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1.
Green Chem ; 24(9): 3697-3703, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35694222

RESUMO

Natural allocolchicine and analogues derived thereof a tricyclic 6-7-6-system have been found as key scaffold of various biologically relevant molecules. However, the direct preparation of the allocolchicine motif remains difficult to date. Herein, we report on an electrooxidative radical cyclization of biarylynones with various carbon- and heteroatom-centered radical precursors via a sequential radical addition/7-endo-trig/radical cyclization domino reaction. This approach provides a step-economical and strategically novel disconnection for the facile assembly of a wide range of carbocyclic 6-7-6 fused ring systems. Remarkably, the sulfonyl group on the products could be easily removed by photocatalysis at room temperature with high yields.

2.
Angew Chem Int Ed Engl ; : e202205562, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35527721

RESUMO

Distal C(sp2 )-H and C(sp3 )-H functionalizations have recently emerged as step-economical tools for molecular synthesis. However, while the C(sp2 )-C(sp3 ) construction is of fundamental importance, its formation through double remote C(sp2 )-H/C(sp3 )-H activation has proven elusive. By merging the ruthenium-catalyzed meta-C(sp2 )-H functionalization with an aliphatic hydrogen atom transfer (HAT) process, we, herein, describe the catalyzed twofold remote C(sp2 )-H/C(sp3 )-H functionalizations via photo-induced ruthenium-mediated radical relay. Thus, meta-C(sp2 )-H arene bonds and remote C(sp3 )-H alkane bonds were activated by a single catalyst in a single operation. This process was accomplished at room temperature by visible light-notably without exogenous photocatalysts. Experimental and computational theory studies uncovered a manifold comprising ortho-C-H activation, single-electron-transfer (SET), 1,n-HAT (n=5-7) and σ-activation by means of a single ruthenium(II) catalyst.

3.
Nat Commun ; 13(1): 2588, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546155

RESUMO

Disulfides are widely found in natural products and find a wide range of applications in life sciences, materials chemistry and other fields. The preparation of disulfides mainly rely on oxidative couplings of two sulfur containing compounds. This strategy has many side reactions and other shortcomings. Herein, we describe the reductive nickel-catalyzed cross-electrophile coupling of unactivated alkyl bromides with symmetrical alkyl- and aryltetrasulfides to form alkyl-alkyl and aryl-alkyl unsymmetrical disulfides. This approach for disulfide synthesis is practical, relies on easily available, unfunctionalized substrates, and is scalable. We investigated the mechanism of this transformation and found that the tetrasulfide compound does not selectively break the central S-S bond, but regio-selectively generates trisulfide intermediates.


Assuntos
Dissulfetos , Níquel , Brometos , Catálise , Níquel/química
4.
Chemistry ; 28(37): e202200811, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35420234

RESUMO

A robust method for the selective labeling of peptides via manganese(I) catalysis was devised to achieve the C-2 alkenylation of tryptophan containing peptides with 1-ethynyl-o-carboranes. The manganese-catalyzed C-H activation was accomplished with high catalytic efficiency, and featured low toxicity, high functional group tolerance and excellent E-stereoselectivity. This approach unravels a promising tool for the assembly of o-carborane with structurally complex peptides of relevance to applications in boron neutron capture therapy.

5.
Chem Sci ; 13(12): 3461-3467, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35432858

RESUMO

Ruthenaelectro(ii/iv)-catalyzed intermolecular C-H acyloxylations of phenols have been developed by guidance of experimental, CV and computational insights. The use of electricity bypassed the need for stoichiometric chemical oxidants. The sustainable electrocatalysis strategy was characterized by ample scope, and its unique robustness enabled the late-stage C-H diversification of tyrosine-derived peptides.

6.
Chem Sci ; 13(14): 4088-4094, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35440980

RESUMO

Thioethers allowed for highly atroposelective C-H olefinations by a palladium/chiral phosphoric acid catalytic system under ambient air. Both N-C and C-C axial chiral (hetero)biaryls were successfully constructed, leading to a broad range of axially chiral N-aryl indoles and biaryls with excellent enantioselectivities up to 99% ee. Experimental and computational studies were conducted to unravel the walking mode for the atroposelective C-H olefination. A plausible chiral induction model for the enantioselectivity-determining step was established by detailed DFT calculations.

7.
Chemistry ; 28(29): e202200625, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35322915

RESUMO

A Ni-catalyzed Csp2 -OMe ortho-functionalization methodology to form chemoselectively alkyne monoannulation or aromatic homologation products is reported as a novel protocol towards the valorisation of substrates containing Csp2 -OMe units. Double activation of Csp2 -OMe and Csp2 -F bonds is also demonstrated. Further use of aromatic homologation products towards the synthesis of nanographene-like compounds is described.

