopher T. M. B.,Crellin, John E.,Prakash, Ashesh,Martin, Brent R.
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- A Ring Closing Metathesis Approach to the Formal Synthesis of (+)-Callyspongiolide
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An enantioselective synthesis of macrocyclic core of (+)-callyspongiolide is described, constituting a formal synthesis of this natural product. The synthetic strategy constructs the 14-membered macrocyclic domain via Yamaguchi esterification followed by a challenging ring-closing metathesis (RCM) to effect the final formation of the macrolactone.
- Ko, Kwang-Yoon,Wilson, Zoe E.,Furkert, Daniel P.,Brimble, Margaret A.
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Read Online
- Synthesis of the C1-C27 Fragment of Stambomycin D Validates Modular Polyketide Synthase-Based Stereochemical Assignments
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The stambomycins are a family of bioactive macrolides isolated from Streptomyces ambofaciens. Aside from two stereocenters installed through cytochrome P450 oxidations, their stereochemistry has been predicted by sequence analysis of the polyketide synthase. We report a synthesis of the C1-C27 fragment of stambomycin D, the spectroscopic data of which correlates well with that of the natural product, further validating predictive sequence analysis as a powerful tool for stereochemical assignment of complex polyketide natural products.
- Anderson, Edward A.,Bernasconi, Alice,Blanco, Araceli,Challis, Gregory L.,Chintalapudi, Venkaiah,Gudmundsson, Haraldur G.,Lim, Jieyan,Song, Lijiang,Tran, Minh
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supporting information
p. 7439 - 7444
(2021/10/01)
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- Synthesis of α,β-unsaturated epoxy ketones utilizing a bifunctional sulfonium/phosphonium ylide
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Herein, a new protocol for rapid synthesis of α,β-unsaturated epoxy ketones utilizing a bifunctional sulfonium/phosphonium ylide is described. This approach comprises two sequential chemoselective reactions between sulfonium and phosphonium ylides and two distinct aldehydes, which allows for the rapid construction of a variety of unsymmetric α,β-unsaturated epoxy ketones. This methodology allows the rapid construction of the core reactive functionality of a family of lipid peroxidation products, the epoxyketooctadecenoic acids, but can be further broadly utilized as a useful synthon for the synthesis of natural products, particularly those derived from oxidized fatty acids. Accordingly, a protocol utilizing this approach to synthesize the epoxyketooctadecenoic acid family of molecules is described.
- Eskandari, Roozbeh,Hess, Jeremy P.,Tochtrop, Gregory P.
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supporting information
p. 7136 - 7139
(2021/07/28)
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- Anodic Oxidation of Aminotetrazoles: A Mild and Safe Route to Isocyanides
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A new electrochemical method for the preparation of isocyanides from easily accessible aminotetrazole derivatives has been developed, which tolerates an unprecedented range of functional groups. The use of chemical, rather than electrochemical, oxidation to afford isocyanides was also demonstrated, which provides access to these compounds for those without electrosynthesis equipment. The practicality of scale-up using flow electrochemistry has been demonstrated, in addition to the possibility of using electrochemically generated isocyanides in further reactions.
- Leech, Matthew C.,Petti, Alessia,Tanbouza, Nour,Mastrodonato, Andrea,Goodall, Iain C. A.,Ollevier, Thierry,Dobbs, Adrian P.,Lam, Kevin
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supporting information
p. 9371 - 9375
(2021/12/09)
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- Synthesis of an Alkynyl Methylglyoxal Probe to Investigate Nonenzymatic Histone Glycation
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Methylglyoxal (MGO) is a reactive dicarbonyl metabolite that modifies histones in vivo and induces changes in chromatin structure and function. Here we report the synthesis and application of a chemical probe for investigating MGO-glycation. A two-step synthesis of a Cu-click compatible alkynyl oxoaldehyde probe (AlkMGO) via sequential Dess-Martin and Riley oxidations is presented. This synthesis elevates the accessibility and utility of an important tool for tracking, enriching, and studying MGO-glycation to aid in understanding its underlying biochemical functions.
