- Conformations of Oxocane
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Conformational analysis of oxocane (oxacyclooctane) has been examined by molecular mechanics (MM2), variable-temperature 13C NMR, and lanthanide-induced shift (LIS) 1H and 13C NMR.MM2 calculations find the BC-3 conformer and its enantiomer BC-7 to be favored, with the four next best forms and their energies relative to BC-3-being BC-1 (1.1 kcal/mol), TBC-1(1.1), BC-4(1.5), and TCC-1(1.6).Barriers to pseudorotational interconversion of BC-3 and BC-7 are calculated to be 5.0 kcal/mol through BC-5 and 6.7 kcal/mol through BC-1.The former would allow fast BC-3/BC-7 equilibration even at -170 deg C, which would leave reported low-temperature 1H NMR spectra compatible with a BC-3 structure as well as BC-1.Calculated barriers for BC ring inversion and interconversion of the BC family with the crown family (TCC-1) are 8.2 and 8.5 kcal/mol, respectively.A new two-step synthesis of oxocane and its 2,2,7,7-d4 analogue is reported, the latter allowing unequivocal assignment of chemical shifts. 13C NMR spectra of oxocane between 138 and 290 K show BC-family/crown-family inter-conversion in the vicinity of 215 K (ΔG(excit.) = 10.0 +/- 0.3 kcal/mol), with the crown family comprising 4percent of the equilibrium at 174 K (ΔG0 = 1.1 +/- 0.1 kcal/mol).The 1H and 13C LIS induced by Yb(fod)3 on oxocane agree well with BC-3 and BC-7 being the predominant conformers at room temperature but do not acceptably fit a BC-1 structure.Thus, all available data from calculation and experiment are in accord with BC-3 being the favored conformation of oxocane.
- Meyer, Walter L.,Taylor, Patterson W.,Reed, Scott A.,Leister, Marvin C.,Schneider, Hans-Joerg,et al.
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Read Online
- Microwave-assisted polymer chemistry: Heck-reaction, transesterification, Baeyer-Villiger oxidation, oxazoline polymerization, acrylamides, and porous materials
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Several questions are still open concerning the different effects of microwave (MW) irradiation in organic and macromolecular chemistry. Analyzing experimental results on a relatively broad investigation area, we came to elucidate three main effects of microwave irradiation: efficient non-contact heating, an accelerating effect, and what we term a special effect. In this paper, we report the first MW-assisted synthesis of poly(2,5-dibutoxy-1,4-phenylenevinylene) via Heck-polycondensation as an example for efficient heating. The facile synthesis of the higher lactones 1-oxa-2-oxocyclooctanone and 1-oxa-2-oxocyclononanone via Baeyer-Villiger reaction offers indeed an example for the MW-accelerating effect. A survey of our recent work is also given to explain the effects more in detail and to provide examples of the special MW effect.
- Koopmans, Carsten,Iannelli, Mauro,Kerep, Patrick,Klink, Michael,Schmitz, Sarah,Sinnwell, Sebastian,Ritter, Helmut
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Read Online
- A Polyketide Cyclase That Forms Medium-Ring Lactones
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Medium-ring lactones are synthetically challenging due to unfavorable energetics involved in cyclization. We have discovered a thioesterase enzyme DcsB, from the decarestrictine C1 (1) biosynthetic pathway, that efficiently performs medium-ring lactonizations. DcsB shows broad substrate promiscuity toward linear substrates that vary in lengths and substituents, and is a potential biocatalyst for lactonization. X-ray crystal structure and computational analyses provide insights into the molecular basis of catalysis.
- Gao, De-Wei,Jamieson, Cooper S.,Wang, Gaoqian,Yan, Yan,Zhou, Jiahai,Houk,Tang, Yi
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- PEGylated Poly-HDACi: A Designer Polyprodrug from Optimized Drug Units**
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We designed, synthesized, and characterized a tri-block copolymer. Its hydrophobic part, a chain of histone deacetylase inhibitor (HDACi) prodrug, was symmetrically flanked by two identical PEG blocks, whereas the built-in HDACi was a linear molecule, terminated with a thiol at one end, and a hydroxyl group at the other. Such a feature facilitated end-to-end linkage of prodrugs through alternatively aligned disulfides and carbonates. The disulfides served dual roles: redox sensors of smart nanomedicine, and warheads of masked HDACi drugs. This approach, carefully designed to benefit both control-release and efficacy, is conceptually novel for optimizing drug units in nanomedicine. Micelles from this designer polyprodrug released only PEG, CO2 and HDACi, and synergized with DOX against HCT116 cells, demonstrating its widespread potential in combination therapy. Our work highlights, for the first time, the unique advantage of thiol-based drug molecules in nanomedicine design.
- Han, Jinghua,Huang, Qingqing,Kang, Yanke,Li, Jing,Luo, Zihan,Lv, Wenhui,Meng, Li,Shen, Jie,Wang, Da-Yuan,Wang, Peng George,Wang, Qiuyu,Wang, Yajie,Wang, Yanming
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supporting information
(2021/12/22)
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- Green Oxidation of Ketones to Lactones with Oxone in Water
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Cyclic ketones were quickly and quantitatively converted to 5-, 6-, and 7-membered lactones, very important synthons, by treatment with Oxone, a cheap, stable, and nonpollutant oxidizing reagent, in 1 M NaH2PO4/Na2HPO4 water solution (pH 7). Under such simple and green conditions, no hydroxyacid was formed, thus making the adoption of more complex and non-eco-friendly procedures previously developed to avoid lactone hydrolysis unnecessary. With some changes, the method was successfully applied also to water-insoluble ketones such as adamantanone, acetophenone, 2-indanone, and the challenging cycloheptanone.
