Ruthenium(II)‐Catalyzed Double Annulation of Quinones: Step‐Economical Access to Valuable Bioactive Compounds

Júnior, Eufrânio N. da Silva; Carvalho, Renato L. de; Almeida, Renata G.; Rosa, Luísa G.; Fantuzzi, Felipe; Rogge, Torben; Costa, Pedro Mikael da Silva; Pessoa, Cláudia; Jacob, Claus; Ackermann, Lutz

doi:10.1002/chem.202001434

Cited by 27 publications

(17 citation statements)

References 83 publications

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“…were prepared as described in the literature [90]. Para-quinones and derivatives 379, 380, 382, 414, 415, 465, 470, 477, were synthesized following the previously published studies in the literature [76,99]. Hydrazo derivatives 666, 668 and 673 were prepared according to previously published reports and their data are consistent with the literature [68].…”

Section: Synthesis Of Candidate Inhibitorsmentioning

confidence: 99%

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Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

Santos¹,

Kronenberger

Almeida

et al. 2022

Preprint

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The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In the present work, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC50) values between 0.41 μM and 66 μM. In addition, eight compounds inhibited PLpro with IC50 ranging from 1.7 μM to 46 μM. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.

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Section: Synthesis Of Candidate Inhibitorsmentioning

confidence: 99%

“…and pyrrolonaphthoquinones [73,76], in addition to other derivatives based on paraquinones [64,75]. The selected compounds for this group exhibit a broad substitution pattern but, in general, arylamino and aryl groups are often observed.…”

Section: Assembly Of a Chemical Library For Virtual Screening Against Mpromentioning

confidence: 99%

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

Santos¹,

Kronenberger

Almeida

et al. 2022

Preprint

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“… Ru‐catalysed two‐fold annulation of alkynes with 2‐acetamidonaphthoquinones [80] . a) An additional 5 mol % of the catalyst was added after 12 h. b) Without NaOPiv.…”

Section: Quinone Substrate‐directed C−h Metalationmentioning

confidence: 99%

“…Recently, our group associated with the Ackermann group have reported a two‐fold Ru‐catalysed annulation of 2‐acetamidonaphthoquinones with alkynes [80] . The first of these two annulation events involves C−H insertion into the quinonoid ring, directed by the acetamide group (Scheme 47).…”

Section: Quinone Substrate‐directed C−h Metalationmentioning

confidence: 99%

The Different Facets of Metal‐Catalyzed C−H Functionalization Involving Quinone Compounds

Wood

Carvalho

Júnior

2021

The Chemical Record

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Metal‐catalysed C−H functionalization has emerged as a powerful platform for the derivatization of quinones, a class of compounds with wide‐ranging applications. This review organises and discusses the evolution of this chemistry from early Fujiwara‐Moritani reactions, through to modern directing‐group assisted C−H functionalization processes, including C−H functionalization reactions directed by the quinone ring itself. Mechanistic details of these reactions are provided to afford insight into how the unique reactivity of quinoidal compounds has been leveraged in each example.

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“…[67] Then the same group developed ar uthenium(II)-catalyzed double CÀHa ctivation/annulation of quinones and alkynes for the construction of polycyclic quinoidal compounds in one step, which displayed potential antitumorb ioactivity (Scheme 38). [68] Many polycyclic products possessed very low isolated yields, whereas the yields of all compounds would be increased when an additional 5mol %R u II catalystw as added after 12 h.…”

Section: Ruthenium Catalysismentioning

confidence: 99%

Transition Metal‐Catalyzed Intermolecular Cascade C−H Activation/Annulation Processes for the Synthesis of Polycycles

Song

Eycken

2020

Chemistry A European J

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Polycycles are abundantly presenti nn umerous advanced chemicals, functional materials, bioactive molecules and natural products. However,t he strategies for the synthesis of polycycles are limited to classical reactions and transition metal-catalyzed cross-coupling reactions, requiring pre-functionalized starting materials and lengthy synthetic operations. The emergence of novel approaches shows great promise for the fields of organic/medicinal/materials chemistry.A mong them, transition metal-catalyzed CÀHa ctivation followed by intermolecular annulation reactions prevail, due to their straightforward manner with high atomand step-economy,p roviding rapid, concise and efficient methods for the construction of diverse polycycles. Several strategies have been developed for the synthesis of polycycles, relying on sequential multiple CÀHa ctivation/annulation, or combination of CÀHa ctivation/annulation and further interaction with ap roximal group, or merger of CÀHa ctivation with ac ycloaddition reaction, or in situ formation of the directing group. These are attractive, efficient, step-and atom-economic methods startingf rom commerciallya vailable materials. This Minireview will provide an introduction to transition metal-catalyzed CÀHa ctivation for the synthesis of polycycles, helping researchers to discoveri ndirect connections and reveal hiddeno pportunities. It will also promote the discoveryo fn ovel synthetic strategies relying on CÀHa ctivation.

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Ruthenium(II)‐Catalyzed Double Annulation of Quinones: Step‐Economical Access to Valuable Bioactive Compounds

Cited by 27 publications

References 83 publications

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

The Different Facets of Metal‐Catalyzed C−H Functionalization Involving Quinone Compounds

Transition Metal‐Catalyzed Intermolecular Cascade C−H Activation/Annulation Processes for the Synthesis of Polycycles

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