- A scalable electrochemical dehydrogenative cross-coupling of P(O)H compounds with RSH/ROH
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A practical, scalable electrochemical dehydrogenative cross-coupling of P(O)H compounds with thiols, phenols and alcohols in both an undivided cell and a continuous-flow setup is disclosed. Its broad substrate scope (>50 examples), good functional-group tolerance and scalability (>10 g) show potential for practical synthesis. A preliminary mechanistic study suggests that the phosphorus radicals are involved in the catalytic cycle.
- Li, Yujun,Yang, Qi,Yang, Liquan,Lei, Ning,Zheng, Ke
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supporting information
p. 4981 - 4984
(2019/05/21)
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- Cellular protection of SNAP-25 against botulinum neurotoxin/A: Inhibition of thioredoxin reductase through a suicide substrate mechanism
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Botulium neurotoxins (BoNTs) are among the most lethal toxins known to man. They are comprised of seven serotypes with BoNT/A being the most deadly; yet, there is no approved therapeutic for their intoxication or one that has even advanced to clinical trials. Botulinum neurotoxicity is ultimately governed through light chain (LC) protease SNARE protein cleavage leading to a loss of neurotransmitter release. Pharmacological attempts to ablate BoNT/A intoxication have sought to either nullify cellular toxin entry or critical biochemical junctions found within its intricate mechanism of action. In these regards, reports have surfaced of nonpeptidic small molecule inhibitors, but few have demonstrated efficacy in neutralizing cellular toxicity, a key prerequisite before rodent lethality studies can be initiated. On the basis of a lead discovered in our BoNT/A cellular assay campaign, we investigated a family of N-hydroxysuccinimide inhibitors grounded upon structure activity relationship (SAR) fundamentals. Molecules stemming from this SAR exercise were theorized to be protease inhibitors. However, this proposition was overturned on the basis of extensive kinetic analysis. Unexpectedly, inhibitor data pointed to thioredoxin reductase (TrxR), an essential component required for BoNT protease translocation. Also unforeseen was the inhibitors' mechanism of action against TrxR, which was found to be brokered through a suicide-mechanism utilizing quinone methide as the inactivating element. This new series of TrxR inhibitors provides an alternative means to negate the etiological agent responsible for BoNT intoxication, the LC protease.
- Seki, Hajime,Xue, Song,Pellett, Sabine,?ilhár, Peter,Johnson, Eric A.,Janda, Kim D.
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supporting information
p. 5568 - 5575
(2016/06/01)
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- The α-effect in nucleophilic substitution reactions of Y-substituted-phenyl diphenylphosphinates with HOO- and OH -
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Second-order rate constants (kHOO-) for the nucleophilic substitution reactions of Y-substituted-phenyl diphenylphosphinates (4a-4i) with HOO- in H2O have been measured spectrophotometrically. The a-nucleophile
- Hong, Hyo-Jeong,Bae, Ae Ri,Um, Ik-Hwan
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p. 2251 - 2255
(2013/09/24)
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- Kinetics and reaction mechanism for alkaline hydrolysis of Y-substituted-phenyl diphenylphosphinates
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The second-order rate constants (kOH-) for the reactions of Y-substituted-phenyl diphenylphosphinates (4a-4i) with OH- in H 2O at 25.0 ± 0.1 °C have been measured spectrophotometrically. Comparison of kOH- with kEtO- (the second-order rate constants for the corresponding reactions with E tO- in ethanol) has revealed that EtO- is less reactive than OH- although the former is ca. 3.4 pKa units more basic than the latter, indicating that the reactivity of these nucleophiles is not governed by their basicity alone. The Bronsted-type plot for the reactions of 4a-4i with OH- is linear with βlg = -0.36. The Hammett plot correlated with σ- constants results in a slightly better correlation than that correlated with σo constants but exhibits many scattered points. In contrast, the Yukawa-Tsuno plot for the same reactions exhibits an excellent linear correlation with ρ = 0.95 and r = 0.55. The r value of 0.55 implies that a negative charge develops partially on the O atom of the leaving group. Thus, the reactions of 4a-4i with OH- have been concluded to proceed through a concerted mechanism. Copyright
- Hong, Hyo-Jeong,Lee, Jieun,Bae, Ae Ri,Um, Ik-Hwan
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p. 2001 - 2005
(2013/09/02)
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- Aminolysis of Y-substituted phenyl diphenylphosphinates and benzoates: Effect of modification of electrophilic center from C=O to P=O
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(Chemical Equation Presented) The effect of modification of the electrophilic center from C=O to P=O on reactivity and reaction mechanism has been investigated for aminolysis of Y-substituted phenyl diphenylphosphinates (1a-j) and benzoates (2a-i). The phosphinates 1a-j are less reactive than the benzoates 2a-i. The reactions of 2,4-dinitrophenyl diphenylphosphinate (1a) with alicyclic secondary amines resulted in a linear Bronsted-type plot with a βnuc value of 0.38, while the corresponding reactions of 2,4-dinitrophenyl benzoate (2a) yielded a curved Bronsted-type plot. Similarly, a linear Bronsted-type plot with a β1g value of -0.66 was obtained for the reactions of 1a-j with piperidine, while the corresponding reactions of 2a-i gave a curved Bronsted-type plot. The linear Bronsted-type plots for the reactions of 1a-j have been taken as evidence for a concerted mechanism, while the curved Bronsted-type plots for the reactions of 2a-i have been suggested to indicate a change in the rate-determining step of a stepwise mechanism. The Hammett plot for the reactions of 1b-j exhibited a poor correlation with σ- constants (R2 = 0.962) but slightly better correlation with σo (R2 = 0.986). However, the Yukawa-Tsuno plot for the same reactions resulted in an excellent correlation (R2 = 0.9993) with an r value of 0.30. The aminolysis of 1a-j has been suggested to proceed through a concerted mechanism with an early transition state on the basis of the small βnuc and small r values.
- Um, Ik-Hwan,Shin, Young-Hee,Han, Jeong-Yoon,Mishima, Masaaki
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p. 7715 - 7720
(2007/10/03)
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- The Phenomenology of Differently Constructed Broensted-type Plots
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Two different methodologies for the construction of Broensted-type plots are compared; curved plots using the traditional approach and linear plots by a novel approach are obtained for the reaction of phenoxides with p-nitrophenyl diphenylphosphinate in dimethyl sulfoxide-water media at 25 deg C.
- Buncel, E.,Tarkka, R.,Hoz, S.
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p. 109 - 110
(2007/10/02)
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