RESUMO
The site-selective modification of quinolines and their analogs has emerged as a pivotal topic in medicinal chemistry and drug discovery. Herein, we describe the rhodium(III)-catalyzed C8-alkylation of quinoline N-oxides with maleimides as alkylating agents, resulting in the formation of bioactive succinimide-containing quinoline derivatives. The reaction proceeds under mild conditions with complete functional group tolerance.
Assuntos
Quinolinas , Ródio , Alquilação , Catálise , Maleimidas , ÓxidosRESUMO
The direct methylation of N-heterocycles is an important transformation for the advancement of pharmaceuticals, agrochemicals, functional materials, and other chemical entities. Herein, the unprecedented C(sp2 )-H methylation of iminoamido heterocycles as nucleoside base analogues is described. Notably, trimethylsulfoxonium salt was employed as a methylating agent under aqueous conditions. A wide substrate scope and excellent level of functional-group tolerance were attained. Moreover, this method can be readily applied to the site-selective methylation of azauracil nucleosides. The feasibility of gram-scale reactions and various transformations of the products highlight the synthetic potential of the developed method. Combined deuterium-labeling experiments aided the elucidation of a plausible reaction mechanism.
RESUMO
The preparation of phthalazinone derivatives is pivotal for their utilization as pharmaceutical agents and other entities. Herein, we report the phthalazinone-assisted carbon-nitrogen bond forming reaction using dioxazolones as robust amidation sources under Rh(III) catalysis. The broad functional group tolerance and complete site-selectivity are observed. Notably, a series of transformations of synthesized compounds into biologically relevant N-heterocycles demonstrates the applicability of the developed methodology.
RESUMO
The facile synthesis of hydroxymethylated indole derivatives is crucial for their further development as pharmaceutical compounds and other synthetic purposes. Herein, we describe the ruthenium(II)-catalyzed hydroxymethylation of indolines and other N-heterocycles using paraformaldehyde as an abundant C1 feedstock. A wide substrate scope range and high levels of site selectivity as well as functional group tolerance were observed.
RESUMO
The ruthenium(II)-catalyzed C-H aminocarbonylation of N-(hetero)aryl-7-azaindoles with isocyanates is described. The excellent site selectivity at the ortho-position within the N-(hetero)aryl ring was observed to provide ortho-amidated N-(hetero)aryl-7-azaindoles under the mild reaction conditions. The resulting 7-azaindole derivatives can be readily transformed into 7-azaindoles containing carboxylic acid and alkyl amine functional groups.
RESUMO
The synthesis and antidiabetic evaluation of ethyl 2-[2,3,4-trimethoxy-6-(1-octanoyl)phenyl]acetate (TMPA) and its structural analogs are described. The construction of TMPA derivatives has been successfully achieved in only two steps, which involve the iridium(III)-catalyzed α-alkylation of acetophenones with alcohols and the ketone-directed iridium(III)- or rhodium(III)-catalyzed redox-neutral C-H alkylation of α-alkylated acetophenones using Meldrum's diazo compounds. This synthetic protocol efficiently provides a range of TMPA derivatives with site selectivity and functional group compatibility. In addition, the site-selective demethylation of TMPA derivative affords the naturally occurring phomopsin C in good yield. Moreover, all synthetic compounds were screened for in vitro adenosine 5'-monophosphate-activated protein kinase (AMPK) activation using HepG2 cells. Furthermore, TMPA (5ac) and 5cd showing the most potent AMPK activation were treated for the in vivo antidiabetic experiment. Notably, our synthetic compound 5cd was found to display the powerful antidiabetic effect, stronger than that of metformin and TMPA (5ac).
RESUMO
The rhodium(iii)-catalyzed C(sp3)-H amination reaction of 8-methylquinolines and azodicarboxylates is described. A cationic rhodium catalyst in the presence of lithium acetate and lithium carbonate was found to be an optimal catalytic system for the construction of quinolin-8-ylmethanamine derivatives, which were evaluated for in vitro cytotoxicity against human breast adenocarcinoma cells (MCF-7) and human prostate adenocarcinoma cells (LNCaP).
RESUMO
The rhodium(III)-catalyzed direct cross-coupling reaction of electron-deficient acrylamides with maleimides is described. This protocol displays broad functional group tolerance and high efficiency, which offers a new opportunity to access highly substituted succinimides. Dependent on the substituent positions of acrylamides and reaction conditions, olefin migrated products were obtained with high regio- and stereoselectivity.
RESUMO
The rhodium(III)-catalyzed cross-coupling reaction of 8-methylquinolines and maleimides is described. In contrast to the C(sp(2))-H functionalization, a first catalytic functionalization of sp(3) C-H bonds with maleimides is reported. This protocol provides a facile access to various succinimide scaffolds on 8-methylquinolines via a direct C-H cleavage approach.