- Bertolini, Valentina,Appiani, Rebecca,Pallavicini, Marco,Bolchi, Cristiano
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p. 15712 - 15716
(2021/11/01)
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- Ynamide-Mediated Macrolactonization
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Macrolactonization represents a long-standing challenge for organic chemists. Herein, an ynamide-mediated macrolactonization of seco-acids with the assistance of an acid catalyst is described. Various macrolactones ranging in ring size from medium to large can be prepared by using this method. The notorious issues associated with conventional macrolactonization reactions, such as the racemization/epimerization of seco-acids containing an α-chirality center, and the E/Z isomerization of α,β-unsaturated seco-acids can be avoided using this method. In addition, the ynamide-mediated two-step macrolactonization reaction can be performed in a one-pot manner, thus offering a user-friendly protocol. Cyclodepsipeptides containing both amide and ester bonds can also be constructed using this method as the key step to facilitate the ring closure. The total synthesis of dehydroxy LI-F04a, which contains a cyclic hexadepsipeptide core, has been accomplished using this method.
- Wang, Xuewei,Yang, Ming,Zhao, Junfeng
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p. 5230 - 5235
(2020/05/27)
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- LIPID PRODRUGS OF BTK INHIBITORS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00405; 00560; 00561
(2020/09/12)
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- LIPID PRODRUGS OF GLUCOCORTICOIDS AND USES THEREOF
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, and methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a disclosed lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00544; 00545
(2020/09/12)
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- Stereoselective synthesis of MaR2n-3 DPA
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The first total synthesis of the n-3 docosapentaenoic derived oxygenated product MaR2n-3 DPA has been achieved. The 13R and 14S stereogenic centers were introduced using 2-deoxy-D-ribose in a chiral pool strategy. The geometry of the Z,E,E-triene moiety was prepared using highly E-selective Wittig- and Takai-olefination reactions as well as the Z-stereoselective Lindlar reduction. LC/MS-MS data of synthetic MaR2n-3 DPA matched data for the biosynthetic formed product that enabled the configurational assignment of this oxygenated natural product to be (7Z,9E,11E,13R,14S,16Z,19Z)-13,14-dihydroxydocosa-7,9,11,16,19-pentaenoic acid.
- S?nderskov, Jeanne,Tungen, J?rn E.,Palmas, Francesco,Dalli, Jesmond,Serhan, Charles N.,Stenstr?m, Yngve,Vidar Hansen, Trond
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supporting information
(2019/12/24)
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- INHIBITORS OF HISTONE DEACETYLASE USEFUL FOR THE TREATMENT OR PREVENTION OF HIV INFECTION
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The present invention relates to Compounds of Formula (I): Formula (I) and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, R3, Ra, Rb, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula (I), and methods of using the compounds of Formula (I) for treating or preventing HIV infection in a subject.
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Page/Page column 39
(2020/02/23)
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- Photoenzymatic Generation of Unstabilized Alkyl Radicals: An Asymmetric Reductive Cyclization
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Flavin-dependent "ene"-reductases can generate stabilized alkyl radicals when irradiated with visible light; however, they are not known to form unstabilized radicals. Here, we report an enantioselective radical cyclization using alkyl iodides as precursors to unstabilized nucleophilic radicals. Evidence suggests this species is accessed by photoexcitation of a charge-transfer complex that forms between flavin and substrate within the protein active site. Stereoselective delivery of a hydrogen atom from the flavin semiquinone to the prochiral radical formed after cyclization provides high levels of enantioselectivity across a variety of substrates. Overall, this transformation demonstrates that photoenzymatic catalysis can address long-standing selectivity challenges in the radical literature.
- Clayman, Phillip D.,Hyster, Todd K.
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supporting information
p. 15673 - 15677
(2020/10/18)
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- ε-Caprolactone manufacture via efficient coupling Baeyer-Villiger oxidation with aerobic oxidation of alcohols
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To avoid the use of peracids oxidant or highly concentrated hydrogen peroxide which is potentially hazardous and explosive, herein, a new route to ε-caprolactone was developed in which molecule oxygen was employed as the terminal oxidant. The commercial available N-hydroxyphthalimide and ammonium cerium nitrate were used as the key catalysts for the increased yield of ε-caprolactone. For instance, the selectivity of ε-caprolactone was obtained 92 % with 85 % conversion of cyclohexanone which was comparable to the strategies using highly concentrated hydrogen peroxide. The sacrificed alcohols were transformed into corresponding ketones which were also valuable chemicals. Furthermore, the efficiency of the alcohols was achieved to unprecedented 52 %. The Baeyer-Villiger oxidation of various other cycloalkanones was also examined. The substituent group effect on the efficiency of sacrificed alcohols was investigated in which weak electron-donating substituent induced nearly quantitative yield of ε-caprolactone. The reaction mechanism was studied with the help of electron paramagnetic resonance which indicated the existence of a radical pathway.
- Du, Renfeng,Li, Haoran,Wang, Yongtao,Yao, Jia,Yuan, Haoran,Zhao, Chenxuan
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- Method for preparing lactone compound by cycloalkane compound through oxidation
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The invention discloses a method for preparing a lactone compound by a cycloalkane compound through oxidation. The method comprises the following steps of using the cycloalkane compound as the raw material, and further oxidizing by a catalysis system under the oxygen-containing atmosphere, so as to obtain the lactone compound, wherein the catalysis system comprises a catalyst and an additive; thecatalyst is selected from a cyclic organic nitrogen and oxygen free radical precursor in formulas (I), (II), (III) and (IV); in the formula, R1, R2 and R3 are independently selected from hydrogen atom, alkyl, cycloalkyl, aryl, heterocycle, hydroxyl, nitryl, or halogen, or at least two of R1, R2 and R3 form loops; the additive is selected from an aldehyde compound. The preparation method has the advantages that the corresponding lactone is prepared by the cycloalkane compound through a one-step method; the conditions are mild, the safety is high, and the metal catalytic oxidization is avoided;the selectivity of the target product, namely the lactone compound, is high. The formulae are shown in the description.
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Paragraph 0064; 0065; 0116-0119
(2019/02/04)
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- LYMPHATIC SYSTEM-DIRECTING LIPID PRODRUGS
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The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a provided lipid prodrug or a pharmaceutical composition thereof.
