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1.
Chemistry ; 29(35): e202300530, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-36919521

RESUMO

A dual catalytic approach combining photocatalyst and selenium-π-acid synergy has been used to cyclized of N-propargylamides. This method offers readily access to oxazole aldehydes under chemical oxidant-free conditions with low catalyst loadings, where air acts as a terminal and gratuitous oxidant. The reaction is demonstrated with a range of substrates, including aryl and alkyl propargyl amides, and in the late-stage functionalization of several amide-containing drug molecules. Mechanistic studies suggest that the acridinium catalyst is able to oxidize diselenide and generate singlet oxygen (1 O2 ), which is responsible for this transformation.


Assuntos
Selênio , Ciclização , Catálise , Oxidantes , Amidas/química
2.
J Org Chem ; 88(11): 7431-7447, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37219840

RESUMO

Three-component selenofunctionalization processes of olefins, diselenides and sulfonamides, water, alcohols, or acids utilizing 1-fluoropyridinium triflate (FP-OTf) as a reaction promoter are reported. Under the optimal conditions, a broad range of vicinally functionalized selenide derivatives was accessible with high yields and excellent functional group compatibilities. Mechanistic studies revealed that the FP-OTf played a key role in this selenofunctionalization process.

3.
J Org Chem ; 87(21): 14609-14622, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36283048

RESUMO

Intermolecular carboselenenylation of easily accessible alkenes by utilizing diselenides and N-fluorobenzenesulfonimide (NFSI) under metal-free and mild conditions is reported. Preliminary mechanistic studies indicate that the oxidation of diselenide by NFSI through a single-electron-transfer process produces an active selenenyl cationic radical species that initiates the intermolecular carboselenenylation of olefins, forming key Se-C and C-C bonds. Under optimized conditions, a broad spectrum of functionally and structurally diverse selenoether derivatives with promising yields is accessed with a very high functional group tolerance.

4.
Org Biomol Chem ; 20(2): 420-426, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34913464

RESUMO

A time-economical and robust synthesis of various selenofunctionalized heterocycles was accomplished via I2O5-mediated selenocyclizations of olefins with diselenides. Using this method, 116 selenomethyl-substituted heterocycles were synthesized with up to 97% isolated yield in minutes. Additional features of this new protocol include the use of an inorganic oxidant, mild conditions, and easy operation. Preliminary investigations suggest that the transformation operates through selenenyl iodide-induced electrophilic cyclization.

5.
Org Biomol Chem ; 20(27): 5463-5469, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35772180

RESUMO

A simple and efficient method for the regioselective selenation of electron-rich arenes by employing non-metal inorganic iodine pentoxide (I2O5) as a reaction promoter under ambient conditions has been developed. The present protocol showed broad functional group tolerance and easy-to-operate and time-economical features. Additionally, this protocol also allows access to 3-seleno and 3-thiocyanoindoles by the use of readily available selenocyanate and thiocyanate salts. A mechanistic study indicated that the transformation operated through selenenyl iodide-induced electrophilic substitution processes.

6.
J Org Chem ; 86(7): 5292-5304, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33706517

RESUMO

A three-component reaction of olefin, diselenide and water, alcohols, phenol, carboxylic acid, or amine by a commercially available hypervalent iodine(III) reagent, PhIO, was developed. This method provides access to a wide range of vicinally functionalized selenoderivatives under ambient conditions with mostly excellent yields and high diastereoselectivity. The developed reaction displays high levels of functional group compatibility and is suitable for the late-stage functionalization of styrene-functionalized biomolecules. Preliminary investigations on the mechanism of the reaction are also presented.


Assuntos
Alcenos , Iodobenzenos , Álcoois , Estrutura Molecular
7.
J Org Chem ; 84(23): 15677-15684, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31689366

RESUMO

A photocatalytic strategy for the synthesis of γ-ketoesters was reported. Using DMSO as both the solvent and terminal oxidant, oxidative coupling of vinylarenes with bromocarboxylates proceeded readily, giving a variety of γ-ketoesters in good isolated yields and with a broad functional-group tolerance.

8.
Org Biomol Chem ; 16(40): 7454-7460, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30264840

RESUMO

A metal-free cyclization of olefinic dicarbonyl compounds for the synthesis of various 5-halomethyl-4,5-dihydrofurans is presented. Using (diacetoxyiodo)benzene as the reaction promoter and halotrimethylsilane as the halogen source, the intramolecular haloenolcyclization of the 2-allyl-1,3-dicarbonyl compounds smoothly proceeded, leading to the corresponding 5-halomethyl-4,5-dihydrofurans in good to excellent isolated yields. Moreover, the resulting 5-iodomethyl products could be converted to functionalized furans in almost quantitative yields by treatment with DBU followed by acid-catalyzed rearrangement. The reactions could be carried out on a gram scale and did not require harsh reaction conditions. The good isolated yields, mild conditions, and operational simplicity make this reaction a viable method for the construction of different dihydrofuran and furan structures.

