21852-32-4Relevant articles and documents
Total synthesis of dehaloperophoramidine using a highly diastereoselective Hosomi-Sakurai reaction
Wilkie, Ross. P.,Neal, Andrew R.,Johnston, Craig A.,Voute, Nicholas,Lancefield, Christopher S.,Stell, Matthew D.,Medda, Federico,Makiyi, Edward F.,Turner, Emma M.,Stephen Ojo,Slawin, Alexandra M. Z.,Lebl, Tomas,Mullen, Peter,Harrison, David J.,Ireland, Chris M.,Westwood, Nicholas J.
, p. 10747 - 10750 (2016)
The synthesis of dehaloperophoramidine, a non-halogenated derivative of the marine natural product perophoramidine, and its biological activity towards HCT116, HT29 and LoVo colorectal carcinoma cells is reported. A [3,3]-Claisen rearrangement and an epoxide opening/allylsilylation reaction installed the contiguous all-carbon quaternary stereocentres with the required relative stereochemistry.
Covalent Inhibition of Bacterial Urease by Bifunctional Catechol-Based Phosphonates and Phosphinates
Pagoni, Aikaterini,Grabowiecka, Agnieszka,Tabor, Wojciech,Mucha, Artur,Vassiliou, Stamatia,Berlicki, ?ukasz
supporting information, p. 404 - 416 (2021/01/13)
In this study, a new class of bifunctional inhibitors of bacterial ureases, important molecular targets for antimicrobial therapies, was developed. The structures of the inhibitors consist of a combination of a phosphonate or (2-carboxyethyl)phosphinate functionality with a catechol-based fragment, which are designed for complexation of the catalytic nickel ions and covalent bonding with the thiol group of Cys322, respectively. Compounds with three types of frameworks, including β-3,4-dihydroxyphenyl-, α-3,4-dihydroxybenzyl-, and α-3,4-dihydroxybenzylidene-substituted derivatives, exhibited complex and varying structure-dependent kinetics of inhibition. Among irreversible binders, methyl β-(3,4-dihydroxyphenyl)-β-(2-carboxyethyl)phosphorylpropionate was observed to be a remarkably reactive inhibitor of Sporosarcina pasteurii urease (kinact/KI = 10 420 s-1 M-1). The high potential of this group of compounds was also confirmed in Proteus mirabilis whole-cell-based inhibition assays. Some compounds followed slow-binding and reversible kinetics, e.g., methyl β-(3,4-dihydroxyphenyl)-β-phosphonopropionate, with Ki? = 0.13 μM, and an atypical low dissociation rate (residence time τ = 205 min).
New 3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one-based triazole derivatives: Design, synthesis, and biological evaluation as antiproliferative and apoptosis-inducing agents
Gaikwad, Nikhil B.,Bansode, Sapana,Biradar, Shankar,Ban, Mayuri,Srinivas, Nanduri,Godugu, Chandraiah,Yaddanapudi, Venkata M.
, (2021/08/07)
A series of 1,2,3-triazole derivatives based on the quinoline–benzimidazole hybrid scaffold was designed, synthesized, and screened against a panel of NCI-60 humanoid cancer cell lines for in vitro cytotoxicity evaluation, which revealed that compound Q6 was the most potent cytotoxic agent with excellent GI50, TGI, and LC50 values on multiple cancer cell lines. Q6 was tested further on the BT-474 breast cancer line to evaluate the mechanism of action. Preliminary screening studies based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that compound Q6 had an excellent antiproliferative effect against human breast cancer cells, BT-474, with IC50 values of 0.59 ± 0.01 μM. The detailed study based on the acridine orange/ethidium bromide staining (AO/EB) and the 4′,6-diamidino-2-phenylindole (DAPI) assay suggested that the antiproliferative activity shown was due to the induction of apoptosis on exposure to Q6. Further, DCFDA staining showed the generation of reactive oxygen species, altering the mitochondrial potential and leading to the initiation of apoptosis. This was further supported by JC-1 staining, indicating that this scaffold can contribute to the development of more potent derivatives.
Homologation of Electron-Rich Benzyl Bromide Derivatives via Diazo C-C Bond Insertion
Alegre-Requena, Juan V.,De Lescure, Louis,Modak, Atanu,Paton, Robert S.,Race, Nicholas J.,Rynders, Kathryn J.
supporting information, (2021/12/27)
The ability to manipulate C-C bonds for selective chemical transformations is challenging and represents a growing area of research. Here, we report a formal insertion of diazo compounds into the "unactivated"C-C bond of benzyl bromide derivatives catalyzed by a simple Lewis acid. The homologation reaction proceeds via the intermediacy of a phenonium ion, and the products contain benzylic quaternary centers and an alkyl bromide amenable to further derivatization. Computational analysis provides critical insight into the reaction mechanism, in particular the key selectivity-determining step.