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Paragraph 00518; 00519
(2019/03/17)
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- Investigation of (S)-(-)-acidomycin: A selective antimycobacterial natural product that inhibits biotin synthase
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The synthesis, absolute stereochemical configuration, complete biological characterization, mechanism of action and resistance, and pharmacokinetic properties of (S)-(-)-acidomycin are described. Acidomycin possesses promising antitubercular activity against a series of contemporary drug susceptible and drug-resistant M. tuberculosis strains (minimum inhibitory concentrations (MICs) = 0.096-6.2 μM) but is inactive against nontuberculosis mycobacteria and Gram-positive and Gram-negative pathogens (MICs > 1000 μM). Complementation studies with biotin biosynthetic pathway intermediates and subsequent biochemical studies confirmed acidomycin inhibits biotin synthesis with a Ki of approximately 1 μM through the competitive inhibition of biotin synthase (BioB) and also stimulates unproductive cleavage of S-adenosyl-l-methionine (SAM) to generate the toxic metabolite 5′-deoxyadenosine. Cell studies demonstrate acidomycin selectively accumulates in M. tuberculosis providing a mechanistic basis for the observed antibacterial activity. The development of spontaneous resistance by M. tuberculosis to acidomycin was difficult, and only low-level resistance to acidomycin was observed by overexpression of BioB. Collectively, the results provide a foundation to advance acidomycin and highlight BioB as a promising target.
- Bockman, Matthew R.,Engelhart, Curtis A.,Cramer, Julia D.,Howe, Michael D.,Mishra, Neeraj K.,Zimmerman, Matthew,Larson, Peter,Alvarez-Cabrera, Nadine,Park, Sae Woong,Boshoff, Helena I. M.,Bean, James M.,Young, Victor G.,Ferguson, David M.,Dartois, Veronique,Jarrett, Joseph T.,Schnappinger, Dirk,Aldrich, Courtney C.
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p. 598 - 617
(2019/02/14)
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- Expanding the substrate scope of phenylacetone monooxygenase from Thermobifida fusca towards cyclohexanone by protein engineering
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Baeyer-Villiger monooxygenases (BVMOs) convert ketones into lactones that have important applications in polymer synthesis. Here we report on expanding the substrate scope of a thermostable phenylacetone monooxygenase (PAMO) to cyclohexanone by using site-directed mutagenesis. Several new mutants were found to be active with cyclohexanone for which wild-type PAMO shows no activity. The best mutants could convert 10 mM cyclohexanone completely within 12 h, and their catalytic properties were characterized subsequently. In addition to cyclohexanone, several other cyclic ketones were also identified as substrate for the new evolved mutants. These results expand the biocatalytic toolbox for further feasible applications.
- Yang, Guang,Cang, Ran,Shen, Li-Qun,Xue, Feng,Huang, He,Zhang, Zhi-Gang
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p. 159 - 163
(2018/11/21)
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- Asymmetric Synthesis of Chiral 1,3-Dimethyl Units Through a Double Michael Reaction of Nitromethane and Crotonaldehyde Catalyzed by Diphenylprolinol Silyl Ether
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An efficient synthetic route to install chiral 1,3-dimethyl units through a double Michael reaction of crotonaldehyde and nitromethane catalyzed by diphenylprolinol silyl ether is developed. Either 1,3- syn - or 1,3- anti -dimethyl units are obtained selectively depending on the enantiomer of the diphenylprolinol silyl ether catalyst used. The side chain of pneumocandin B 0 is synthesized enantioselectively by using the present method as a key step.
- Hayashi, Yujiro,Toda, Shunsuke
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supporting information
p. 442 - 448
(2019/02/26)
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- Alkyne amide-mediated one-pot method for preparing macrolide
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The invention discloses a method for preparing macrolide by using alkyne amide as a condensation reagent and hydroxy carboxylic acid as a raw material at 10-50 DEG C; the method comprises a method formildly and efficiently preparing an alpha-acyloxy alkenyl amide compound through addition of carboxylic acid and alkyne amide at room temperature under the catalysis of cuprous salt and a method forobtaining macrocyclic lactonization through enabling the intramolecular hydroxyl of the alpha-acyloxy alkenyl amide compound to react under the catalysis of p-toluenesulfonic acid; the two reactions can be performed through a one-pot method as well, i.e., an intermediate alpha-acyloxy alkenyl amide obtained after complete reaction of carboxylic acid and the alkyne amide does not need to be separated, the p-toluenesulfonic acid is directly added to perform intramolecular condensation reaction in the next step, thereby realizing the formation of the alkyne amide-mediated macrocyclic lactonization at room temperature. The method disclosed by the invention has the characteristics of mild reaction condition, simplicity and easy operation.
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- Cobalt-entrenched N-, O-, and S-tridoped carbons as efficient multifunctional sustainable catalysts for base-free selective oxidative esterification of alcohols
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We report the synthesis of sustainable and reusable non-noble transition-metal (cobalt) nanocatalysts containing N-, O-, and S-tridoped carbon nanotube (Co@NOSC) composites. The expensive and benign carrageenan served as the source of carbon, oxygen, and sulfur, whereas urea served as the nitrogen source. The material was prepared via direct mixing of precursors and freeze-drying followed by carbonization under nitrogen at 900 °C. Co@NOSC catalysts comprising a Co inner core and outer electron-rich heteroatom-doped carbon shell were thoroughly characterized using various techniques, namely, TEM, HRTEM, STEM elemental mapping, XPS, BET, and ICP-MS. The utility of the Co@NOSC catalyst was explored for base-free selective oxidative esterification of alcohols to the corresponding esters under mild reaction conditions; excellent conversions (up to 97%) and selectivities (up to 99%) were discerned. Furthermore, the substrate scope was explored for the cross-esterification of benzyl alcohol with long-chain alcohols (up to 98%) and lactonization of diols (up to 68%). The heterogeneous nature and stability of the catalyst facilitated by its ease of separation for long-term performance and recycling studies showed that the catalyst was robust and remained active even after six recycling experiments. EPR measurements were performed to deduce the reaction mechanism in the presence of POBN (α-(4-pyridyl-1-oxide)-N-tert-butylnitrone) as a spin-trapping agent, which confirmed the formation of CH2OH radicals and H radicals, wherein the solvent plays an active role in a nonconventional manner. A plausible mechanism was proposed for the oxidative esterification of alcohols on the basis of EPR findings. The presence of a cobalt core along with cobalt oxide and the electron-rich N-, O-, and S-doped carbon shell displayed synergistic effects to afford good to excellent yields of products.