9.
Org Biomol Chem ; 16(38): 7012-7018, 2018 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-30232498

RESUMO

A metal-free cyclization of N-propargylamides for the synthesis of various oxazolines and oxazoles via a 5-exo-dig process is presented. Using (diacetoxyiodo)benzene (PIDA) as a reaction promoter and lithium iodide (LiI) as an iodine source, intramolecular iodooxygenation of N-propargylamides proceeded readily, leading to the corresponding (E)-5-iodomethylene-2-oxazolines in good to excellent isolated yields. In addition, using the PhI(OAc)2/LiI system, N-propargylamides can be converted to the corresponding oxazole-5-carbaldehydes in the presence of oxygen under visible light irradiation. The resulting products can be further converted into various oxazoline and oxazole derivatives after simple derivatizations, and this method ultimately offers an efficient route to a variety of biologically active structures.

10.
J Org Chem ; 82(2): 1218-1223, 2017 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-27997193

RESUMO

A concise and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol, a key building block for several clinical and experimental HIV protease inhibitors including the highly important drug darunavir, was achieved via a one-pot procedure using furan and Cbz-protected glycol aldehyde as starting materials. A [2+2]-photocycloaddition between both reactants which can be prepared from wood-based starting materials according to the principles of xylochemistry, followed by hydrogenation and lipase-catalyzed kinetic resolution afforded the target compound in high yield and up to 99% ee.


Assuntos
Química Orgânica/métodos , Furanos/síntese química , Inibidores da Protease de HIV/síntese química , Furanos/química , Estrutura Molecular , Estereoisomerismo
11.
J Org Chem ; 81(14): 6142-8, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27314476

RESUMO

A concise and modular synthesis of phenanthroindolizidine alkaloids was achieved by combining iodoaminocylization with a free radical cyclization approach. The route described allowed the preparation of (±)-tylophorine, (±)-antofine, and (±)-deoxypergularinine in six steps. When commercially available l-prolinol was used as a chiral building block, (S)-(+)-tylophorine was also synthesized in 49% yield and >99% ee over five linear steps.


Assuntos
Alcaloides/síntese química , Indolizinas/química , Indolizinas/síntese química , Isoquinolinas/química , Fenantrenos/química , Fenantrolinas/síntese química , Alcaloides/química , Química Orgânica , Ciclização , Radicais Livres , Indóis , Espectroscopia de Ressonância Magnética , Pirrolidinas , Estereoisomerismo , Relação Estrutura-Atividade , Temperatura
12.
J Org Chem ; 81(12): 5144-61, 2016 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-27214117

RESUMO

A general and practical method for the preparation of trans-2-substituted-4-halopiperidines and cis-2-substituted-4-halotetrahydropyrans is reported. Using 5 mol % of AlCl3 as the catalyst and 2 equiv of trimethylsilyl halides as the halide sources, aza-Prins cyclization of N-tosyl homoallylamine or Prins cyclization of homoallylic alcohol with carbonyl compounds could be readily realized, giving the corresponding trans-2-substituted-4-halopiperidines or cis-2-substituted-4-halotetrahydropyrans in high yields and satisfactory diastereoselectivity.

13.
J Org Chem ; 80(22): 11339-50, 2015 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-26501791

RESUMO

A new method for the construction of oxazoline moiety was detailed. Using (diacetoxyiodo)benzene (PIDA) as the reaction promoter and halotrimethylsilane as the halogen source, intramolecular halooxygenation and halothionation of N-allylcarboxamides/N-allylcarbothioamides proceeded readily, leading to the corresponding 5-halomethyloxazolines/5-halomethylthiazolines in good to excellent isolated yields. The 5-halomethyl products could be converted to different derivatives via conventional nucleophilic substitution methods. The reactions were carried out using easily available starting materials, and did not need harsh reaction conditions. All these features made this reaction a viable method for the construction of different oxazoline and thiazoline structures.

14.
Angew Chem Int Ed Engl ; 54(43): 12636-9, 2015 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-26331979

RESUMO

A direct and catalyst-free method for the intramolecular aminoboration of unfunctionalized olefins is reported. In the presence of BCl3 (1 equiv) as the sole boron source, intramolecular aminoboration of sulfonamide derivatives of 4-penten-1-amines, 5-hexen-1-amines, and 2-allylanilines proceeded readily without the use of any catalyst. The boronic acids obtained after hydrolysis could be converted into the corresponding pinacol borates in a straightforward manner by treatment with pinacol under anhydrous conditions.


Assuntos
Alcenos/química , Aminas/química , Boro/química , Ácidos Borônicos/química , Alcenos/síntese química , Aminação , Aminas/síntese química , Ácidos Borônicos/síntese química , Catálise , Hidrólise
15.
J Org Chem ; 79(21): 10094-109, 2014 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-25310379

RESUMO

A metal-free method for intramolecular halocyclization of unfunctionalized olefins was detailed. (Diacetoxyiodo)benzene (PIDA) was very effective for haloamidation, haloetherification, and halolactonization of unfunctionalized olefins. In the presence of 1.1 equiv of PIDA and suitable halogen sources, a variety of unfunctionalized olefins could be converted to the corresponding 1,2-bifunctional cyclic skeletons in good to excellent isolated yields, and key intermediates for biologically interesting compounds could be obtained in high yields under mild conditions via nucleophilic substitution of the thus obtained halocyclization products.


