6457-49-4Relevant articles and documents
C-H Alkylation of Aldehydes by Merging TBADT Hydrogen Atom Transfer with Nickel Catalysis
Murugesan, Vetrivelan,Ganguly, Anirban,Karthika, Ardra,Rasappan, Ramesh
supporting information, p. 5389 - 5393 (2021/07/21)
Catalyst controlled site-selective C-H functionalization is a challenging but powerful tool in organic synthesis. Polarity-matched and sterically controlled hydrogen atom transfer (HAT) provides an excellent opportunity for site-selective functionalization. As such, the dual Ni/photoredox system was successfully employed to generate acyl radicals from aldehydes via selective formyl C-H activation and subsequently cross-coupled to generate ketones, a ubiquitous structural motif present in the vast majority of natural and bioactive molecules. However, only a handful of examples that are constrained to the use of aryl halides are developed. Given the wide availability of amines, we developed a cross-coupling reaction via C-N bond cleavage using the economic nickel and TBADT catalyst for the first time. A range of alkyl and aryl aldehydes were cross-coupled with benzylic and allylic pyridinium salts to afford ketones with a broad spectrum of functional group tolerance. High regioselectivity toward formyl C-H bonds even in the presence of α-methylene carbonyl or α-amino/oxy methylene was obtained.
Can Heteroarenes/Arenes Be Hydrogenated Over Catalytic Pd/C Under Ambient Conditions?
Tanaka, Nao,Usuki, Toyonobu
, p. 5514 - 5522 (2020/07/24)
Hydrogenation of over a dozen aromatic compounds, including both heteroarenes and arenes, over palladium on carbon (Pd/C, 1–100 molpercent) with H2-balloon pressure at room temperature is reported. Analyses using pyridine as a model substrate revealed that acetic acid was the best solvent, as using only 1 molpercent Pd/C provided piperidine quantitatively. Substrate scope analysis and density functional theory calculations indicated that reaction rates are highly dependent on frontier molecular orbital characteristics and the steric bulkiness of substituents. Moreover, the established method was used for the concise synthesis of the anti-Alzheimer drug donepezil (Aricept?).
Novel multitarget-directed ligands targeting acetylcholinesterase and σ1 receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase
Lalut, Julien,Santoni, Gianluca,Karila, Delphine,Lecoutey, Cédric,Davis, Audrey,Nachon, Florian,Silman, Israel,Sussman, Joel,Weik, Martin,Maurice, Tangui,Dallemagne, Patrick,Rochais, Christophe
supporting information, p. 234 - 248 (2018/11/24)
Pleiotropic intervention may be a requirement for effective limitation of the progression of multifactorial diseases such as Alzheimer's Disease. One approach to such intervention is to design a single chemical entity capable of acting on two or more targets of interest, which are accordingly known as Multi-Target Directed Ligands (MTDLs). We recently described donecopride, the first MTDL able to simultaneously inhibit acetylcholinesterase and act as an agonist of the 5-HT4 receptor, which displays promising activities in vivo. Pharmacomodulation of donecopride allowed us to develop a novel series of indole derivatives possessing interesting in vitro activities toward AChE and the σ1 receptor. The crystal structures of complexes of the most promising compounds with Torpedo californica AChE were solved in order to further understand their mode of inhibition.