- Nandan, Devaki,Zoppellaro, Giorgio,Med?ík, Ivo,Aparicio, Claudia,Kumar, Pawan,Petr, Martin,Tomanec, Ond?ej,Gawande, Manoj B.,Varma, Rajender S.,Zbo?il, Radek
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p. 3542 - 3556
(2018/08/07)
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- Pentafluoroperbenzoic acid as the efficient reagent for Baeyer–Villiger oxidation of cyclic ketones
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The Baeyer–Villiger oxidation of cyclic ketones with pentafluoroperbenzoic acid provides the corresponding lactones in 40–98% yields.
- Khusnutdinov, Ravil I.,Egorova, Tatyana M.,Aminov, Rishat I.,Dzhemilev, Usein M.
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p. 644 - 645
(2018/12/13)
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- Efficient Baeyer–Villiger Oxidation Catalysed by Silver Nanoparticles Stabilized on Modified Montmorillonite
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Abstract: Silver nanoparticles supported on modified montmorillonite clay (Ag-NPs@mont), were utilized as catalyst for the Baeyer–Villiger oxidation of various ketones with hydrogen peroxide as an oxidant under solvent free condition at room temperature. The modification of Montmorillonite K10 clay was carried out with HCl under controlled conditions for generating a high surface area porous matrix which acts as support for the in situ generation of Silver nanoparticles. The synthesized nanocomposite material was characterized by UV–Visible spectroscopy, powder XRD, SEM-EDX, TEM and N2 adsorption–desorption analysis. The catalyst can be recycled and reused several times without significant loss of their catalytic activity. Graphical Abstract: [Figure not available: see fulltext.].
- Borah, Subrat Jyoti,Das, Diganta Kumar
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p. 3669 - 3677
(2018/11/21)
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- Method for preparing lactone by ion-catalyzed intramolecular cyclization of diols
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The invention relates to a method for performing catalytic oxidative intramolecular cyclization of diols to obtain lactone under a mild condition by using metal iron salt as a catalyst and organic small molecular nitroxide free radicals as a cocatalyst. The method comprises the following steps: using aromatic diols and aliphatic diols with different substituents as substrates, using the metal iron salt as the catalyst, using the organic small molecular nitroxide free radicals as the cocatalyst, using air as an oxidant, and performing a catalytic oxidative reaction of the diols in a non-halogen solvent under the mild condition to obtain the lactone. A catalytic system adopted by the invention can overcome various defects of the conventional catalyst, and an iron catalyst system which is cheap, easy to obtain, non-toxic and high in activity is used; economical, safe and environment-friendly air is used as the oxidant; the reaction can be performed under a room temperature condition; the catalytic system has few components, and a ligand or an alkali compound is not required to be additionally added; the reaction has the advantages of easy operation, high catalytic efficiency, easy product separation and the like; the method has a very mild requirement on the reaction condition and has good research and application prospects.
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Paragraph 0036; 0037
(2017/08/29)
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- Preparation method of 2-diethylamino-1-methylethyl-7-cyclohexyl-7-oxoheptanoate
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The invention provides a compound 2-diethylamino-1-methylethyl-7-cyclohexyl-7-oxo-heptanoate (1) and a synthesis method thereof. The compound 1 adopts a structural formula as shown in the specification. The invention further provides the application of the compound 1 as an impurity reference substance for monitoring synthesis of an active pharmaceutical ingredient of rociverine. By taking cycloheptanone as a starting material, the compound 1 is synthesized through a four-step reaction; the obtained product is simple in posttreatment of each step, the product is convenient and easy to obtain, the compound 1 is suitable for being synthesized on a large scale, and a relevant substance or the impurity reference substance are provided for quality research on the synthesis of the active pharmaceutical ingredient of the rociverine.
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Paragraph 0022; 0050; 0051
(2017/11/04)
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- Efficient Baeyer-Villiger electro-oxidation of ketones with molecular oxygen using an activated carbon fiber electrode in ionic liquid [bmim][OTf]
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A new and efficient method for the synthesis of lactones and esters involving the application of an molecular oxygen-based electro-catalytic oxidation system and ionic liquid [bmim][OTf] as electrolyte has been developed. The reaction between various ketones with molecular oxygen proceeds in a three-electrode cell under constant current conditions in [bmim][OTf] at room temperature to give the corresponding esters and lactones in good to excellent isolated yield. Additionally, the possible mechanism of Baeyer-Villiger oxidation of ketones in the electro-catalytic system is proposed.
- Hu, Yu Lin,Xie, Yi Bi,Li, De Jiang
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p. 297 - 306
(2016/08/05)
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- Stabilized Fe3O4 magnetic nanoparticles into nanopores of modified montmorillonite clay: A highly efficient catalyst for the Baeyer-Villiger oxidation under solvent free conditions
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In situ generation of Fe3O4 magnetic nanoparticles (Fe3O4@AT-mont.) into the nanopores of modified montmorillonite (AT-mont.) clay has been carried out. Modification of the montmorillonite was done by acid (4 M HCl) activation under controlled conditions for generating nanopores, which act as a "host" for the Fe3O4 nanoparticles. The synthesized Fe3O4@AT-mont. was characterized by PXRD, TEM, SEM-EDX, XPS, VSM and surface area analysis. The average particle size of Fe3O4 nanoparticles was found to be around 10 nm and exhibit a face centered cubic (fcc) lattice geometry. Fe3O4@AT-mont. showed efficient catalytic activity for the Baeyer-Villiger oxidation of various cyclic and aromatic ketones in the presence of hydrogen peroxide as an oxidant at room temperature under solvent free conditions and exhibited conversion of up to 98%. The catalyst was magnetically recovered and recycled up to the third run without any significant loss of efficiency.