- David, Yael,Guber, David,Maksimovic, Igor,Upad, Akhil,Zheng, Qingfei
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- TUBULYSINS AND PROTEIN-TUBULYSIN CONJUGATES
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Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with cancer, including tubulysins and protein (e.g., antibody) drug conjugates thereof.
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Paragraph 0014; 00348
(2020/07/14)
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- Highly efficient and practical aerobic oxidation of alcohols by inorganic-ligand supported copper catalysis
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The oxidation of alcohols to aldehydes or ketones is a highly relevant conversion for the pharmaceutical and fine-chemical industries, and for biomass conversion, and is commonly performed using stoichiometric amounts of highly hazardous oxidants. The aerobic oxidation of alcohols with transition metal complex catalysts previously required complicated organic ligands and/or nitroxyl radicals as co-catalysts. Herein, we report an efficient and eco-friendly method to promote the aerobic oxidation of alcohols using an inorganic-ligand supported copper catalyst 1, (NH4)4[CuMo6O18(OH)6], with O2 (1 atm) as the sole oxidant. Catalyst 1 is synthesized directly from cheap and commonly available (NH4)6Mo7O24·4H2O and CuSO4, which consists of a pure inorganic framework built from a central CuII core supported by six MoVIO6 inorganic scaffolds. The copper catalyst 1 exhibits excellent selectivity and activity towards a wide range of substrates in the catalytic oxidation of alcohols, and can avoid the use of toxic oxidants, nitroxyl radicals, and potentially air/moisture sensitive and complicated organic ligands that are not commercially available. Owing to its robust inorganic framework, catalyst 1 shows good stability and reusability, and the catalytic oxidation of alcohols with catalyst 1 could be readily scaled up to gram scale with little loss of catalytic activity, demonstrating great potential of the inorganic-ligand supported Cu catalysts in catalytic chemical transformations.
- Wei, Zheyu,Ru, Shi,Zhao, Qixin,Yu, Han,Zhang, Gang,Wei, Yongge
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supporting information
p. 4069 - 4075
(2019/08/07)
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- Compositions and methods for detecting S-nitrosylation and S-sulfinylation
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The present invention relates to methods for detecting protein S-sulfinylation and S-sulfinylation within thiol groups in proteins, metabolites, or materials.
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Page/Page column 19; 24; 25
(2019/09/23)
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- Labeling and Natural Post-Translational Modification of Peptides and Proteins via Chemoselective Pd-Catalyzed Prenylation of Cysteine
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The prenylation of peptides and proteins is an important post-translational modification observed in vivo. We report that the Pd-catalyzed Tsuji-Trost allylation with a Pd/BIPHEPHOS catalyst system allows the allylation of Cys-containing peptides and proteins with complete chemoselectivity and high n/i regioselectivity. In contrast to recently established methods, which use non-native connections, the Pd-catalyzed prenylation produces the natural n-prenylthioether bond. In addition, a variety of biophysical probes such as affinity handles and fluorescent tags can be introduced into Cys-containing peptides and proteins. Furthermore, peptides containing two cysteine residues can be stapled or cyclized using homobifunctional allylic carbonate reagents.
- Schlatzer, Thomas,Kriegesmann, Julia,Schr?der, Hilmar,Trobe, Melanie,Lembacher-Fadum, Christian,Santner, Simone,Kravchuk, Alexander V.,Becker, Christian F. W.,Breinbauer, Rolf
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supporting information
p. 14931 - 14937
(2019/10/11)
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- Nickel-Catalyzed Selective Reduction of Carboxylic Acids to Aldehydes
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The direct reduction of carboxylic acids to aldehydes is a fundamental transformation in organic synthesis. The combination of an air-stable Ni precatalyst, dimethyl dicarbonate as an activator, and silane reductant effects this reduction for a wide variety of substrates, including pharmaceutically relevant structures, in good yields and with no overreduction to alcohols. Moreover, this methodology is scalable, allows access to deuterated aldehydes, and is also compatible with one-pot utilization of the aldehyde products.
