814-68-6Relevant articles and documents
The molecular design of photo-curable and high-strength benzoxazine for 3D printing
Lu, Yong,Ng, Kok Wei Joseph,Chen, Hui,Chen, Xuelong,Lim, Song Kiat Jacob,Yan, Weili,Hu, Xiao
supporting information, p. 3375 - 3378 (2021/04/07)
Low viscosity photo-curable benzoxazines (BZs) are designed and synthesized for use in stereolithography 3D printing. An initial investigation shows that the thermally polymerized polybenzoxazines (PBZs) have remarkably highTg(264 °C) and flexural modulus (4.91 GPa) values. Subsequently, the formulated photoprintable resins are employed for use in high-resolution projection micro-stereolithography (PμSL) printing. Complex PBZ 3D structures can be achieved from the as-printed objects after they are thermally treated. These findings advance the design of BZ monomers for photopolymerization-based 3D printing and offer a method for the efficient fabrication of high-performance thermosets for various demanding engineering applications.
Asymmetric Allylation Catalyzed by Chiral Phosphoric Acids: Stereoselective Synthesis of Tertiary Alcohols and a Reagent-Based Switch in Stereopreference
Lazzarotto, Mattia,Hartmann, Peter,Pletz, Jakob,Belaj, Ferdinand,Kroutil, Wolfgang,Payer, Stefan E.,Fuchs, Michael
supporting information, p. 3138 - 3143 (2021/04/28)
The substrate scope of the asymmetric allylation with zinc organyls catalyzed by 3,3-bis(2,4,6-triisopropylphenyl)-1,1-binaphthyl-2,2-diyl hydrogenphosphate (TRIP) has been extended to non-cyclic ester organozinc reagents and ketones. Tertiary chiral alcohols are obtained with ee's up to 94% and two stereogenic centers can be created. Compared to the previous lactone reagent the stereopreference switches almost completely, proving the fact that the nature of the organometallic compound is of immense importance for the asymmetry of the product. (Figure presented.).
Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities
Feng, Jia-Hao,He, Qi-Wei,Hou, Ji-Qin,Hu, Xiao-Long,Long, Huan,Wang, Bao-Lin,Wang, Hao,Wang, Quan,Wang, Rong,Ye, Wen-Cai,Zhang, Li-Xin,Zhang, Xiao-Qi
, p. 1954 - 1966 (2021/07/20)
Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.
Zinc-Catalyzed β-Functionalization of Cyclopropanols via Enolized Homoenolate
Sekiguchi, Yoshiya,Yoshikai, Naohiko
supporting information, p. 18400 - 18405 (2021/11/16)
We report herein a zinc-catalyzed β-allylation of cyclopropanols with Morita-Baylis-Hillman (MBH) carbonates with retention of the cyclopropane ring. The reaction is promoted by a zinc aminoalkoxide catalyst, affording cyclopropyl-fused α-alkylidene-δ-valerolactone derivatives in moderate to good yields. Mechanistic experiments suggest that the present reaction does not proceed via direct β-C-H cleavage of the cyclopropanol, but involves zinc homoenolate and its enolization to generate a key bis-nucleophilic species. α-Allylation of this "enolized homoenolate"with MBH carbonate would be followed by regeneration of the cyclopropane ring and irreversible lactonization. The enolized homoenolate mechanism has also been proven to allow for β-functionalization with alkylidenemalononitrile as the reaction partner. A sequence of the present reaction and known cyclopropanol transformation provides an opportunity to transform a simple cyclopropanol into α,β- or β,β-difunctionalized ketones.
An efficient approach for the synthesis of new (±)-coixspirolactams
Nascimento, Vinicius R.,Suenaga, Melissa L. S.,Andrade, Leandro H.
supporting information, p. 5458 - 5465 (2020/08/03)
Coixspirolactams, spiro[oxindole-γ-lactones], are found in adlay seeds and exhibit anticancer activity. A novel synthetic methodology was developed to enable an easy access to (±)-coixspirolactam A and a large number of new coixspirolactams in excellent overall yields. The exquisite exploitation of formamide reactivity was essential for the construction of oxindole and lactone scaffolds. This journal is
Design, synthesis and 3D-QSAR analysis of novel thiopyranopyrimidine derivatives as potential antitumor agents inhibiting A549 and Hela cancer cells
Zhao, Bingbing,Zhao, Chengwu,Hu, Xiaohan,Xu, Shan,Lan, Zhou,Guo, Yuping,Yang, Zunhua,Zhu, Wufu,Zheng, Pengwu
, (2019/11/03)
Four series of thiopyranopyrimidine AZD9291 derivatives containing acrylamide structure were designed, synthesized and evaluated for their antiproliferative activity against A549 and Hela cancer cells. Most of the compounds exhibited excellent antiproliferative activity against A549 cells. Moreover, the compounds with indole ring fluorine substituted exhibited better antiproliferative activity against Hela cells. The most promising compound 23g exhibited excellent enzymatic inhibitory activity and selectivity for EGFRL858R/T790M double mutations. The IC50 value against EGFRL858R/T790M kinase was 16 nM. The compound 23g inhibits selectively against the mutated form of EGFR, with the selectivity more than 125-fold. Furthermore, compound 23g also inhibited A549 cells, Hela cells and H1975 cells proliferation at a low concentration, and the IC50 values were 0.057 μM, 0.104 μM and 0.916 μM, respectively. To further investigate the QSARs of thiopyranopyrimidine derivatives, the CoMFA (q [2] = 0.765, r2 = 0.965) and CoMSIA (q [2] = 0.875, r2 = 0.956) models on Hela cancer cells were established. The generated 3D-QSAR model was validated to be reliable and can be used for further design and optimization of novel and selective EGFR inhibitors.
Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors
Xie, Yiyue,Tummala, Padmaja,Oakley, Aaron J.,Deora, Girdhar Singh,Nakano, Yuji,Rooke, Melissa,Cuellar, Matthew E.,Strasser, Jessica M.,Dahlin, Jayme L.,Walters, Michael A.,Casarotto, Marco G.,Board, Philip G.,Baell, Jonathan B.
, p. 2894 - 2914 (2020/04/08)
Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1β and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhibitors that act by covalent labeling. In this study, structure-activity relationship (SAR) elaboration of the reported GSTO1-1 inhibitor C1-27 was undertaken. Compounds were evaluated for inhibitory activity toward purified recombinant GSTO1-1 and for indicators of target engagement in cell-based assays. As covalent inhibitors, the kinact/KI values of selected compounds were determined, as well as in vivo pharmacokinetics analysis. Cocrystal structures of key novel compounds in complex with GSTO1-1 were also solved. This study represents the first application of a biochemical assay for GSTO1-1 to determine kinact/KI values for tested inhibitors and the most extensive set of cell-based data for a GSTO1-1 inhibitor SAR series reported to date. Our research culminated in the discovery of 25, which we propose as the preferred biochemical tool to interrogate cellular responses to GSTO1-1 inhibition.
Palladium-catalyzed remote C-H functionalization of 2-aminopyrimidines
Das, Animesh,Jana, Akash,Maji, Biplab
supporting information, p. 4284 - 4287 (2020/04/27)
A straightforward strategy was developed for the arylation and olefination at the C5-position of the N-(alkyl)pyrimidin-2-amine core with readily available aryl halides and alkenes, respectively. This approach was highly regioselective, and the transformation was achieved based on two different (Pd(ii)/Pd(iv)) and (Pd(0)/Pd(ii)) catalytic cycles.
Design, synthesis and agricultural evaluation of derivatives of N-Acyl-N-(m-fluoro-benzyl)-6-amino-coumarin
Ding, Yin-hao,Dong, Jing-jing,Feng, Bai-cheng,Hao, Shuang-hong,Jin, Yan,Wei, Yan
supporting information, (2020/08/19)
ABTRACT: This study aims to design and synthesize a series of N-Acyl-N-(m-fluoro- benzyl)-6- amino-coumarins through the principle of active substructure stitching, which are based on the core structure of N-(m-fluoro-benzyl)-6-amino-coumarin. The structures of target compounds e1–e25 have been characterized by 1H NMR, 13C NMR, ESI-MS and elemental analysis. Meanwhile, their agricultural activity have been evaluated in two weeds (Amaranth and Crabgrass) and four widespread noxious pathogens (V.mali, B.cinerea, F.axysporium and C.bacteria). The herbicidal activity results showed that almost all synthetic molecules have a greater impact on the stem system than on the root. Excellent inhibition rates were discovered from compounds e2–e5 and e20–e23 against Amaranth on stems, which were above 58percent(20 mg/L), 68percent(100 mg/L) respectively. Compounds e2 and e21 also exhibited striking inhibition on stems growth of both weeds. Anti-pathogenic activity showed that all the compounds exerted a better inhibitory activity on B.cinerea at 20 ppm compared to control carbendazim. All the heterocyclic substituted compounds (e17–e24, >57percent) made a better influence than the control (54.1percent) at the100 ppm. This research provides promising herbicidal and anti-pathogenic agents that have the better effects and can be potential for further development.
Macrolactam Synthesis via Ring-Closing Alkene-Alkene Cross-Coupling Reactions
Goh, Jeffrey,Loh, Teck-Peng,Maraswami, Manikantha
supporting information, p. 9724 - 9728 (2020/12/21)
Reported herein is a practical method for macrolactam synthesis via a Rh(III)-catalyzed ring closing alkene-alkene cross-coupling reaction. The reaction proceeded via a Rh-catalyzed alkenyl sp2 C-H activation process, which allows access to macrocyclic molecules of different ring sizes. Macrolactams containing a conjugated diene framework could be easily prepared in high chemoselectivities and Z,E stereoselectivities.