- Saikia, Pallab Kumar,Sarmah, Podma Pollov,Borah, Bibek Jyoti,Saikia, Lakshi,Saikia, Kokil,Dutta, Dipak Kumar
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p. 2843 - 2850
(2016/06/06)
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- Identification of Acyl Chain Oxidation Products upon Thermal Treatment of a Mixture of Phytosteryl/-stanyl Linoleates
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A mixture of phytosterols/-stanols, consisting of 75% β-sitosterol, 12% sitostanol, 10% campesterol, 2% campestanol, and 1% others, was esterified with linoleic acid. The resulting mixture of phytosteryl/-stanyl linoleates was subjected to thermal oxidation at 180 °C for 40 min. A silica solid-phase extraction was applied to separate a fraction containing the nonoxidized linoleates and nonpolar degradation products (heptanoates, octanoates) from polar oxidation products (oxo- and hydroxyalkanoates). In total, 15 sitosteryl, sitostanyl, and campesteryl esters, resulting from oxidation of the acyl chain, could be identified by GC-FID/MS. Synthetic routes were described for authentic reference compounds of phytosteryl/-stanyl 7-hydroxyheptanoates, 8-hydroxyoctanoates, 7-oxoheptanoates, 8-oxooctanoates, and 9-oxononanoates, which were characterized by GC-MS and two-dimensional NMR spectroscopy. The study provides data on the formation and identities of previously unreported classes of acyl chain oxidation products upon thermal treatment of phytosteryl/-stanyl fatty acid esters.
- Wocheslander, Stefan,Eisenreich, Wolfgang,Scholz, Birgit,Lander, Vera,Engel, Karl-Heinz
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p. 9214 - 9223
(2016/12/16)
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- One-pot conversion of cycloalkanes to lactones
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The one-pot conversion of cycloalkanes to their corresponding lactones was achieved through the use of a synthetic pathway consisting of a cytochrome P450 monooxygenase (CYP450) for initial oxyfunctionalization of the cycloalkane, an alcohol dehydrogenase for ketone production and a Baeyer-Villiger monooxygenase for lactone formation. Through variation of the cofactor dependence of the biocatalysts and the cofactor regeneration system, final product concentrations of nearly 3 g L-1 enantholactone (2-oxocanone) from cycloheptane was reached within 12 h with a total turnover number (TTN) of 4185 with respect to the CYP450.
- Pennec, Aliz,Hollmann, Frank,Smit, Martha S.,Opperman, Diederik J.
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p. 236 - 239
(2015/03/04)
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- Base-free oxidation of alcohols to esters at room temperature and atmospheric conditions using nanoscale Co-based catalysts
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The direct oxidation of alcohols to esters with molecular oxygen is an attractive and crucial process for the synthesis of fine chemicals. To date, the heterogeneous catalyst systems that have been identified are based on noble metals or have required the addition of base additives. Here, we show that Co nanoparticles embedded in nitrogen-doped graphite catalyze the aerobic oxidation of alcohols to esters at room temperature under base-free and atmospheric conditions. Our Co@C-N catalytic system features a broad substrate scope for aromatic and aliphatic alcohols as well as diols, giving their corresponding esters in good to excellent yields. This apparently environmentally benign process provides a new strategy with which to achieve selective oxidation of alcohols.
- Zhong, Wei,Liu, Hongli,Bai, Cuihua,Liao, Shijun,Li, Yingwei
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p. 1850 - 1856
(2015/03/14)
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- Fabrication of Ag/WO3 nanobars for Baeyer-Villiger oxidation using hydrogen peroxide
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We report the preparation of Ag/WO3 nanobars, mediated by cationic surfactant CTAB through hydrothermal route. XRD revealed the formation of metallic Ag supported on monoclinic WO3 phase and TEM diagram showed the formation of bar-like structure, where supported Ag nanoparticles are in the range between 2 and 7 nm. The catalyst exhibited high activity for selective oxidation of cyclohexanone to caprolactone with H2O2. A cyclohexanone conversion of 97% with 99% caprolactone selectivity was achieved over this catalyst at 80°C temperature. Moreover, the catalyst did not show any significant activity loss even after 5 reuses and proved its efficiency in the oxidation of other cycloalkanones also.
- Ghosh, Shilpi,Acharyya, Shankha Shubhra,Singh, Raghuvir,Gupta, Piyush,Bal, Rajaram
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- Efficient and convenient oxidation of aldehydes and ketones to carboxylic acids and esters with H2O2 catalyzed by Co4HP2Mo15V3O62 in ionic liquid [TEBSA][BF4]
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A simple, efficient, and eco-friendly procedure for the oxidation of aldehydes and ketones to carboxylic acids and esters with H2O2 catalyzed by Co4HP2Mo15V3O62 in ionic liquid [TEBSA][BF4] has been developed. This atom-economical protocol affords the target products in good to high yields. The products can be separated by a simple extraction with organic solvent, and the catalytic system can be recycled and reused without loss of catalytic activity. Additionally, the possible mechanism of oxidation in the catalytic system is proposed. This journal is
- Hu, Yu-Lin,Li, De-Jiang,Li, Dong-Sheng
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p. 24936 - 24943
(2015/03/30)
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- The dual role of micelles as templates and reducing agents for the fabrication of catalytically active hollow silver nanospheres
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We report a simple and efficient protocol for fabrication of colloidal hollow silver nanospheres of size less than 30 nm using an ABC triblock copolymer poly(styrene-b-vinyl-2-pyridine-b-ethylene oxide) in the absence of any reducing agents. The colloidal silver hollow nanoparticles serve as an efficient heterogeneous catalyst for Baeyer-Villiger oxidation of ketones to the corresponding lactones in the presence of anhydrous tert-butylhydroperoxide under liquid-phase conditions.
- Sasidharan, Manickam,Senthil, Chenrayan,Kumari, Vandana,Bhaumik, Asim
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supporting information
p. 733 - 736
(2015/02/19)
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- Chemo-enzymatic Baeyer-Villiger oxidation in the presence of Candida antarctica lipase B and ionic liquids
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A new method for the chemo-enzymatic Baeyer-Villiger oxidation of cyclic ketones to lactones has been developed. The influence of reaction parameters and the structure of various ionic liquids were studied. Free Candida antarctica lipase B or Novozyme-435 suspended in an ionic liquid was used as the catalytic phase. The reaction was carried out under mild conditions at room temperature using 30% aq. H2O2 as the oxidation agent. 1-Butyl-3-methyl bistriflimide was the most effective ionic liquid and increased the reaction rate compared to toluene. Lipase exhibited good stability, and the ionic liquid could be easily reused. Therefore, a general chemo-enzymatic method for the oxidation of cyclohexanones and cyclobutanones to obtain adequate lactones in high yields (79-95%) has been proposed.