- Iosub, Andrei V.,Morav?ík, ?tefan,Wallentin, Carl-Johan,Bergman, Joakim
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supporting information
p. 7804 - 7808
(2019/10/14)
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- Highly practical and efficient preparation of aldehydes and ketones from aerobic oxidation of alcohols with an inorganic-ligand supported iodine catalyst
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Herein, we divulge an efficient protocol for aerobic oxidation of alcohols with an inorganic-ligand supported iodine catalyst, (NH4)5[IMo6O24]. The catalyst system is compatible with a wide range of groups and exhibits high selectivity, and shows excellent stability and reusability, thus serving as a potentially greener alternative to the classical transformations.
- Zhang, Mengqi,Zhai, Yongyan,Ru, Shi,Zang, Dejin,Han, Sheng,Yu, Han,Wei, Yongge
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supporting information
p. 10164 - 10167
(2018/09/13)
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- In(OTf)3-Catalyzed Cascade Cyclization for Construction of Oxatricyclic Compounds
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A highly diastereoselective cascade cyclization reaction has been developed for establishing a series of oxatricyclic compounds using Chan's diene and simple keto alkynal substrates with only 1 mol % of In(OTf)3 as the catalyst in 82-92% yields. The potential utility of this synthetic strategy has been demonstrated in model studies for the construction the core structures of 1α,8α:4α,5α-diepoxy-4,5-dihydroosmitopsin and cortistatin A.
- Bao, Wenli,Tao, Yezi,Cheng, Jiangqun,Huang, Junrong,Cao, Jingming,Zhang, Mengxun,Ye, Weijian,Wang, Bo,Li, Yang,Zhu, Lizhi,Lee, Chi-Sing
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supporting information
p. 7912 - 7915
(2019/01/04)
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- Thiyl radical-mediated cyclization of ω-alkynyl O-tert-butyldiphenylsilyloximes
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ω-Alkynyl O-tert-butyldiphenylsilyloximes, upon treatment with odorless 4-tert-butylbenzenethiol in the presence of azobisisobutyronitrile (AIBN) in refluxing benzene, underwent addition of a thiyl radical to the alkynyl group followed by radical cyclizat
- Shibata, Nina,Tsuchiya, Takahisa,Hashimoto, Yoshimitsu,Morita, Nobuyoshi,Ban, Shintaro,Tamura, Osamu
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supporting information
p. 3025 - 3034
(2017/04/10)
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- Visible-Light-Induced Efficient Selective Oxidation of Nonactivated Alcohols over {001}-Faceted TiO2 with Molecular Oxygen
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In the presence of molecular oxygen, a {001}-faceted nanocrystalline anatase TiO2 catalyst enabled the selective oxidation of nonactivated aliphatic alcohols to the corresponding aldehydes or ketones under visible light. The reaction shows excellent conversion and selectivity towards the formation of the carbonyl products without over-oxidation to the corresponding carboxylic acids. The exceptional reactivity of the catalyst is possibly due to the absorption of visible light originating from a stronger interaction of alcohol with the {001} facet, which facilitates the modification of the band structure of TiO2, thus facilitating the photogenerated hole transfer and subsequent oxidation processes. The experimental results have also been corroborated by first-principles quantum chemical DFT calculations.
- Vadakkekara, Raji,Biswas, Abul Kalam,Sahoo, Tapan,Pal, Provas,Ganguly, Bishwajit,Ghosh, Subhash Chandra,Panda, Asit Baran
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supporting information
p. 3084 - 3089
(2016/11/13)
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- Beta-lactones as antibacterial agents
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The present invention relates to specific beta-lactone compounds and compositions thereof for the treatment of infections, such as, e.g., infections with bacteria or infections with protozoa, in particular infections with Gram-positive and/or Gram-negativ
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Page/Page column 37
(2017/01/05)
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- Iron/ABNO-Catalyzed Aerobic Oxidation of Alcohols to Aldehydes and Ketones under Ambient Atmosphere
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We report a new Fe(NO3)3·9H2O/9-azabicyclo[3.3.1]nonan-N-oxyl catalyst system that enables efficient aerobic oxidation of a broad range of primary and secondary alcohols to the corresponding aldehydes and ketones at room temperature with ambient air as the oxidant. The catalyst system exhibits excellent activity and selectivity for primary aliphatic alcohol oxidation. This procedure can also be scaled up. Kinetic analysis demonstrates that C-H bond cleavage is the rate-determining step and that cationic species are involved in the reaction.
