- Exploring the scope of the 29G12 antibody catalyzed 1,3-dipolar cycloaddition reaction
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29G12 is a murine monoclonal antibody programmed to catalyze the regio- and enantioselective 1,3-dipolar cycloaddition reaction between 4-acetamidobenzonitrile N-oxide 1a and N,N-dimethylacrylamide 2a (Toker, J. D.; Wentworth, P., Jr.; Hu, Y.; Houk, K. N.; Janda, K. D. J. Am. Chem. Soc. 2000, 122, 3244). Given the unique nature of 29G12 as a protein biocatalyst for this chemical reaction, we have investigated both the substrate specificity and mechanistic parameters of the 29G12-catalyzed process. These studies have shown that while 29G12 is specific for its dipole substrate Ia, the antibody is highly promiscuous with respect to the dipolarophiles it can process. 29G12 accepts a bulky hydrophobic dipolarophile cosubstrate, with rates of product formation up to 70-fold faster than with the original substrate 2a. In all cases, the respective isoxazoline products are produced with exquisite regio- and stereochemical control (78-98% ee). Comparison between the steady-state kinetic parameters from the 29G12-catalyzed reaction of 1a with the most efficient versus the original dipolarophile cosubstrate (2m and 2a, respectively), reveals that while the effective molarities (EM)s are almost identical (EM (2m) 26 M; EM(2a) 23 M), the affinity of 29G12 for the larger dipolarophile 2m is more than 1 order of magnitude higher than for 2a [Km(2m) 0.44 ± 0.04 mM; Km(2a) 5.8 ± 0.4 mM]. Furthermore, when 2m is the cosubstrate, the affinity of 29G12 for its dipole 1a is also greatly improved [Km(1a) 0.82 ± 0.1 mM compared to Km(1a) 3.4 ± 0.4 mM when 2a is the cosubstrate]. An analysis of the temperature dependence of the 29G12-catalyzed reaction between 1a and 2m reveals that catalysis is achieved via a decrease in enthalpy of activation (ΔΔH? 4.4 kcal mol-1) and involves a large increase in the entropy of activation (ΔΔS? 10.4 eu). The improved affinity of 29G12 for the nitrile oxide Ia in the presence of 2m, coupled with the increase in ΔΔS? during the 29G12-catalyzed reaction between 1a and 2m supports the notion of a structural reorganization of the active site to facilitate this antibody-catalyzed reaction.
- Toker, Jonathan D.,Tremblay, Martin R.,Yli-Kauhaluoma, Jari,Wentworth, Anita D.,Zhou, Bin,Wentworth Jr., Paul,Janda, Kim D.
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- Enhanced Acrylate Production from 2-Acetoxypropanoic Acid Esters
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Reaction conditions and reactor geometry for producing acrylates in high yield from lactic acid-derived 2-acetoxypropanoic acid (APA) esters are presented. An acrylate ester yield of 75% is achieved from methyl and benzyl APA esters at 550 °C in a fixed bed reactor filled with nonporous silica particles, carbon dioxide as a diluent gas, and acetic acid as a co-feed with the APA ester. The yield from methyl and benzyl APA esters is remarkably higher than from ethyl or butyl esters of APA, which have hydrogen atoms on the β-carbon of the ester functional group and thus can undergo alkene elimination, leading to reduced acrylate yield. Under optimum conditions, APA conversion to acrylates is stable over 30 h of continuous operation with little carbon deposition on the contact material.
- Nezam, Iman,Peereboom, Lars,Miller, Dennis J.