- Drozdz, Agnieszka,Erfurt, Karol,Bielas, Rafal,Chrobok, Anna
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p. 1315 - 1321
(2015/02/19)
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- Broadening the scope of Baeyer-Villiger monooxygenase activities toward α,β-unsaturated ketones: A promising route to chiral enol-lactones and ene-lactones
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Three regiodivergent Baeyer-Villiger mono-oxygenases (enantioselectively) oxidized a series of cyclic α,β-unsaturated ketones into (chiral) either enol-lactones or ene-lactones. An easy-to-use and efficient biocatalytic process based on a host-microorganism deprived of unwanted activities (knock-out mutant) was developed to enable the exclusive synthesis of unsaturated lactones. This journal is the Partner Organisations 2014.
- Reignier,De Berardinis,Petit,Mariage,Hamze,Duquesne,Alphand
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supporting information
p. 7793 - 7796
(2014/07/08)
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- Synthesis of a series of hydroxycarboxylic acids as standards for oxidation of nonanoic acid
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The synthesis of a series of nonanoic acids hydroxylated in terminal,ω-1,ω-2,ω-3 positions is described. These compounds will be employed as useful standards for the study of enzymatic and microbiological oxidation of nonanoic acid.
- Rajabi, Mehdi,Lanfranchi, Moreno,Campo, Federica,Panza, Luigi
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supporting information
p. 1149 - 1154
(2014/04/03)
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- Total synthesis of the lipid mediator PD1n-3 DPA: Configurational assignments and anti-inflammatory and pro-resolving actions
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The polyunsaturated lipid mediator PD1n-3 DPA (5) was recently isolated from self-resolving inflammatory exudates of 5 and human macrophages. Herein, the first total synthesis of PD1n-3 DPA (5) is reported in 10 steps and 9% overall yield. These efforts, together with NMR data of its methyl ester 6, confirmed the structure of 5 to be (7Z,10R,11E,13E,15Z,17S,19Z)-10,17- dihydroxydocosa-7,11,13,15,19-pentaenoic acid. The proposed biosynthetic pathway, with the involvement of an epoxide intermediate, was supported by results from trapping experiments. In addition, LC-MS/MS data of the free acid 5, obtained from hydrolysis of the synthetic methyl ester 6, matched data for the endogenously produced biological material. The natural product PD1 n-3 DPA (5) demonstrated potent anti-inflammatory properties together with pro-resolving actions stimulating human macrophage phagocytosis and efferocytosis. These results contribute new knowledge on the n-3 DPA structure-function of the growing numbers of specialized pro-resolving lipid mediators and pathways.
- Aursnes, Marius,Tungen, J?rn E.,Vik, Anders,Colas, Romain,Cheng, Chien-Yee C.,Dalli, Jesmond,Serhan, Charles N.,Hansen, Trond V.
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supporting information
p. 910 - 916
(2014/05/20)
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- Functional divergence between closely related Baeyer-Villiger monooxygenases from Aspergillus flavus
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Baeyer-Villiger monooxygenases (BVMOs) catalyse the chemo-, regio- and enantioselective oxidation of ketones to esters and lactones. To date, most of the cloned BVMOs available are derived from bacteria, although Baeyer-Villiger oxidations using fungi have frequently been demonstrated. Here we report the cloning and characterization of four BVMOs from the fungus Aspergillus flavus NRRL3357. Phylogenetic analysis shows these four BVMOs to cluster in a distinct group apart from other well-characterized BVMOs including cyclohexanone, phenylacetone and 4-hydroxyacetophenone monooxygenase. Building on the Grogan classification/clustering of BVMOs, we have designated this new group of BVMOs, Group VI. Group VI BVMOs show an early divergence from the cyclopentanone monooxygenase (CPMO) type BVMOs (Group I). Substrate profiling using cyclic, bicyclic, aliphatic and aryl ketones show a clear divergence in function and specificity not only between this new group of BVMOs and the CPMO-type BVMOs, but also between the four A. flavus BVMO paralogues despite their high sequence similarity. This study not only contributes to the growing number of available BVMOs, but also addresses the current classification of Type I BVMOs, and the usefulness of phylogenetic clustering and prediction of function and selectivity when genome-mining is used to search for new biocatalysts.
- Ferroni,Smit,Opperman
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- Baeyer-villiger oxidation of cyclic ketones using aqueous hydrogen peroxide catalyzed by potassium salts of tungstophosphoric acid
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The salts of 12-tungstophosphoric acid catalysts are prepared with varying potassium content. The resulting catalysts are active for the Baeyer-Villiger oxidation of cyclic ketones with 30 wt% H2O2 and achieve good conversions and yields. KHPW is the preferred catalyst in the reaction because of its reusability and environmental benefits.
- Ma, Qingguo,Xing, Wanzhen,Xu, Junhui,Peng, Xinhua
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p. 941 - 943
(2014/06/23)
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- Direct room-temperature lactonisation of alcohols and ethers onto amides: An "amide strategy" for synthesis
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Last-minute deal: A direct lactonisation of ethers and alcohols onto amides that proceeds at room temperature under mild conditions is reported (see scheme). This allows the effective saving of up to two unproductive, sequential deprotection operations in synthetic sequences. Mechanistic studies are described, and a new "amide strategy" that exploits the dual robustness/late-stage selective activation properties of this functional group is outlined. Copyright
- Valerio, Viviana,Petkova, Desislava,Madelaine, Claire,Maulide, Nuno
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p. 2606 - 2610
(2013/03/14)
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- The steroid monooxygenase from Rhodococcus rhodochrous; A versatile biocatalyst
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The substrate scope of a steroid monooxygenase (STMO) from Rhodococcus rhodochrous DSM 43269 was investigated for a large range of different ketone substrates. These studies revealed that this enzyme not only oxygenates steroids, but also ketone moieties of a series of other open-chain ketones, such as cyclohexyl methyl ketone, cyclopentyl methyl ketone, and 3-acetylindole. Furthermore, the STMO catalyzed the oxygenation of cyclobutanone derivatives. Comparative biotransformations with recombinant Escherichia coli resting cells harboring the STMO, the cycloalkanone monooxygenase (CAMO) from Cylindrocarpon radicicola or the cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus revealed that the STMO is enantiodivergent compared to the CHMO-type. Moreover, the STMO resulted in a higher enantiomeric excess of the product lactones compared to the known BVMOs of the same enantiopreference, such as cyclopentanone monooxygenases.