- Wang, Lianyue,Shang, SenSen,Li, Guosong,Ren, Lanhui,Lv, Ying,Gao, Shuang
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p. 2189 - 2193
(2016/03/15)
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- Bioinspired aerobic oxidation of alcohols with a bifunctional ligand based on bipyridine and TEMPO
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A novel bioinspired bifunctional ligand incorporating metal-binding site and stable free radical has been synthesized. The catalytic system obtained from the bifunctional ligand with copper(i) iodide in the presence of N-methylimidazole is highly efficient for the oxidation of a broad range of primary benzylic, allylic, alkynyl, aliphatic alcohols and secondary benzylic alcohols to the corresponding aldehydes and ketones in good to excellent yields. The catalyst system exhibits broad functional-group compatibility. The reaction is carried out in acetonitrile as solvent under air balloon at room temperature. The catalyst system features excellent activity for primary aliphatic alcohol oxidation and a high chemoselective oxidation of primary alcohols over the secondary alcohols. This oxidation process is readily amenable to larger-scale application. The interaction of the different components in the reaction mixtures was studied by UV-visible spectroscopy. The data indicated that Cu(i) existed throughout the reaction. A plausible mechanism of the catalytic cycle is proposed.
- Wang, Lianyue,Bie, Zhixing,Shang, Sensen,Lv, Ying,Li, Guosong,Niu, Jingyang,Gao, Shuang
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p. 35008 - 35013
(2016/05/19)
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- Prodrugs and drug-macromolecule conjugates having controlled drug release rates
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The present invention provides methods and compositions that permit controlled and prolonged drug release in vivo. The compounds are either prodrugs with tunable rates of release, or conjugates of the drug with macromolecules which exhibit tunable control
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Page/Page column 119; 120
(2016/08/17)
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- OXAZOLIDINONE HYDROXAMIC ACID COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
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This invention pertains generally to treating bacterial infections using organic compounds of Formula I. In certain aspects, the invention pertains to treating infections caused by Gram-negative bacteria. (I) wherein X, Y, R1, R2, R3, R4 and R5 and defined herein.
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Page/Page column 127
(2015/05/19)
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- A ring-closing enyne metathesis approach to functionalized semicyclic dienes: The total synthesis of (-)-tetrangomycin
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The angucycline antibiotic (-)-tetrangomycin was synthesized in 13 steps (11 % overall yield) by using a stereoselective Diels-Alder reaction between a naphthoquinone and a semicyclic diene to construct the benz[a]anthraquinone ring system. The diene inte
- Moodie, Lindon W. K.,Larsen, David S.
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supporting information
p. 1684 - 1694
(2014/03/21)
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- A Ring-Closing Enyne Metathesis Approach to Functionalized Semicyclic Dienes: The Total Synthesis of (-)-Tetrangomycin
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The angucycline antibiotic (-)-tetrangomycin was synthesized in 13 steps (11 % overall yield) by using a stereoselective Diels-Alder reaction between a naphthoquinone and a semicyclic diene to construct the benz[a]anthraquinone ring system. The diene inte
- Moodie, Lindon W. K.,Larsen, David S.
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supporting information
p. 1684 - 1694
(2015/10/05)
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- Anaerobic nitroxide-catalyzed oxidation of alcohols using the NO +/NO· redox pair
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A new method for alcohol oxidation using TEMPO or AZADO in conjunction with BF3·OEt2 or LiBF4 as precatalysts and tert-butyl nitrite as a stoichiometric oxidant has been developed. The system is based on a NO+/NO· pair for nitroxide reoxidation under anaerobic conditions. This allows the simple, high-yielding conversion of various achiral and chiral alcohols to carbonyl compounds without epimerization and no formation of nonvolatile byproducts.
