- Pd(II)-catalyzed asymmetric fluorination of α-aryl-α- cyanophosphonates with the aid of 2,6-lutidine
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We describe herein the catalytic asymmetric fluorination of α-cyanophosphonates using chiral Pd(H)-bisphosphine complexes. While metal complexes failed to promote the reaction alone, a reaction system involving Pd(II) and organic base such as 2,6-lutidine
- Moriya, Ken-Ichi,Hamashima, Yoshitaka,Sodeoka, Mikiko
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- Application of Dually Activated Michael Acceptor to the Rational Design of Reversible Covalent Inhibitor for Enterovirus 71 3C Protease
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Targeted covalent inhibitors (TCIs) have attracted growing attention from the pharmaceutical industry in recent decades because they have potential advantages in terms of efficacy, selectivity, and safety. TCIs have recently evolved into a new version with reversibility that can be systematically modulated. This feature may diminish the risk of haptenization and help optimize the drug-target residence time as needed. The enteroviral 3C protease (3Cpro) is a valuable therapeutic target, but the development of 3Cpro inhibitors is far from satisfactory. Therefore, we aimed to apply a reversible TCI approach to the design of novel 3Cpro inhibitors. The introduction of various substituents onto the α-carbon of classical Michael acceptors yielded inhibitors bearing several classes of warheads. Using steady-state kinetics and biomolecular mass spectrometry, we confirmed the mode of reversible covalent inhibition and elucidated the mechanism by which the potency and reversibility were affected by electronic and steric factors. This research produced several potent inhibitors with good selectivity and suitable reversibility; moreover, it validated the reversible TCI approach in the field of viral infection, suggesting broader applications in the design of reversible covalent inhibitors for other proteases.
- Ma, Yuying,Li, Linfeng,He, Shuai,Shang, Chengyou,Sun, Yang,Liu, Ning,Meek, Thomas D.,Wang, Yaxin,Shang, Luqing
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p. 6146 - 6162
(2019/07/08)
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- CYCLOLIC HYDRAZINE DERIVATIVES AS HIV ATTACHMENT INHIBITORS
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Compounds of Formula I are provided, including pharmaceutically acceptable salts thereof: wherein A is selected from the group consisting of: wherein Z is selected from the group consisting of: which are useful as HIV attachment inhibitors.
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Page/Page column 56
(2013/09/26)
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- Arylation of phosphoryl-stabilized carbanions with metal π-complexes of aryl chlorides and fluorides
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The nucleophilic aromatic substitution of halogen in metal arene π-complexes η6-(ArF)Cr(CO)3 and [η6-(ArHal)FeCp]+[PF6]- (Hal = F,Cl) with phosphoryl-stabilized carbanions ZCH2P(
- Artamkina, Galina A.,Sazonov, Petr K.,Beletskaya, Irina P.
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p. 4385 - 4387
(2007/10/03)
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- Carbanionic displacement reactions at phosphorus. Part III.1 Cyanomethylphosphonate vs. cyanomethylenediphosphonate. Synthesis and solid-state structures
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The results of the carbanionic reaction between acetonitrile and chlorophosphates depend strongly on the nature of the metallating agent (LiTMP, LDA, LiHMDS). According to the nature of the base, the reaction can be directed towards the formation of either cyanomethylphosphonates 3 or cyanomethylenediphosphonates 5. Electrophilic halogenation of lithiated cyanomethylphosphonate 2a leads to the mono-chloro 17, -bromo 18 and -iodo 19 derivatives. Only the monochloro product 17 is stable enough to be isolated in pure form. The structures of cyanobenzylphosphonate 10b, cyanomethylenediphosphonate 5b and its corresponding lithiated carbanion 4b are determined by X-ray crystallography. The polymeric structure, coupled with a wide charge delocalization, without C-Li contacts, is in agreement with the lack of reactivity towards electrophiles. The Royal Society of Chemistry 2000.
- Lorga, Bogdan,Ricard, Louis,Savignac, Philippe
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p. 3311 - 3316
(2007/10/03)
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- Copper(I) Salt-Mediated Arylation of Phosphinyl-Stabilized Carbanions and Synthetic Application to Heterocyclic Compounds
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The copper-mediated reaction of phosphinyl-stabilized carbanions 2a-c with aryl halides 1a-i in DMF or HMPA produced (arylmethyl)phosphonates 3-11 in good yields.Similar treatment of N-(2-iodophenyl)- and N-(2-iodophenyl)-N-methyl-α-(diethoxyphosphinyl)ac
- Minami, Toru,Isonaka, Takeshi,Okada, Yoshiharu,Ichikawa, Junji
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p. 7009 - 7015
(2007/10/02)
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- A NEW FACILE SYNTHESIS OF DIETHYL 1-ARYL-1-CYANOMETHANEPHOSPHONATES
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Titanium(IV) chloride-cytalyzed addition of diethyl trimethylsilyl phosphite to β-nitrostyrenes affords α-phosphoryl nitronates which, on treatment with low valent titanium in situ generated from titanium(IV) and zinc, are smoothly converted to 1-aryl-1-cyanomethanephosphonates in good yields.
- Kim, Dae Young,Oh, Dong Young
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p. 953 - 958
(2007/10/02)
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