- Leipold, Friedemann,Rudroff, Florian,Mihovilovic, Marko D.,Bornscheuer, Uwe T.
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p. 1620 - 1624
(2014/01/06)
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- The chemo-enzymatic Baeyer-Villiger oxidation of cyclic ketones with an efficient silica-supported lipase as a biocatalyst
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The synthesis and characterisation of new, silica-supported lipase biocatalysts and studies of their performance in Baeyer-Villiger oxidation (BVO) of cyclic ketones to lactones were described. Biocatalysts were obtained by immobilisation of Candida Antarctica lipase B onto siliceous materials with multimodal pore structure (MH) and also on typical SBA-15, chemically modified with organosilanes terminated with methyl, octyl and hexadecyl group. Biocatalysts structure was characterised by nitrogen adsorption and TEM/SEM imaging. The lipase presence was confirmed by FTIR spectroscopy, whereas protein loads were obtained from thermogravimetric data. They appeared to be notably larger for MH catalysts than SBA-15s and correlated with surface hydrophobicity of supports which decreased in the order Hd > Oc > Me, from 198 to 80 mg/g, for MH-Hd-L and MH-Me-L biocatalysts, respectively. Investigation of the biocatalysts performance (activity, stability, reusability) in BVO of cyclic ketones, using urea hydrogen peroxide as oxidant and ethyl acetate as both the peracid precursor and solvent, clearly demonstrated very large activity of MH biocatalysts. For the same lipase load activity decreased in the order MH-Me-L > MH-Oc-L > MH-Hd-L, with that of least active (MH-Hd-L) catalysts being even trice larger than of Novozyme-435 under equal mass basis. The biocatalysts showed good stability, even in the presence of 60% aq. hydrogen peroxide, and facile reuse. On this basis we proposed a general chemo-enzymatic BVO method for oxidation of cyclohexanones and cyclobutanone to obtain adequate lactones with high yields (80-98%).
- Drozdz,Chrobok,Baj,Szymańska,Mrowiec-Bia?on?,Jarz?bski
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p. 163 - 170
(2013/09/02)
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- Design, synthesis, and biological evaluation of N-Alkylated deoxynojirimycin (DNJ) derivatives for the treatment of dengue virus infection
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We recently described the discovery of oxygenated N-alkyl deoxynojirimycin (DNJ) derivative 7 (CM-10-18) with antiviral activity against dengue virus (DENV) infection both in vitro and in vivo. This imino sugar was promising but had an EC50 against DENV in BHK cells of 6.5 μM, which limited its use in in vivo. Compound 7 presented structural opportunities for activity relationship analysis, which we exploited and report here. These structure-activity relationship studies led to analogues 2h, 2l, 3j, 3l, 3v, and 4b-4c with nanomolar antiviral activity (EC50 = 0.3-0.5 μM) against DENV infection, while maintaining low cytotoxicity (CC50 > 500 μM, SI > 1000). In male Sprague-Dawley rats, compound 3l was well tolerated at a dose up to 200 mg/kg and displayed desirable PK profiles, with significantly improved bioavailability (F = 92 α 4%).
- Yu, Wenquan,Gill, Tina,Wang, Lijuan,Du, Yanming,Ye, Hong,Qu, Xiaowang,Guo, Ju-Tao,Cuconati, Andrea,Zhao, Kang,Block, Timothy M.,Xu, Xiaodong,Chang, Jinhong
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supporting information; experimental part
p. 6061 - 6075
(2012/08/14)
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- A mild and clean Baeyer-Villiger oxidation of ketones using sodium peroxydisulfate as oxidant catalyzed by silica-supported aluminum chloride
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Sodium peroxydisulfate was used as the oxidant for Baeyer-Villiger oxidation of a variety of cyclic and acyclic ketones at room temperature in the presence of Silica-supported aluminum chloride (silica-AlCl3) as catalyst. The catalyst was prepared by a simple procedure, which exhibited high catalytic activity for the Baeyer- Villiger oxidation of ketones using environmental friendly sodium peroxydisulfate as oxidizing agent. Iranian Chemical Society 2012.
- Mahmoodi, Nosrat Ollah,Heirati, Seyedeh Zahra Dalil,Ekhlasi-Kazaj, Kamel
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p. 521 - 528
(2013/02/22)
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- Aerobic lactonization of diols by biomimetic oxidation
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Coming up for air: Highly efficient aerobic lactonization can be carried out by a biomimetic oxidation system based on coupled redox catalysts (ruthenium catalyst and electron transfer mediators). This system leads to a low-energy electron transfer from diol to molecular oxygen. Various diols were aerobically oxidized to the corresponding five- to nine-membered lactones in good to high yields under mild reaction conditions (see scheme).
- Endo, Yoshinori,Baeckvall, Jan-E.
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supporting information; experimental part
p. 12596 - 12601
(2011/12/03)
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- A total synthesis of natural Rhizobialide
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Natural butanolide Rhizobialide was synthesized for the first time in enantiopure form with the stereogenic center derived from glutamic acid.
- Guan, Jing,Zou, Yang,Gao, Po,Wu, Yikang,Yue, Zhengyu
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scheme or table
p. 1613 - 1617
(2011/07/08)
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- Baeyer-Villiger oxidation of ketones in ionic liquids using molecular oxygen in the presence of benzaldehyde
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A new and efficient method for the synthesis of lactones involving the application of an oxygen/benzaldehyde system as the oxidant and ionic liquids as solvents is reported. A significant rate enhancement was observed at 90 °C when the oxidation of ketones was carried out in the presence of a free radical initiator. The oxidation of model cyclic ketones, such as cyclopentanone, cyclohexanone, 2-methylcyclohexanone, 2-norbornone, 2-adamantanone and cycloheptanone gave lactones in high yields (84-90%) within relatively short periods of time, with the possibility of effective ionic liquids recycling. Additionally, discussion of the free radical mechanism of this reaction is proposed.