- Holan, Martin,Jahn, Ullrich
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supporting information
p. 58 - 61
(2014/01/23)
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- HIGH MOLECULAR WEIGHT ZWITTERION-CONTAINING POLYMERS
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The present invention provides multi-armed high MW polymers containing hydrophilic groups and one or more functional agents, and methods of preparing such polymers.
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Paragraph 0424;0425
(2014/02/16)
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- Diastereoselective synthesis of highly substituted polycyclic scaffolds via a one-pot four-step tandem catalytic process
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A rapid and diastereoselective synthesis of highly substituted aminobicyclo[4.3.0]nonanes and bicyclo[4.4.0]decanes from alkyne derived allylic alcohols has been developed using a one-pot multi-bond forming tandem catalytic process. Overman rearrangement
- Grafton, Mark W.,Johnson, Stuart A.,Farrugia, Louis J.,Sutherland, Andrew
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p. 7133 - 7141
(2017/09/11)
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- The mechanism of caseinolytic protease (ClpP) inhibition
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Catch me if you can: The ClpP protease mediates protein homeostasis and can be efficiently inhibited by β-lactones. A combination of molecular docking, mutagenesis, activity-based protein profiling, and kinetics studies now reveals the mechanism of ClpP inhibition. A hydrophobic pocket next to the active site allows binding of long aliphatic and aromatic residues. The preferred stereoisomer binds into the oxyanion hole. Copyright
- Gersch, Malte,Gut, Felix,Korotkov, Vadim S.,Lehmann, Johannes,B?ttcher, Thomas,Rusch, Marion,Hedberg, Christian,Waldmann, Herbert,Klebe, Gerhard,Sieber, Stephan A.
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supporting information
p. 3009 - 3014
(2013/04/23)
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- Total synthesis of the Marine cyclic depsipeptide viequeamide A
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The first total synthesis of viequeamide A, a natural cyclic depsipeptide isolated from a marine button cyanobacterium, was achieved with the N-Me-Val-Thr peptide bond as the final macrocyclization site. The synthetic product gave nearly identical spectroscopic data to that reported for the natural product.
- Wang, Dongyu,Song, Shanshan,Tian, Ye,Xu, Youjun,Miao, Zehong,Zhang, Ao
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p. 974 - 978
(2013/07/05)
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- Total synthesis of (-)-hippodamine by stereocontrolled construction of azaphenalene skeleton based on extended one-pot asymmetric azaelectrocyclization
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The first asymmetric total synthesis of (-)-hippodamine has been accomplished via the concise construction of its azaphenalene core, which is featured by the 2,4,6-chiral piperidine synthesis based on one-pot asymmetric azaelectrocyclization in the partially activated substituent system and the subsequent intramolecular Mannich reaction.
- Fujita, Shintaro,Sakaguchi, Taku,Kobayashi, Toyoharu,Tsuchikawa, Hiroshi,Katsumura, Shigeo
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supporting information
p. 2758 - 2761
(2013/07/19)
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- Synthesis of amino-substituted indanes and tetralins via consecutive multibond-forming tandem processes
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A rapid and general approach for the synthesis of amino-substituted indanes and tetralins from readily available alkyne-derived allylic alcohols via consecutive multibond-forming tandem processes has been developed. In the first one-pot tandem process, a series of cyclic dienes were prepared using an Overman rearrangement under thermal conditions, followed by a ruthenium(II)-catalyzed ring closing enyne metathesis reaction. The resulting exo-dienes were then subjected to a second one-pot tandem process involving a highly regioselective Diels-Alder reaction with alkynes, quinones or nitriles and a subsequent oxidation step to give a diverse library of C-1 amino-substituted indanes and tetralins in good overall yields.
