42428-03-5Relevant academic research and scientific papers
Synthesis of 3-nitroindoles by sequential paired electrolysis
Kilmartin, Paul A.,Lindsay, Ashley C.,Sperry, Jonathan
supporting information, p. 7903 - 7913 (2021/09/28)
3-Nitroindoles are synthetically versatile intermediates but current methods for the preparation hinder their widespread application. Herein, we report that nitroenamines undergo electrochemical cyclisation to 3-nitroindoles in the presence of potassium iodide. Detailed control experiments and cyclic voltammogram studies infer the reaction proceedsviaa sequential paired electrolysis process, beginning with anodic oxidation of iodide (I?) to the iodine radical (I˙), which facilitates cyclisation of the nitroenamine to give a 3-nitroindolinyl radical. Cathodic reduction and protonation generates a 3-nitroindoline that upon oxidation forms the 3-nitroindole.
Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes
Bai, Feifei,Fang, Jianguo,Song, Zi-Long,Zhang, Baoxin
, p. 2214 - 2231 (2020/03/06)
Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of the endogenous antioxidant defense system are promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine-or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
Ketoreductase catalyzed stereoselective bioreduction of α-nitro ketones
Wang, Zexu,Wu, Xiaofan,Li, Zhining,Huang, Zedu,Chen, Fener
supporting information, p. 3575 - 3580 (2019/04/14)
We report here the stereoselective bioreduction of α-nitro ketones catalyzed by ketoreductases (KREDs) with publicly known sequences. YGL039w and RasADH/SyADH were able to reduce 23 class I substrates (1-aryl-2-nitro-1-ethanone (1)) and ten class II substrates (1-aryloxy-3-nitro-2-propanone (4)) to furnish both enantiomers of the corresponding β-nitro alcohols, with good-to-excellent conversions (up to >99%) and enantioselectivities (up to >99% ee) being achieved in most cases. To the best of our knowledge, KRED-mediated reduction of class II α-nitro ketones (1-aryloxy-3-nitro-2-propanone (4)) is unprecedented. Select β-nitro alcohols, including the synthetic intermediates of bioactive molecules (R)-tembamide, (S)-tembamide, (S)-moprolol, (S)-toliprolol and (S)-propanolol, were stereoselectively synthesized in preparative scale with 42% to 90% isolated yields, showcasing the practical potential of our developed system in organic synthesis. Finally, the advantage of using KREDs with known sequence was demonstrated by whole-cell catalysis, in which β-nitro alcohol (R)-2k, the key synthetic intermediate of hypoglycemic natural product (R)-tembamide, was produced in a space-time yield of 178 g L?1 d?1 as well as 95% ee by employing the whole cells of a recombinant E. coli strain coexpressing RasADH and glucose dehydrogenase as the biocatalyst.
Biology-oriented drug synthesis (BIODS): In vitro β-glucuronidase inhibitory and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives
Salar, Uzma,Khan, Khalid Mohammed,Taha, Muhammad,Ismail, Nor Hadiani,Ali, Basharat,Qurat-ul-Ain,Perveen, Shahnaz,Ghufran, Mehreen,Wadood, Abdul
, p. 1289 - 1299 (2016/12/06)
Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS,1H -NMR and13C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50= 1.20 ± 0.01–60.30 ± 1.40 μM as compared to the standard D-saccharic acid 1,4-lactone (IC50= 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9–19, and 21–24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
Indium-mediated one-pot synthesis of benzoxazoles or oxazoles from 2-nitrophenols or 1-aryl-2-nitroethanones
Lee, Jung June,Kim, Jihye,Jun, Young Moo,Lee, Byung Min,Kim, Byeong Hyo
experimental part, p. 8821 - 8831 (2009/12/26)
One-pot reduction-triggered heterocyclizations from 2-nitrophenols to benzoxazoles and from 1-aryl-2-nitroethanones to oxazoles were investigated. In the presence of indium/AcOH in benzene at reflux, 2-nitrophenols and R-C(OMe)3 (R=H, Me, Ph) produced excellent yields of corresponding benzoxazoles within an hour. Similarly, 1-aryl-2-nitroethanones and Ph-C(OMe)3 in the presence of indium/AcOH in acetonitrile transformed into the corresponding oxazoles with good yields.