- Chrobok, Anna
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experimental part
p. 2940 - 2943
(2010/06/17)
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- Synthesis of 2-normisoprostol, methyl6-(3-hydroxy-2-((E)-4-hydroxy-4- methyloct-1-enyl)-5-oxocyclopentyl)hexanoate
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Synthesis of 2-normisoprostol, methyl 6-(3-hydroxy-2-((E)-4-hydroxy-4- methyloct-1-enyl)-5-oxocyclopentyl)hexanoate (3), employing two-component coupling strategy based on 1,4-addition followed by DDQ-mediated triethyl silyl deprotection is reported. Desired key intermediates, methyl 6-(3-triethyl silyloxy-5-oxocyclopent-1-enyl)hexanoate (4) and (E)-1-(tributylstannyl)-4- methyloct-1-en-4-yloxy)triethylsilane (5), were prepared from commercially available cycloheptanone and propargyl bromide, and the intermediates were coupled to obtain 3 in a convergent approach.
- Harikrishna,Mohan, H. Rama,Dubey,Subbaraju, Gottumukkala V.
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experimental part
p. 2763 - 2775
(2009/12/06)
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- Baeyer-villiger oxidation of cycloalkanones with in situ generated hydrogen peroxide from alcohols and molecular oxygen using NHPI as a key catalyst
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One-pot Baeyer Villiger oxidation of cycloalkanones was successfully achieved by allowing them to react with hydrogen peroxide generated in situ from benzhydrol and molecular oxygen assisted by N-hydroxyphthalimide (NHPI) and 2,2-azobisisobutyronitrile (AIBN). This method provides an alternative synthetic route to lactones from cycloalkanones using sec-alcohols and molecular oxygen assisted by NHPI.
- Kamae, Kenichiro,Obora, Yasushi,Ishii, Yasutaka
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scheme or table
p. 891 - 895
(2009/12/25)
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- Baeyer-Villiger oxidation of ketones with a silica-supported peracid in supercritical carbon dioxide under flow conditions
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[2-Percarboxyethyl]-functionalized silica reacts with ketones in supercritical carbon dioxide at 250 bar and 40 °C under flow conditions to yield the corresponding esters and lactones. The solid reagent can be easily recycled through treatment with 70% hydrogen peroxide in the presence of an acid at 0°C. This procedure not only simplifies the isolation of the reaction products, but has the advantage of using only water and carbon dioxide as solvents under mild conditions.
- Mello, Rossella,Olmos, Andrea,Parra-Carbonell, Javier,Gonzalez-Nunez, Maria Elena,Asensio, Gregorio
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experimental part
p. 994 - 999
(2010/04/23)
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- Structure-activity relationship study of flowering-inducer FN against Lemna paucicostata
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FN1 (1) and FN2 (2), cycloadducts of α-ketol octadecadienoic acid (3) with norepinephrine (NE), induce flowering in Lemna paucicostata. In order to broaden our understanding of structural requirements of FN?for flower induction, nine analogs of 3 (4-12) were synthesized and reacted with NE under basic conditions. These analogs, except for 8, 10, and 12, exhibited significant activity regarding to floral induction in L. paucicostata. Similar experiments were carried out by using 3 and epinephrine, and it was demonstrated that these products also possessed biological activity.
- Kai, Kenji,Takeuchi, Jun,Kataoka, Taichi,Yokoyama, Mineyuki,Watanabe, Naoharu
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p. 6760 - 6769
(2008/12/21)
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- Switching from S- to R-selectivity in the Candida antarctica lipase B-catalyzed ring-opening of ω-methylated lactones: Tuning polymerizations by ring size
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Novozym 435-catalyzed ring-opening of a range of ω-methylated lactones demonstrates fascinating differences in rate of reaction and enantioselectivity. A switch from S- to R-selectivity was observed upon going from small (ring sizes ≤7) to large lactones (ring sizes ≥8). This was attributed to the transition from a cisoid to a transoid conformational preference of the ester bond on going from small to large lactones. The S-selectivity of the ring-opening of the small, cisoid lactones was low to moderate, while the R-selectivity of the ring-opening of the large transoid lactones was surprisingly high. The S-selectivity of the ring-opening of the small, cisoid lactones combined with the established R-selectivity of the transesterification of (aliphatic) secondary alcohols prevented polymerization from taking place. Ring-opening of the large, transoid lactones was R-selective with high enantioselectivity. As a result, these lactones could be polymerized, without exception, by straightforward kinetic resolution polymerization, yielding the enantiopure R-polyester with excellent enantiomeric excess (>99%).
- Van Buijtenen, Jeroen,Van As, Bart A. C.,Verbruggen, Marloes,Roumen, Luc,Vekemans, Jef A. J. M.,Pieterse, Koen,Hilbers, Peter A. J.,Hulshof, Lumbertus A.,Palmans, Anja R. A.,Meijer
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p. 7393 - 7398
(2008/02/08)
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- Baeyer-Villiger oxidation in supercritical CO2 with potassium peroxomonosulfate supported on acidic silica gel
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Supercritical carbon dioxide (scCO2) is an efficient reaction medium to perform the Baeyer-Villiger oxidation with hydrated silica-supported potassium peroxomonosulfate (h-SiO2·KHSO5) under flow-through conditions. Hydration modulates the reactivity of the active surface by softening the acidity of the KHSO4 present in the supported reagent. The reaction in scCO2 is much more efficient than in n-hexane under similar conditions, which is attributed to better transport and solvating properties of the supercritical medium with regard to n-hexane.
- Gonzalez-Nunez, Maria E.,Mello, Rossella,Olmos, Andrea,Asensio, Gregorio
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p. 6432 - 6436
(2007/10/03)
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