8.
Chem Sci ; 13(9): 2729-2734, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35340853

RESUMO

Enantioselective electrocatalyzed transformations represent a major challenge. We herein achieved atropoenantioselective pallada-electrocatalyzed C-H olefinations and C-H allylations with high efficacy and enantioselectivity under exceedingly mild reaction conditions. With (S)-5-oxoproline as the chiral ligand, activated and non-activated olefins were suitable substrates for the electro-C-H activations. Dual catalysis was devised in terms of electro-C-H olefination, along with catalytic hydrogenation. Challenging enantiomerically-enriched chiral anilide scaffolds were thereby obtained with high levels of enantio-control in the absence of toxic and cost-intensive silver salts. The resource-economy of the transformation was even improved by directly employing renewable solar energy.

9.
Chem Sci ; 13(9): 2783-2788, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35340855

RESUMO

Despite indisputable progress in the development of electrochemical transformations, electrocatalytic annulations for the synthesis of biologically relevant three-dimensional spirocyclic compounds has as of yet not been accomplished. In sharp contrast, herein, we describe the palladaelectro-catalyzed C-H activation/[3 + 2] spiroannulation of alkynes by 1-aryl-2-naphthols. Likewise, a cationic rhodium(iii) catalyst was shown to enable electrooxidative [3 + 2] spiroannulations via formal C(sp3)-H activations. The versatile spiroannulations featured a broad substrate scope, employing electricity as a green oxidant in lieu of stoichiometric chemical oxidants under mild conditions. An array of spirocyclic enones and diverse spiropyrazolones, bearing all-carbon quaternary stereogenic centers were thereby accessed in a user-friendly undivided cell setup, with molecular hydrogen as the sole byproduct.

10.
ChemMedChem ; 17(9): e202200005, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35187791

RESUMO

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause life-threatening diseases in millions of people worldwide, in particular, in patients with cancer, and there is an urgent need for antiviral agents against this infection. While in vitro activities of artemisinins against SARS-CoV-2 and cancer have recently been demonstrated, no study of artemisinin and/or synthetic peroxide-based hybrid compounds active against both cancer and SARS-CoV-2 has been reported yet. However, the hybrid drug's properties (e. g., activity and/or selectivity) can be improved compared to its parent compounds and effective new agents can be obtained by modification/hybridization of existing drugs or bioactive natural products. In this study, a series of new artesunic acid and synthetic peroxide based new hybrids were synthesized and analyzed in vitro for the first time for their inhibitory activity against SARS-CoV-2 and leukemia cell lines. Several artesunic acid-derived hybrids exerted a similar or stronger potency against K562 leukemia cells (81-83 % inhibition values) than the reference drug doxorubicin (78 % inhibition value) and they were also more efficient than their parent compounds artesunic acid (49.2 % inhibition value) and quinoline derivative (5.5 % inhibition value). Interestingly, the same artesunic acid-quinoline hybrids also show inhibitory activity against SARS-CoV-2 in vitro (EC50 13-19 µm) and no cytotoxic effects on Vero E6 cells (CC50 up to 110 µM). These results provide a valuable basis for design of further artemisinin-derived hybrids to treat both cancer and SARS-CoV-2 infections.


Assuntos
Artemisininas , COVID-19 , Leucemia , Neoplasias , Quinolinas , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Artemisininas/farmacologia , COVID-19/tratamento farmacológico , Chlorocebus aethiops , Humanos , Leucemia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Peróxidos , Quinolinas/uso terapêutico , SARS-CoV-2 , Células Vero
11.
Angew Chem Int Ed Engl ; 61(20): e202200323, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35148009

RESUMO

Carboranes are boron-carbon molecular clusters that possess unique properties, such as their icosahedron geometry, high boron content, and delocalized three-dimensional aromaticity. These features render carboranes valuable building blocks for applications in supramolecular design, nanomaterials, optoelectronics, organometallic coordination chemistry, and as boron neutron capture therapy (BNCT) agents. Despite tremendous progress in this field, stoichiometric chemical redox reagents are largely required for the oxidative activation of carborane cages. In this context, electrosyntheses represent an alternative strategy for more sustainable molecular syntheses. It is only in recent few years that considerable progress has been made in electrochemical cage functionalization of carboranes, which are summarized in this Minireview. We anticipate that electrocatalysis will serve as an increasingly powerful stimulus within the current renaissance of carborane electrochemistry.


Assuntos
Boranos , Boro , Boranos/química , Boro/química , Carbono
12.
Angew Chem Int Ed Engl ; 61(20): e202201595, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35172030

RESUMO

While electrochemical ortho-selective C-H activations are well established, distal C-H activations continue to be underdeveloped. In contrast, we herein describe the electrochemical meta-C-H functionalization. The remote C-H bromination was accomplished in an undivided cell by RuCl3 ⋅3 H2 O with aqueous HBr. The electrohalogenation proceeded under exogenous ligand- and electrolyte-free conditions. Notably, pyrazolylarenes were meta-selectively brominated at the benzenoid moiety, rather than on the electron-rich pyrazole ring for the first time. Mechanistic studies were suggestive of an initial ruthenacycle formation, and a subsequent ligand-to-ligand hydrogen transfer (LLHT) process to liberate the brominated product.