Assuntos
Alcenos/química , Derivados de Benzeno/química , Iodetos/química , Catálise , Ciclização , Hidrocarbonetos Halogenados , Estrutura Molecular
16.
ChemSusChem ; : e202301511, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043608

RESUMO

A photochemical method based on visible-light irradiation (blue LEDs/sunlight) has been developed for the intermolecular hydroamination and hydroetherification of electron-rich alkenes. This photochemical method is compatible with a wide range of azoles and electron-rich alkenes, such as vinyl ethers, vinyl sulfides and enamides, and is performed with low concentrations of photocatalyst (1000 ppm). Comprehensive mechanistic studies indicate that this process is initiated by the formation of an active radical cation intermediate through single electron oxidation of azole, which is mediated by excited Acr-Mes+ BF4-.

17.
RSC Adv ; 14(32): 23147-23151, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39040696

RESUMO

Zn(OTf)2-catalyzed intra- and intermolecular selenofunctionalization of alkenes was achieved with electrophilic N-phenylselenophthalimide. This method provides straightforward and efficient access to various seleno-substituted heterocycles and vicinal Se heteroatom-disubstituted molecules under mild conditions. This reaction is compatible with various substrates/functional groups, and preliminary studies on the reaction mechanistic were also conducted.

18.
Theranostics ; 12(6): 2535-2548, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401826

RESUMO

Rationale: Precise diagnosis and effective therapy of the tumor microenvironment (TME) remains a challenge. Fluorescence tracers for monitoring primary tumors are currently reported; however, they face challenges in accurately delineating tumors in real-time during surgery, including interference from the background and insufficient accumulation of imaging reagents at tumor sites. Additionally, although the natural product podophyllotoxin (PPT) had potent and broad anti-tumor activity, the poor tumor target specificity and high toxicity of PPT extremely limited its clinical application. Methods: In the current study, a novel theranostic agent PBB was designed and synthesized by coupling the natural chemotherapeutic drug PPT with a near-infrared (NIR) fluorescence probe hemicyanine (CyOH) via redox-responsive thiolactate linker and introducing biotin to CyOH to enhance the active target ability. The activation mechanism of PBB was characterized by absorption spectra, fluorescence spectra, and HPLC. Subsequently, we investigated its imaging action, anti-tumor activity, and toxicity in vitro and in vivo. Results:In vitro experiments, PBB was verified to possess a ROS/GSH-responsive molecular switch, impelling PBB to release a fluorescent fragment and active drug PPT and selectively lighting up tumor cells but not the normal cells. As such, PBB was demonstrated to selectively inhibit the growth of tumor cells by inducing intracellular accumulation of ROS and MMP depolarization. More importantly, PBB significantly suppressed hepatic tumor growth and minimized the adverse effects caused by PPT, including acute toxicity and impaired liver function. Finally, the NIR fluorescence accumulated in the tumor tissue and stayed continuous for over 24h, and PBB provided precise visualization and highly selective fluorescence diagnosis to guide tumor resection. Conclusions: Therefore, the multilevel targeting theranostic agent provided a novel tool for precise diagnosis, real-time monitoring, and efficient tumor chemotherapy with high safety.


Assuntos
Nanopartículas , Nanomedicina Teranóstica , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
19.
J Med Chem ; 65(15): 10393-10407, 2022 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-35877176

RESUMO

A novel theranostic co-prodrug SCB has been designed by combining a co-prodrug from CDDO-Me and SAHA with a biotin-coupled near-infrared (NIR) probe hemicyanine via redox-responsive linker thiolactate to enhance the tumor theranostic efficacy and reduce the toxic side effects using both active and passive targeting strategies. SCB displayed reactive oxygen species (ROS)- and glutathione (GSH)-dependent release of NIR fluorescence and two parent drugs. Furthermore, the administration of SCB caused selective illumination of the tumor tissues for >24 h, thereby guiding precise removal of a tumor from intraoperative mice. Importantly, SCB exhibited highly efficient tumor inhibition, exerted selective combination therapy through prodrug mode, and minimized the adverse effects. Finally, SCB induced mitochondrial depolarization, DNA damage, and cell apoptosis through ROS generation and downregulation of HDAC6 protein, as verified by H2AX, Bax, cleaved-PARP, and Mcl-1 proteins. Thus, we suggest that SCB can provide a new platform for both precise diagnosis-guided tumor removal and selective combination therapy with high safety.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Animais , Linhagem Celular Tumoral , Quimioterapia Combinada , Glutationa/metabolismo , Camundongos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Oxirredução , Medicina de Precisão , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica
20.
Chem Commun (Camb) ; 57(82): 10755-10758, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34585686

RESUMO

The Complexity to Diversity (CtD) strategy, a strategy for the synthesis of stereochemically complex and structurally diverse small molecules from natural products using ring-distortion reactions, was applied in the synthesis of a 47-member compound collection from the natural product griseofulvin. A Tsuji-Trost allylation and oxa-Michael cyclization tandem reaction was used for the first time in the CtD strategy to generate complex ring fused compounds.

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