- Grafton, Mark W.,Farrugia, Louis J.,Sutherland, Andrew
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p. 7199 - 7207
(2013/08/23)
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- Synthesis of azomethine imines using an intramolecular alkyne hydrohydrazination approach
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Azomethine imines can be accessed upon heating appropriate alkynylhydrazide precursors. This simple thermal hydroamination approach allows the formation of five- and six-membered dipoles in modest to excellent yields. The structure of the acyl group is important to minimize side reactions and allow the isolation of the azomethine imines by column chromatography.
- Hunt, Ashley D.,Dion, Isabelle,Das Neves, Nicolas,Taing, Sandrine,Beauchemin, Andre M.
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p. 8847 - 8852
(2013/09/24)
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- SYNTHESIS, STRUCTURE AND USE OF FUNCTIONALIZED NAPHTHALENES
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Methods for the synthesis and use of functionalized, substituted naphthalenes are described. The functionalized, substituted naphthalenes display useful properties including liquid crystals and fluorescence properties, such as solvatochromatic fluorescenc
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Paragraph 0070
(2013/12/03)
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- Tyrosine specific sequential labeling of proteins
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We report (a) on the synthesis of a long-wavelength fluorescent coumarin containing an allyloxy acetate moiety, (b) the synthesis of two linkers containing an allyloxy acetate and an alkyne or azide function, respectively, and (c) the selective modification human serum albumin by a sequential method involving Pd(II) catalyzed modification of the phenolic side chain of tyrosine residues with an alkyne bearing linker and a subsequent azide-alkyne click reaction with an azide functionalized long-wavelength emitting coumarin dye. The method is likely to be applicable to various kinds of azido-modified fluorophores, and the Pd(II)-catalyzed modification of the tyrosines may also be used to introduce other kinds of tags. With these reagents, tyrosine specific modulation of proteins and peptides becomes possible either directly or in a sequential manner.
- Cserép, Gergely B.,Herner, András,Wolfbeis, Otto S.,Kele, Péter
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supporting information
p. 5776 - 5778
(2013/10/22)
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- Rhodium-catalyzed intra- and intermolecular [5 + 2] cycloaddition of 3-acyloxy-1,4-enyne and alkyne with concomitant 1,2-acyloxy migration
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A new type of rhodium-catalyzed [5 + 2] cycloaddition was developed for the synthesis of seven-membered rings with diverse functionalities. The ring formation was accompanied by a 1,2-acyloxy migration event. The five- and two-carbon components of the cycloaddition are 3-acyloxy-1,4-enynes (ACEs) and alkynes, respectively. Cationic rhodium(I) catalysts worked most efficiently for the intramolecular cycloaddition, while only neutral rhodium(I) complexes could facilitate the intermolecular reaction. In both cases, electron-poor phosphite or phosphine ligands often improved the efficiency of the cycloadditions. The scope of ACEs and alkynes was investigated in both the intra- and intermolecular reactions. The resulting seven-membered-ring products have three double bonds that could be selectively functionalized.
- Shu, Xing-Zhong,Li, Xiaoxun,Shu, Dongxu,Huang, Suyu,Schienebeck, Casi M.,Zhou, Xin,Robichaux, Patrick J.,Tang, Weiping
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scheme or table
p. 5211 - 5221
(2012/05/05)
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- Palladium-catalyzed cascade process to construct 1,2,5-trisubstituted pyrroles
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A novel palladium-catalyzed cascade allylic amination/intramolecular hydroamination/isomerization process of protected enynol 1 and primary amine 2 has been explored, which constructs the important 1,2,5-trisubstituted pyrroles. This transformation offers an alternative synthetic methodology capable of generating substituted pyrroles in a straightforward way.