Hydrothermal Liquefaction of α-O-4 Aryl Ether Linkages in Lignin
Lui, Matthew Y.,Chan, Bun,Yuen, Alexander K. L.,Masters, Anthony F.,Maschmeyer, Thomas
, p. 2002 - 2006 (2020/03/05)
By using lignin model compounds with relevant key characteristic structural features, the reaction pathways of α-O-4 aryl ether linkages under hydrothermal conditions are elucidated. Experimental results and computational modeling suggest that the α-O-4 linkages in lignin undergo catalyzed hydrolysis and elimination to give phenolic and alkenylbenzene derivatives as major products in subcritical water. The decreased relative permittivity of water at these high temperatures and pressures facilitates the elimination reactions. The alkyl group on the α-carbon and the methoxy groups on the phenyl rings both have positive effects on the rate of conversion of α-O-4 linkages in native lignin.
Photochemical benzylic bromination in continuous flow using BrCCl3 and its application to telescoped p-methoxybenzyl protection
Otake, Yuma,Williams, Jason D.,Rincón, Juan A.,De Frutos, Oscar,Mateos, Carlos,Kappe, C. Oliver
supporting information, p. 1384 - 1388 (2019/02/14)
BrCCl3 represents a rarely used benzylic brominating reagent with complementary reactivity to other reagents. Its reactivity has been revisited in continuous flow, revealing compatibility with electron-rich aromatic substrates. This has brought about the development of a p-methoxybenzyl bromide generator for PMB protection, which was successfully demonstrated on a pharmaceutically relevant intermediate on 11 g scale, giving 91% yield and a PMB-Br space-time-yield of 1.27 kg L?1 h?1
Nitrogen-containing heterocycle derivatives and applications thereof
-
Paragraph 0171; 0172, (2018/03/24)
The invention discloses nitrogen-containing heterocycle derivatives and applications thereof, relates to compounds of a general formula (V), a preparing method thereof and applications of the compounds in medicines, and more particularly relates to compound derivatives of compounds shown as the general formula (V), a preparing method thereof and uses of the derivatives in medicines preventing andtreating hyperlipemia, hypercholesterolemia, hypertriglyceridemia, fatty degeneration of liver, diabetes mellitus type 2, hyperglycemia, obesity or insulin resistance and metabolic syndrome and resisting antitumor, with the derivatives being adopted as therapeutic agents. The compounds disclosed by the invention can also reduce total cholesterol, LDL-cholesterol and triglyceride, can increase liver LDL receptor expression, and inhibit PCSK9 expression.
Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors
Li, Ning,Wang, Li-Jun,Jiang, Bo,Guo, Shu-Ju,Li, Xiang-Qian,Chen, Xue-Chun,Luo, Jiao,Li, Chao,Wang, Yi,Shi, Da-Yong
supporting information, p. 2131 - 2135 (2018/05/25)
A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC50 values of 64.47 nM, 188.7 nM and 65.36 nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure–activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes.
Discovery of boron-containing compounds as Aβ aggregation inhibitors and antioxidants for the treatment of Alzheimer's disease
Lu, Chuan-Jun,Hu, Jinhui,Wang, Zechen,Xie, Shishun,Pan, Tingting,Huang, Ling,Li, Xingshu
, p. 1862 - 1870 (2018/11/24)
A novel series of boron-containing compounds were designed, synthesized and evaluated as multi-target-directed ligands against Alzheimer's disease. The biological activity results demonstrated that these compounds possessed a significant ability to inhibit self-induced Aβ aggregation (20.5-82.8%, 20 μM) and to act as potential antioxidants (oxygen radical absorbance capacity assay using fluorescein (ORAC-FL) values of 2.70-5.87). In particular, compound 17h is a potential lead compound for AD therapy (IC50 = 3.41 μM for self-induced Aβ aggregation; ORAC-FL value = 4.55). Compound 17h also functions as a metal chelator. These results indicated that boron-containing compounds could be new structural scaffolds for the treatment of AD.
Synthesis of (+)-salvianolic acid A from sodium Danshensu
Xu, Kai,Liu, Hao,Liu, Delong,Sheng, Cheng,Shen, Jiefeng,Zhang, Wanbin
supporting information, p. 5996 - 6002 (2018/09/06)
(+)-Salvianolic acid A, one of the most active components in the traditional Chinese medicine Danshen, has been synthesized over 10 steps in 6.5% overall yield. Starting from inexpensive ortho-vanillin and sodium Danshensu (synthesized via asymmetric catalysis in our group), the process consists of the following: A Wittig reaction that gives the desire product with absolute E-configuration, a demethylation reaction with AlCl3 in a satisfactory yield, and a practical deprotection of allylic groups to afford the terminal product (+)-salvianolic acid A. The current synthetic technology possesses the advantages of using inexpensive starting materials, mild reaction conditions and has the potential for use in large scale synthesis.
