Substituent effects on axial chirality in 1-aryl-3,4-dihydroisoquinolines: controlling the rate of bond rotation

Roselló, Josep Mas; Staniland, Samantha; Turner, Nicholas J.; Clayden, Jonathan

doi:10.1016/j.tet.2016.01.037

Cited by 5 publications

(2 citation statements)

References 53 publications

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“…The product was washed with 1 N HCl (50 mL) and a saturated solution of sodium bicarbonate (50 mL) and dried with MgSO 4 . The organic layer was removed in vacuo to afford the known compound 8 61 (2.6 g, quantitative yield) as a yellow solid: 1 H NMR (400 MHz, CD 3 OD, Figure S7) δ 7.86 (d, J = 8.0 Hz, 1H), 7.38 (app. tt, J = 8.0, 1.2 Hz, 1H), 7.32−7.24 (m, 4H), 7.24−7.16 (m, 2H), 7.20−6.80 (m, 1H), 3.56 (t, J = 8.0 Hz, 2H), 2.92 (t, J = 7.6 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 , Figure S8) δ 169.6, 142.4, 140.0, 138.8, 131.2, 129.0, 128.9, 128.…”

Section: ■ Methodsmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa Alginate Synthesis by Ebselen Oxide and Its Analogues

et al. 2021

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Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that is frequently found in the airways of cystic fibrosis (CF) patients due to the dehydrated mucus that collapses the underlying cilia and prevents mucociliary clearance. During this life-long chronic infection, P. aeruginosa cell accumulates mutations that lead to inactivation of the mucA gene that results in the constitutive expression of algD-algA operon and the production of alginate exopolysaccharide. The viscous alginate polysaccharide further occludes the airways of CF patients and serves as a protective matrix to shield P. aeruginosa from host immune cells and antibiotic therapy. Development of inhibitors of alginate production by P. aeruginosa would reduce the negative impact from this viscous polysaccharide. In addition to transcriptional regulation, alginate biosynthesis requires allosteric activation by bis (3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) binding to an Alg44 protein. Previously, we found that ebselen (Eb) and ebselen oxide (EbO) inhibited diguanylate cyclase from synthesizing c-di-GMP. In this study, we show that EbO, Eb, ebsulfur (EbS), and their analogues inhibit alginate production. Eb and EbS can covalently modify the cysteine 98 (C98) residue of Alg44 and prevent its ability to bind c-di-GMP. However, P. aeruginosa with Alg44 C98 substituted with alanine or serine was still inhibited for alginate production by Eb and EbS. Our results indicate that EbO, Eb, and EbS are lead compounds for reducing alginate production by P. aeruginosa. Future development of these inhibitors could provide a potential treatment for CF patients infected with mucoid P. aeruginosa.

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Section: ■ Methodsmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa Alginate Synthesis by Ebselen Oxide and Its Analogues

et al. 2021

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“…Hence, the bis-phosphonylation could not be realized, and a “bypass” procedure had to be developed for the preparation of bisphosphines: after the mono-phosphonylation, the resulting phosphine oxide was reduced with a silane and then the second cross-coupling took place [ 100 - 103 ]. Heterocyclic analogs of BINAP as potential catalysts of new enantioselective approaches, such as biaryl isoquinolines (called Quinazolinaps) [ 104 , 105 ], 1-aryl-3,4-dihydroisoquinolines (DHIQs) [ 106 ] and a new class of naphthyl-indole heterobiaryl skeletons [ 107 ] were also developed.…”

Section: The Traditional Hirao Reactionmentioning

confidence: 99%

New Developments on the Hirao Reactions, Especially from “Green” Point of View

Henyecz

Keglevich

2019

COS

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Background: The Hirao reaction discovered ca. 35 years ago is an important P–C coupling protocol between dialkyl phosphites and aryl halides in the presence of Pd(PPh3)4 as the catalyst and a base to provide aryl phosphonates. Then, the reaction was extended to other Preagents, such as secondary phosphine oxides and H-phosphinates and to other aryl and hetaryl derivatives to afford also phosphinic esters and tertiary phosphine oxides. Instead of the Pd(PPh3)4 catalyst, Pd(OAc)2 and Ni-salts were also applied as catalyst precursors together with a number of mono- and bidentate P-ligands. Objective: In our review, we undertook to summarize the target reaction with a special stress on the developments attained in the last 6 years, hence this paper is an update of our earlier reviews in a similar topic. Conclusion: “Greener” syntheses aimed at utilizing phase transfer catalytic and microwave-assisted approaches, even under “P-ligand-free. or even solvent-free conditions are the up-to date versions of the classical Hirao reaction. The mechanism of the reaction is also in the focus these days.

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Stable C–N axial chirality in 1-aryluracil scaffold and differences in in vitro metabolic clearance between atropisomers of PDE4 inhibitor

Hasegawa

Kawamura

Tsuchikawa

et al. 2017

Bioorganic & Medicinal Chemistry

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Substituent effects on axial chirality in 1-aryl-3,4-dihydroisoquinolines: controlling the rate of bond rotation

Cited by 5 publications

References 53 publications

Inhibition of Pseudomonas aeruginosa Alginate Synthesis by Ebselen Oxide and Its Analogues

Inhibition of Pseudomonas aeruginosa Alginate Synthesis by Ebselen Oxide and Its Analogues

New Developments on the Hirao Reactions, Especially from “Green” Point of View

Stable C–N axial chirality in 1-aryluracil scaffold and differences in in vitro metabolic clearance between atropisomers of PDE4 inhibitor

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