- Zhang, Yong-Qiang,Zhu, Dao-Yong,Li, Bao-Sheng,Tu, Yong-Qiang,Liu, Ji-Xin,Lu, Yong,Wang, Shao-Hua
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supporting information; experimental part
p. 4167 - 4170
(2012/06/18)
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- Efficient entry to the [2.2.2]-diazabicyclic ring system via diastereoselective domino reaction sequence
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A domino reaction sequence involving aldol condensation, alkene isomerization, and intramolecular hetero-Diels-Alder cycloaddition for the synthesis of [2.2.2]-diazabicyclic structures is reported. Excellent diastereofacial control during the cycloaddition is enforced with a removable chiral phenyl aminal diketopiperazine substituent. The reaction sequence rapidly generates molecular complexity and is competent with both enolizable and nonenolizable aldehyde substrates (nine examples total). Progress toward the synthesis of malbrancheamide B, a protypical member of the [2.2.2]-diazabicyclic natural product family, is also disclosed.
- Margrey, Kaila A.,Chinn, Alex J.,Laws, Stephen W.,Pike, Robert D.,Scheerer, Jonathan R.
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supporting information; experimental part
p. 2458 - 2461
(2012/07/27)
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- Discovery of a multi-bond forming, four-step tandem process: Construction of drug-like polycyclic scaffolds
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A one-pot tandem process involving an Overman rearrangement, ring closing enyne metathesis and a hydrogen bonding directed Diels-Alder reaction has been developed for the efficient diastereoselective synthesis of functionalised amino substituted tetralin and indene ring systems.
- Grafton, Mark W.,Farrugia, Louis J.,Senn, Hans Martin,Sutherland, Andrew
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supporting information; experimental part
p. 7994 - 7996
(2012/09/08)
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- A thermal dehydrogenative Diels-Alder reaction of styrenes for the concise synthesis of functionalized naphthalenes
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Functionalized naphthalenes are valuable building blocks in many important areas. A microwave-assisted, intramolecular dehydrogenative Diels-Alder reaction of styrenyl derivatives to provide cyclopenta[b]naphthalene substructures not previously accessible using existing synthetic methods is described. The synthetic utility of these uniquely functionalized naphthalenes was demonstrated by a single-step conversion of one of these cycloadducts to a fluorophore bearing a structural resemblance to Prodan.
- Kocsis, Laura S.,Benedetti, Erica,Brummond, Kay M.
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supporting information
p. 4430 - 4433
(2012/10/29)
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- Modification of Factor VIII
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A Factor VIII derivative of formula (I): wherein: B represents C2 to C10 alkylene; m represents 0 or an integer from 1 to 19, n represents an integer from 1 to 20, and the sum of m and n is from 1 to 20; P represents a mono or polyradical of Factor VIII obtained by removing m+n carbamoyl groups from the side chains of glutamine residues in Factor VIII; and M represents a moiety (M1) that increases the plasma half-life of the Factor VIII derivative or a reporter moiety (M2); or a pharmaceutically acceptable salt thereof.
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- Molecular editing and assessment of the cytotoxic properties of iejimalide and progeny
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Systematic variation of all substructures embedded into the framework of iejimalide B (2) led to a panel of synthetic analogues of this polyunsaturated macrolide, featuring structural modifications that are not accessible by derivatization of the natural lead compound itself. The assessment of the cytotoxicity of these compounds with the aid of a monolayer proliferation assay (12 human tumor cell lines in vitro) as well as a colony formation assay (24 human tumor xenografts ex vivo) revealed the exceptional potency of 2 and several of its synthetic congeners, with IC50 values in the picomolar range for the most sensitive cell lines. Whereas structural modifications of the macrocycle or of the side chain generally lead to a decrease in activity, changes of the peptidic terminus are not only well accommodated but engender increased tumor selectivity as well. 2 and two of the most promising analogues were selected for in vivo studies in mice, in which their activity against human tumor xenografts of breast cancer (MAXF 401) and prostate cancer (PRXF PC-3M) was tested. In contrast to a previous report in the literature however, which had claimed in vivo activity for the parent iejimalides, these tests did not show a significant therapeutic effect against the chosen solid tumors upon intraperitoneal administration. Copyright
- Gagnepain, Julien,Moulin, Emilie,Nevado, Cristina,Waser, Mario,Maier, Armin,Kelter, Gerhard,Fiebig, Heinz-Herbert,Fuerstner, Alois
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supporting information; experimental part
p. 6973 - 6984
(2011/07/30)
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- A modular synthesis of salvileucalin B structural domains
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A modular strategy leading to the salvileucalin B core structure has been accomplished. The developed synthetic strategy featured a bioinspired intramolecular Diels-Alder reaction to construct domain "A", REDOX chemistry to functionalize domain "B", and a palladium-mediated cross-coupling to install domain "C". This flexible approach should facilitate further chemical and biological investigations of this fascinating class of compounds.
