90090-50-9Relevant articles and documents
Design and SAR of Withangulatin A Analogues that Act as Covalent TrxR Inhibitors through the Michael Addition Reaction Showing Potential in Cancer Treatment
Wang, Cheng,Li, Shang,Zhao, Jinhua,Yang, Huali,Yin, Fucheng,Ding, Ming,Luo, Jianguang,Wang, Xiaobing,Kong, Lingyi
, p. 11195 - 11214 (2020)
The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activity and other diverse pharmacological activities. To improve activity and targeting, we designed and prepared 41 semisynthetic analogues of WA. Biological evaluation indicated that the most promising compound 13a displayed the most significant effect on HT-29 cells (human colon cancer cells) (IC50 = 0.08 μM). A structure-activity relationship study indicated that α,β-unsaturated ketones and ester are necessary groups, allowing 13a to undergo Michael addition reactions with mercaptan and selenol. Liquid chromatography-mass spectrometry (LC-MS) analysis confirmed that 13a modified selenocysteine 498 (U) residues in the redox centers of TrxR, resulting in enzyme inhibition. Therefore, compound 13a acts as a novel TrxR inhibitor and may be a promising candidate for cancer intervention.
Exploring the scope of tandem palladium and isothiourea relay catalysis for the synthesis of α-amino acid derivatives
Bitai, Jacqueline,Slawin, Alexandra M.Z.,Cordes, David B.,Smith, Andrew D.
supporting information, (2020/07/27)
The scope and limitations of a tandem N-allylation/[2,3]-rearrangement protocol are investigated through the incorporation of a variety of functional groups within an allylic phosphate precursor. This method uses readily accessible N,N-dimethylglycine aryl esters and functionalized allylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequent enantioselective [2,3]-sigmatropic rearrangement, promoted by the chiral isothiourea tetramisole, generates α-amino acid derivatives with two contiguous stereocenters. The incorporation of electron-withdrawing ester and amide groups gave the best results, furnishing the desired products in moderate to good yields (29-70percent), with low diastereocontrol (typically 60:40 dr) but high enantioselectivity (up to 90:10 er). These results indicate that substrate-catalyst interactions in the proposed transition state are sensitive to the substitution pattern of the substrates.
Experimental and theoretical investigation of the reaction of secondary amines with maleic anhydride
Kour, Manjinder,Gupta, Raakhi,Bansal, Raj K.
, p. 1247 - 1253 (2017/11/27)
The reaction of secondary amines, namely 1-methylpiperazine, pyrrolidine, morpholine, 2-methylpiperidine, and diethylamine, with maleic anhydride has been investigated experimentally and theoretically at the DFT level. Under kinetic control, i.e. at -78°C