13.
Angew Chem Int Ed Engl ; 61(20): e202117188, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35179817

RESUMO

Direct C-H functionalizations by electrocatalysis is dominated by strongly coordinating N(sp2 )-directing groups. In sharp contrast, direct electrocatalytic transformations of weakly-coordinating phenols remain underdeveloped. Herein, electrooxidative peri C-H alkenylations of challenging 1-naphthols were achieved by versatile rhodium(III) catalysis via user-friendly constant current electrolysis. The rhodaelectrocatalysis employed readily-available alkenes and a protic reaction medium and features ample scope, good functional group tolerance and high site- and stereoselectivity. The strategy was successfully applied to high-value, nitrogen-containing heterocycles, thereby providing direct access to uncommon heterocyclic motifs based on the dihydropyranoquinoline skeleton.

15.
J Am Chem Soc ; 144(2): 798-806, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35001624

RESUMO

Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is the most obvious disconnection to construct such compounds, the direct enantioselective C-H arylation through the concomitant induction of the chiral information remains extremely challenging and uncommon. Herein, the unprecedented earth-abundant 3d-metal-catalyzed atroposelective direct arylation is reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies and DFT computation revealed an uncommon mechanism for this asymmetric transformation, with the oxidative addition being the rate- and enantio-determining step. Excellent stereoselectivities were reached (up to 96% ee), while using an unusual N-heterocyclic carbene ligand bearing an essential remote substituent. Attractive dispersion interactions along with positive C-H---π interactions exerted by the ligand were identified as key factors to guarantee the excellent enantioselection.

16.
Angew Chem Int Ed Engl ; 61(11): e202114993, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35015329

RESUMO

C-oligosaccharides are pharmacologically relevant because they are more hydrolysis-resistant than O-oligosaccharides. Despite indisputable advances, C-oligosaccharides continue to be underdeveloped, likely due to a lack of efficient and selective strategies for the assembly of the interglycosidic C-C linkages. In contrast, we, herein, report a versatile and robust strategy for the synthesis of structurally complex C-oligosaccharides via catalyzed C(sp3 )-H activations. Thus, a wealth of complex interglycosidic (2→1)- and (1→1)-C-oligosaccharides becomes readily available by palladium-catalyzed C(sp3 )-H glycoside glycosylation. The isolation of key palladacycle intermediates and experiments with isotopically-labeled compounds identified a trans-stereoselectivity for the C(sp3 )-H glycosylation. The glycoside C(sp3 )-H activation manifold was likewise exploited for the diversification of furanoses, pyranoses and disaccharides.

17.
Angew Chem Int Ed Engl ; 61(17): e202117218, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35075763

RESUMO

Fungal infections caused by Candida species are among the most prevalent in hospitalized patients. However, current methods for the detection of Candida fungal cells in clinical samples rely on time-consuming assays that hamper rapid and reliable diagnosis. Herein, we describe the rational development of new Phe-BODIPY amino acids as small fluorogenic building blocks and their application to generate fluorescent antimicrobial peptides for rapid labelling of Candida cells in urine. We have used computational methods to analyse the fluorogenic behaviour of BODIPY-substituted aromatic amino acids and performed bioactivity and confocal microscopy experiments in different strains to confirm the utility and versatility of peptides incorporating Phe-BODIPYs. Finally, we have designed a simple and sensitive fluorescence-based assay for the detection of Candida albicans in human urine samples.


Assuntos
Candidíase , Sistema Urinário , Aminoácidos , Compostos de Boro , Candida , Candidíase/diagnóstico , Humanos , Peptídeos/química
18.
Chemistry ; 28(1): e202103837, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34714563

RESUMO

The use of electricity over traditional stoichiometric oxidants is a promising strategy for sustainable molecular assembly. Herein, we describe the rhoda-electrocatalyzed C-H activation/alkylation of several N-heteroarenes. This catalytic approach has been successfully applied to several arenes, including biologically relevant purines, diazepam, and amino acids. The versatile C-H alkylation featured water as a co-solvent and user-friendly trifluoroborates as alkylating agents. Finally, the rhoda-electrocatalysis with unsaturated organotrifluoroborates proceeded by paired electrolysis.


Assuntos
Metilação , Alquilação , Catálise
19.
Chem Sci ; 12(42): 14182-14188, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760203

RESUMO

Enantioselective palladaelectro-catalyzed C-H alkenylations and allylations were achieved with easily-accessible amino acids as transient directing groups. This strategy provided access to highly enantiomerically-enriched N-C axially chiral scaffolds under exceedingly mild conditions. The synthetic utility of our strategy was demonstrated by a variety of alkenes, while the versatility of our approach was reflected by atroposelective C-H allylations. Computational studies provided insights into a facile C-H activation by a seven-membered palladacycle.

20.
Chem Sci ; 12(39): 12971-12976, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34745527

RESUMO

Copper-catalyzed electrochemical direct chalcogenations of o-carboranes was established at room temperature. Thereby, a series of cage C-sulfenylated and C-selenylated o-carboranes anchored with valuable functional groups was accessed with high levels of position- and chemo-selectivity control. The cupraelectrocatalysis provided efficient means to activate otherwise inert cage C-H bonds for the late-stage diversification of o-carboranes.

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