- Tseng, Chih-Chung,Ding, Hanfeng,Li, Ang,Guan, Yucui,Chen, David Y.-K.
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supporting information; experimental part
p. 4410 - 4413
(2011/10/09)
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- Direct acylation of carrier proteins with functionalized β-lactones
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As the key component of many biosynthetic assemblies, acyl-carrier proteins offer a robust entry point for introduction of small molecule probes and pathway intermediates. Current labeling strategies primarily rely on modifications to the phosphopantethei
- Amoroso, Jon W.,Borketey, Lawrence S.,Prasad, Gitanjeli,Schnarr, Nathan A.
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supporting information; experimental part
p. 2330 - 2333
(2010/10/03)
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- Novel radical cyclization method accompanied by elimination of hydrazyl radical
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The potential of hydrazine group as the new radical leaving group was studied. Radical cyclization of (E)-1,1-dialkyl-2-(1-alkyloct-2-en-7-ynyl) hydrazines with n-Bu3SnH/AIBN, followed by protodestannylation, gave 1-alkenyl-2-methylenecyclopent
- Kobayashi, Shoji,Hirao, Hidefumi,Kawauchi, Tatsuro,Ryu, Ilhyong
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scheme or table
p. 879 - 885
(2010/10/02)
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- Stereoselective synthesis of (+)-euphococcinine and (-)-adaline
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(Chemical Equation Presented) We describe the syntheses of (+)-euphococcinine and (-)-adaline, two naturally occurring alkaloids containing a quaternary carbon bearing a nitrogen atom. Key features of the syntheses are a 3,3-sigmatropic rearrangement to give an all-carbon quaternary center, a ring-closing alkene metathesis to give an 8-membered ring, and the use of a single enantiomer of p-menthane-3-carboxaldehyde to make two natural alkaloids of opposite configuration.
- Arbour, Melissa,Roy, Stephanie,Godbout, Cedrickx,Spino, Claude
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supporting information; experimental part
p. 3806 - 3814
(2009/09/25)
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- Synthesis of pyridines and pyrazines using an intramolecular hydroamination-based reaction sequence
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A management issue! Various pyridines and pyrazines can be efficiently accessed from simple acyclic precursors using an intramolecular hydroamination/isomerization/aromatization sequence (see scheme). ρ-Toluenesulfonic acid (2 mol%) is used to catalyze this novel alkyne annulation, in which the oxime group allows for a subsequent redoxneutral aromatization step to occur.
- Rizk, Toni,Bilodeau, Eric J.-F.,Beauchemin, Andre M.
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supporting information; experimental part
p. 8325 - 8327
(2010/01/16)
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- β-lactones as privileged structures for the active-site labeling of versatile bacterial enzyme classes
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(Chemical Equation Presented) A chemical proteomic strategy has been applied directly to bacterial proteomes, and b-lactones have been identified as important natural product derivatives with a high affinity to various enzyme classes (see picture). This a
- Boettcher, Thomas,Sieber, Stephan A.
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supporting information; experimental part
p. 4600 - 4603
(2009/02/08)
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- Exploiting domino enyne metathesis mechanisms for skeletal diversity generation
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In the context of diversity-oriented synthesis, the exploration and optimization of the domino metathesis of decorated norbornenes allowed complex polycyclic architectures to be generated in a highly efficient and atom-economical process. The Royal Society of Chemistry.
- Spandl, Richard J.,Rudyk, Helene,Spring, David R.
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supporting information; experimental part
p. 3001 - 3003
(2009/02/04)
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