- A general palladium-catalyzed cross-coupling of aryl fluorides and organotitanium (IV) reagents
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Pd(OAc)2/1-[2-(di-tert-butylphosphanyl)phenyl]-4-methoxy-piperidine was demonstrated to effectively catalyze cross-coupling of aryl fluoride and aryl(alkyl) titanium reagent. Both electron-deficient and electron-rich aryl fluoride can react effectively with nucleophile and provide extensive functional groups tolerance. 2-Arylated product was realized by selective activation of the C–F bond. Graphic abstract: [Figure not available: see fulltext.].
- He, Xiao-Yun
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p. 823 - 832
(2021/07/19)
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- A focused fragment library targeting the antibiotic resistance enzyme - Oxacillinase-48: Synthesis, structural evaluation and inhibitor design
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β-Lactam antibiotics are of utmost importance when treating bacterial infections in the medical community. However, currently their utility is threatened by the emergence and spread of β-lactam resistance. The most prevalent resistance mechanism to β-lactam antibiotics is expression of β-lactamase enzymes. One way to overcome resistance caused by β-lactamases, is the development of β-lactamase inhibitors and today several β-lactamase inhibitors e.g. avibactam, are approved in the clinic. Our focus is the oxacillinase-48 (OXA-48), an enzyme reported to spread rapidly across the world and commonly identified in Escherichia coli and Klebsiella pneumoniae. To guide inhibitor design, we used diversely substituted 3-aryl and 3-heteroaryl benzoic acids to probe the active site of OXA-48 for useful enzyme-inhibitor interactions. In the presented study, a focused fragment library containing 49 3-substituted benzoic acid derivatives were synthesised and biochemically characterized. Based on crystallographic data from 33 fragment-enzyme complexes, the fragments could be classified into R1 or R2 binders by their overall binding conformation in relation to the binding of the R1 and R2 side groups of imipenem. Moreover, binding interactions attractive for future inhibitor design were found and their usefulness explored by the rational design and evaluation of merged inhibitors from orthogonally binding fragments. The best inhibitors among the resulting 3,5-disubstituted benzoic acids showed inhibitory potential in the low micromolar range (IC50 = 2.9 μM). For these inhibitors, the complex X-ray structures revealed non-covalent binding to Arg250, Arg214 and Tyr211 in the active site and the interactions observed with the mono-substituted fragments were also identified in the merged structures.
- Akhter, Sundus,Lund, Bjarte Aarmo,Ismael, Aya,Langer, Manuel,Isaksson, Johan,Christopeit, Tony,Leiros, Hanna-Kirsti S.,Bayer, Annette
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supporting information
p. 634 - 648
(2018/01/19)
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- The 1,3-diaminobenzene-derived aminophosphine palladium pincer complex {C6H3[NHP(piperidinyl)2]2Pd(Cl)} - A highly active Suzuki-Miyaura catalyst with excellent functional group tolerance
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The rapidly prepared 1,3-diaminobenzenederived aminophosphine pincer complex {C6H3 [NHP(piperidinyl)2] 2Pd(Cl)} (1) is an effective Suzuki catalyst with excellent functional group tolerance. Side-product formations, such as homocoupling, debromation or protodeboration have only rarely been detected and if so, were in all cases below the 5% level. The presented reaction protocol is universally applicable. Experimental observations indicate that palladium nanoparticles are the catalytically active form of 1.
- Bolliger, Jeanne L.,Frech, Christian M.
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experimental part
p. 1075 - 1080
(2010/06/17)
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- An improved protocol for ligandless Suzuki-Miyaura coupling in water
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Using a reverse order of addition of reagents, PdCl2 and Pd(OAc)2 are efficient catalysts for the Suzuki-Miyaura reactions in water. The ligandless and mild conditions, the high stability of the catalytic system, short reaction time and good to excellent yields are important features of this protocol.
- Korolev, Dmitrii N.,Bumagin, Nikolay A.
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p. 4225 - 4229
(2007/10/03)
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