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- Acid- And base-switched palladium-catalyzed γ-C(sp3)-H alkylation and alkenylation of neopentylamine
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The functionalization of remote unactivated C(sp3)-H and the reaction selectivity are among the core pursuits for transition-metal catalytic system development. Herein, we report Pd-catalyzed γ-C(sp3)-H-selective alkylation and alkenylation with removable 7-azaindole as a directing group. Acid and base were found to be the decisive regulators for the selective alkylation and alkenylation, respectively, on the same single substrate under otherwise the same reaction conditions. Various acrylates were compatible for the formation of C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds. The alkenylation protocol could be further extended to acrylates with natural product units and α,β-unsaturated ketones. The preliminary synthetic manipulation of the alkylation and alkenylation products demonstrates the potential of this strategy for structurally diverse aliphatic chain extension and functionalization. Mechanistic experimental studies showed that the acidic and basic catalytic transformations shared the same six-membered dimer palladacycle.
- Zhang, Jinquan,Zhang, Shuaizhong,Zou, Hongbin
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supporting information
p. 3466 - 3471
(2021/05/31)
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- Ouabain 19-site primary hydroxyl derivative as well as preparation method and application thereof
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The invention provides an ouabain 19-site primary hydroxyl derivative as well as a preparation method and application thereof. The structure of the ouabain 19-site primary hydroxyl derivative is shownas a formula I. The derivative has very low toxicity to normal cells and also has an excellent effect of inhibiting tumor cells. In addition, the derivative can effectively inhibit tumor cell migration and invasion. Therefore, the ouabain 19-site primary hydroxyl derivative has a very good application prospect in preparation of drugs for resisting tumors and inhibiting tumor invasion and/or migration.
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Paragraph 0063-0067
(2020/12/05)
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- BLOCK POLYMER, COSMETIC COMPOSITION COMPRISING IT AND COSMETIC TREATMENT PROCESS
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A block polymer containing, in a block with a Tg greater than 20° C., at least one monomer of formula (I): The invention also relates to a cosmetic composition comprising the block polymer in a cosmetically acceptable medium, and also to a cosmetic process for treating keratin materials using the composition, and most particularly to a process for making up the lips.
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- BLOCK POLYMER, COSMETIC COMPOSITION COMPRISING IT AND COSMETIC TREATMENT PROCESS
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A block polymer containing, in a block with a Tg of less than 20° C., at least one monomer of formula (I): The invention also relates to a cosmetic composition containing the block polymer in a cosmetically acceptable medium, and also to a cosmetic process for treating keratin materials using the composition, and most particularly to a process for making up the lips.
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- Asymmetric Diels-Alder reaction between acrylates and cyclopentadiene in the presence of chiral catalysts
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Asymmetric Diels-Alder reaction between cyclopentadiene and alkyl and cycloalkyl acrylates in the presence of new chiral catalysts, BBr 3?MentOEt, AlCl2OMent, BBr2OMent, and BBr(OMent)2, was studied. Optically active bicyclo[2.2.1]hept-2-ene- 5-carboxylates were synthesized. The influence of the reaction conditions on the total and optical yields and on the stereoselectivity of the adducts synthesized was examined. Nauka/Interperiodica 2006.
- Mamedov
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p. 1621 - 1625
(2008/02/07)
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- Nail varnish composition comprising at least one film-forming gradient copolymer and cosmetic process for making up and/or caring for the nails
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A nail varnish composition comprising, in a cosmetically acceptable medium, at least one film-forming gradient copolymer comprising at least two different monomeric units and exhibiting a mass polydispersity index (PI) of less than or equal to 2.5, the composition being capable of forming a film having an adhesion corresponding to a detachment percentage of less than 45%; a cosmetic process for making up and/or caring for the nails comprising the application to the nails of the cosmetic composition.
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- The 'Baylis - Hillman reaction' mechanism and applications revisited
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It is shown that reaction of aryl, benzyl, alkyl and functionalised alkyl acrylic esters with benzaldehyde, in the presence of 1,4-diazabicyclo[2.2.2] octane, strongly depends upon the electronic and steric effects of the ester part. This influence is also observed in condensation of furfuraldehyde. Moreover, for the first time, it is shown that the overall condensation is equilibrated.
- Fort, Yves,Berthe, Marie Christine,Caubere, Paul
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p. 6371 - 6384
(2007/10/02)
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