92274-43-6Relevant articles and documents
Enantioconvergent Cross-Couplings of Alkyl Electrophiles: The Catalytic Asymmetric Synthesis of Organosilanes
Schwarzwalder, Gregg M.,Matier, Carson D.,Fu, Gregory C.
supporting information, p. 3571 - 3574 (2019/02/13)
Metal-catalyzed enantioconvergent cross-coupling reactions of alkyl electrophiles are emerging as a powerful tool in asymmetric synthesis. To date, high enantioselectivity has been limited to couplings of electrophiles that bear a directing group or a pro
Efficient analoging around ethionamide to explore thioamides bioactivation pathways triggered by boosters in Mycobacterium tuberculosis
Prieri, Marion,Frita, Rosangela,Probst, Nicolas,Sournia-Saquet, Alix,Bourotte, Marilyne,Déprez, Benoit,Baulard, Alain R.,Willand, Nicolas
, p. 35 - 46 (2018/10/02)
Ethionamide is a key antibiotic prodrug of the second-line chemotherapy regimen to treat tuberculosis. It targets the biosynthesis of mycolic acids thanks to a mycobacterial bioactivation carried out by the Baeyer-Villiger monooxygenase EthA, under the control of a transcriptional repressor called EthR. Recently, the drug-like molecule SMARt-420, which triggers a new transcriptional regulator called EthR2, allowed the derepression a cryptic alternative bioactivation pathway of ethionamide. In order to study the bioactivation of a collection of thioisonicotinamides through the two bioactivation pathways, we developed a new two-step chemical pathway that led to the efficient synthesis of eighteen ethionamide analogues. Measurements of the antimycobacterial activity of these derivatives, used alone and in combination with boosters BDM41906 or SMARt-420, suggest that the two different bioactivation pathways proceed via the same mechanism, which implies the formation of similar metabolites. In addition, an electrochemical study of the aliphatic thioisonicotinamide analogues was undertaken to see whether their oxidation potential correlates with their antitubercular activity measured in the presence or in the absence of the two boosters.
Synthesis and Cytotoxicity of 1,4-Naphthoquinone Oxime Derivatives
Zhang,Dong,Meng,Huang,Li
, p. 2388 - 2393 (2019/01/04)
A series of hydroxylated 1,4-naphthoquinone oximes were designed and synthesized. The in vitro cytotoxicity of these compounds was evaluated against five human cancer cell lines and human skin fibroblast cell line. Among them, compounds (1E,4E)-6-{1-[(5-Hydroxypentyl)oxy]-2,2-dimethylbut-3-en-1-yl}-5,8- dimethoxynaphthalene-1,4-dione dioxime and (1E,4E)-6-{1-[(6-Hydroxyhexyl)oxy]-2,2-dimethylbut-3-en-1-yl}-5,8-dimethoxynaphthalene-1,4-dione dioxime displayed higher cytotoxicity in three cancer cell lines than the positive drug 5-fluorouracil.
A general strategy for the synthesis of enantiomerically pure azetidines and aziridines through nickel-catalyzed cross-coupling
Jensen, Kim L.,Nielsen, Dennis U.,Jamison, Timothy F.
supporting information, p. 7379 - 7383 (2015/05/13)
Abstract In this communication, we report a straightforward synthesis of enantiomerically pure 2-alkyl azetidines. The protocol is based on a highly regioselective nickel-catalyzed cross-coupling of aliphatic organozinc reagents with an aziridine that fea
α-1-C-Butyl-1,4-Dideoxy-1,4-Imino-L-Arabinitol as a second-Generation iminosugar-based oral α-Glucosidase inhibitor for improving postprandial hyperglycemia
Kato, Atsushi,Hayashi, Erina,Miyauchi, Saori,Adachi, Isao,Imahori, Tatsushi,Natori, Yoshihiro,Yoshimura, Yuichi,Nash, Robert J.,Shimaoka, Hideyuki,Nakagome, Izumi,Koseki, Jun,Hirono, Shuichi,Takahata, Hiroki
, p. 10347 - 10362 (2013/02/23)
We report on the synthesis and the biological evaluation of a series of α-1-C-alkylated 1,4-dideoxy-1,4-imino-l-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. α-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 μM, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of α-1-C-butyl-LAB and miglitol are clearly different. Furthermore, α-1-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. α-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.
