Photocycloaddition of Phthalimide Anion to Alkenes − A Highly Efficient, Convergent Method for [2]Benzazepine Synthesis

Suau, Rafael; Sánchez-Sánchez, Cristóbal; Garcı́a-Segura, Rafael; Pérez‐Inestrosa, Ezequiel

doi:10.1002/1099-0690(200206)2002:12<1903::aid-ejoc1903>3.0.co;2-p

Cited by 13 publications

(24 citation statements)

References 21 publications

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“…Using the methodology developed in the Suau lab, 32 we were able to produce the benzoazepinediones 26 , 27 , 29 , and 30 in low but consistent yields from various vinyl aryl derivatives ( Scheme 4 and Table 2 ). The ketones in 26 , 27 , 29 , and 30 were reduced with NaBH 4 , to generate the corresponding alcohols 5 , 28 , 6 , and 31 as racemic mixtures ( Table 2 ).…”

Section: Results and Discussionmentioning

confidence: 99%

“…Following a procedure from Suau et al, 32 to a Pyrex Erlenmeyer flask containing 140 mL of ACN with 25 mL of H 2 O, were added phthalimide (1 g, 6.8 mmol) and NaOH (1 M, 2 mL). The reaction vessel was capped with a rubber septum, and styrene or substituted styrene derivative (2 equiv) was added and the reaction mixture was degassed using a stream of N 2 .…”

Section: Methodsmentioning

confidence: 99%

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Combination of Selective PARP3 and PARP16 Inhibitory Analogues of Latonduine A Corrects F508del-CFTR Trafficking

Centko¹,

Carlile

Barne³

et al. 2020

ACS Omega

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The marine natural product latonduine A ( 1 ) shows F508del-cystic fibrosis transmembrane regulator (CFTR) corrector activity in cell-based assays. Pull-down experiments, enzyme inhibition assays, and siRNA knockdown experiments suggest that the F508del-CFTR corrector activities of latonduine A and a synthetic analogue MCG315 ( 4 ) result from simultaneous inhibition of PARP3 and PARP16. A library of synthetic latonduine A analogs has been prepared in an attempt to separate the PARP3 and PARP16 inhibitory properties of latonduine A with the goal of discovering selective small-molecule PARP3 and PARP16 inhibitory cell biology tools that could confirm the proposed dual-target F508del-CFTR corrector mechanism of action. The structure activity relationship (SAR) study reported herein has resulted in the discovery of the modestly potent (IC 50 3.1 μM) PARP3 selective inhibitor (±)-5-hydroxy-4-phenyl-2,3,4,5-tetrahydro-1 H -benzo[ c ]azepin-1-one ( 5 ) that shows 96-fold greater potency for inhibition of PARP3 compared with its inhibition of PARP16 in vitro and the potent (IC 50 0.362 μM) PARP16 selective inhibitor (±)-7,8-dichloro-5-hydroxy-4-(pyridin-2-yl)-2,3,4,5-tetrahydro-1 H -benzo[ c ]azepin-1-one ( 6 ) that shows 205-fold selectivity for PARP16 compared with PARP3 in vitro . At 1 or 10 μM, neither 5 or 6 alone showed F508del-CFTR corrector activity, but when added together at 1 or 10 μM each, the combination exhibited F508del-CFTR corrector activity identical to 1 or 10 μM latonduine A ( 1 ), respectively, supporting its novel dual PARP target mechanism of action. Latonduine A ( 1 ) showed additive in vitro corrector activity in combination with the clinically approved corrector VX809, making it a potential new partner for cystic fibrosis combination drug therapies.

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Section: Results and Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Combination of Selective PARP3 and PARP16 Inhibitory Analogues of Latonduine A Corrects F508del-CFTR Trafficking

Centko¹,

Carlile

Barne³

et al. 2020

ACS Omega

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“…Thus, at [NaOH] » [PHT‐H], phthalimide anion absorbs light (Pyrex filter) and undergoes regioselective [2+2] photocycloaddition to unactivated alkenes to give [2]benzazepinediones (11). Under these conditions, no reaction or quenching of the fluorescence is observed upon excitation of phthalimide anion in the presence of phenylethyne or 1‐hexyne.…”

Section: Resultsmentioning

confidence: 99%

Photoinduced Addition of Phthalimide to Unactivated Alkynes†

Nájera

Garcı́a-Segura

Pérez‐Inestrosa

et al. 2006

Photochem Photobiol

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Photoexcited phthalimide in equilibrium with its conjugated base produces the regioselective hydrophthalimidation of conjugated alkynes. The vinylphthalimide thus obtained is hydrolyzed to the corresponding carbonyl compound. With unconjugated alkynes, the outcome is a double addition of phthalimide to the triple bond. The reaction is assumed to take place via single electron transfer from either the alkyne or the phthalimide anion to the excited phthalimide as the primary photoprocess.

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“…Suau und Mitarbeiter [123] konnten dieses Problem elegant umgehen, indem sie die abgeschwächte Oxidationskraft des anionischen Natriumphthalimids 64 − ausnutzten. Dadurch konnten effiziente und regiokontrollierte Photocyloadditionen mit erweiterter Substratbreite hinsichtlich der eingesetzten Alkene durchgeführt werden (Schema 37).…”

Section: Angeregte Anionische Verbindungen Als Reagenzienunclassified

Photoangeregte Anionen in organischen Reaktionen

2020

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Die Durchführung chemischer Reaktionen mit Licht erlaubt es, die eingestrahlte Energie selektiv auf bestimmte Moleküle zu fokussieren. Viele Reaktionen, an denen elektronisch angeregte Spezies beteiligt sind, verlaufen über radikalische Zwischenstufen, die neue, einzigartige Reaktionswege ermöglichen und somit bekannte Syntheserouten zur Umwandlung organischer Moleküle erweitern. Der direkte Einsatz nicht funktionalisierter bzw. reaktionsträger Verbindungen ist ein erstrebenswertes Ziel, um chemische Prozesse nachhaltiger und atomökonomischer gestalten zu können. Es wurde gezeigt, dass angeregte Anionen mit gepaarten Elektronen enorme Potentiale in Elektronentransferreaktionen überwinden können und dass häufig ungewöhnliche Reaktivitäten im angeregten Zustand beobachtbar sind. In diesem Aufsatz fassen wir kurz die Eigenschaften der anionischen Photochemie zusammen, heben die wegweisenden Arbeiten auf diesem Gebiet hervor und diskutieren aktuelle Entwicklungen, die durch photoangeregte anionische Spezies in der organischen Synthese erzielt wurden.

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Photocycloaddition of Phthalimide Anion to Alkenes − A Highly Efficient, Convergent Method for [2]Benzazepine Synthesis

Cited by 13 publications

References 21 publications

Combination of Selective PARP3 and PARP16 Inhibitory Analogues of Latonduine A Corrects F508del-CFTR Trafficking

Combination of Selective PARP3 and PARP16 Inhibitory Analogues of Latonduine A Corrects F508del-CFTR Trafficking

Photoinduced Addition of Phthalimide to Unactivated Alkynes†

Photoangeregte Anionen in organischen Reaktionen

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