40918-96-5Relevant academic research and scientific papers
Scalable Synthesis and Cancer Cell Cytotoxicity of Rooperol and Analogues
Bjornstal, Olaf T.,Du, Liqin,Jemal, Mauricio A.,Kerwin, Sean M.,Lee, Dallas,Rodebaugh, Mary,Schwartz, Zachary T.,Shelton, Spencer D.,Theisen, Peter D.,Zhao, Zhenze
, (2022/03/23)
Plant polyphenols, such as the African potato (Hypoxis hemerocallidea)-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues. While none of the analogues examined here were superior to rooperol in preventing the growth of cancer cells, analogues containing phenol or methylenedioxyphenyl replacements for one or both catechol rings were nearly as effective as rooperol.
Design, synthesis and antibacterial activity against pathogenic mycobacteria of conjugated hydroxamic acids, hydrazides and O-alkyl/O-acyl protected hydroxamic derivatives
Canaan, Stéphane,Cavalier, Jean-Fran?ois,Magrioti, Victoria,Mallick, Ivy,Mavrikaki, Vasiliki,Pagonis, Alexandros,Poncin, Isabelle
supporting information, (2022/03/27)
With the aim to discover new antituberculous molecules, three novel series of 23 hydroxamic acids, 13 hydrazides, and 9O-alkyl/O-acyl protected hydroxamic acid derivatives have been synthesized, and fully characterized by spectral 1H NMR,
Oxoammonium-Mediated Allylsilane–Ether Coupling Reaction
Carlet, Federica,Bertarini, Greta,Broggini, Gianluigi,Pradal, Alexandre,Poli, Giovanni
supporting information, p. 2162 - 2168 (2021/04/02)
A new C(sp3)?H functionalization reaction consisting of the oxidative α-allylation of allyl- and benzyl- methyl ethers has been developed. The C?C coupling could be carried out under mild conditions thanks to the use of cheap and green oxoammonium salts. The scope of the reaction was studied over 27 examples, considering the nature of the substituents on the two coupling partners.
Dramatic Effect of γ-Heteroatom Dienolate Substituents on Counterion Assisted Asymmetric Anionic Amino-Cope Reaction Cascades
Das, Pradipta,Delost, Michael D.,Qureshi, Munaum H.,Bao, Jianhua,Fell, Jason S.,Houk, Kendall N.,Njardarson, Jon T.
supporting information, p. 5793 - 5804 (2021/05/07)
We report a dramatic effect on product outcomes of the lithium ion enabled amino-Cope-like anionic asymmetric cascade when different γ-dienolate heteroatom substituents are employed. For dienolates with azide, thiomethyl, and trifluoromethylthiol substituents, a Mannich/amino-Cope/cyclization cascade ensues to form chiral cyclohexenone products with two new stereocenters in an anti-relationship. For fluoride-substituted nucleophiles, a Mannich/amino-Cope cascade proceeds to afford chiral acyclic products with two new stereocenters in a syn-relationship. Bromide- and chloride-substituted nucleophiles appear to proceed via the same pathway as the fluoride albeit with the added twist of a 3-exo-trig cyclization to yield chiral cyclopropane products with three stereocenters. When this same class of nucleophiles is substituted with a γ-nitro group, the Mannich-initiated cascade is now diverted to a β-lactam product instead of the amino-Cope pathway. These anionic asymmetric cascades are solvent- and counterion-dependent, with a lithium counterion being essential in combination with etheral solvents such as MTBE and CPME. By altering the geometry of the imine double bond from E to Z, the configurations at the R1 and X stereocenters are flipped. Mechanistic, computational, substituent, and counterion studies suggest that these cascades proceed via a common Mannich-product intermediate, which then proceeds via either a chair (X = N3, SMe, or SCF3) or boat-like (X = F, Cl, or Br) transition state to afford amino-Cope-like products or β-lactam in the case of X = NO2.
Mizoroki-Heck Reaction of Unstrained Aryl Ketones via Ligand-Promoted C-C Bond Olefination
Wang, Mei-Ling,Xu, Hui,Li, Han-Yuan,Ma, Biao,Wang, Zhen-Yu,Wang, Xing,Dai, Hui-Xiong
supporting information, p. 2147 - 2152 (2021/04/05)
Mizoroki-Heck reaction of unstrained aryl ketone with acrylate/styrene is accomplished via palladium-catalyzed ligand-promoted C-C bond cleavage. Various (hetero)aryl ketones are compatible in the reaction, affording the alkene product in good to excellent yields. Further applications in the late-stage olefination of some drugs, natural products, and fragrance-derived aryl ketones demonstrate the synthetic utility of this protocol. By employing ketone as both the directing group and the leaving group, 1,2-bifunctionalization is achieved via sequential ortho-C-H alkylation/ipso-Heck olefination.
Design, synthesis, trypanocidal activity, and studies on human albumin interaction of novel s-alkyl-1,2,4-triazoles
Franklim, Tatiany N.,Freire-De-Lima, Leonardo,Chaves, Otávio A.,LaRocque-De-Freitas, Isabel F.,da Silva-Trindade, Joana D.,Netto-Ferreira, José C.,Freire-De-Lima, Célio G.,Decoté-Ricardo, Debora,Previato, José O.,Mendon?a-Previato, Lucia,De Lima, Marco E.F.
, p. 1378 - 1394 (2019/08/26)
Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 μmol L-1, respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream.
Synthesis of Analogs of Trans-Fagaramide and Their Cytotoxic Activity
Tomas, Melissa Barrera,Shiao, Tze Chieh,Nguyen, Phuong Trang,Bourgault, Steve,Roy, René
, p. 995 - 1004 (2018/02/22)
A series of 30 compounds were synthetized inspired by active trans-fagaramide structure skeleton. On this synthetic platform, 18 compounds were achieved via Knoevenagel condensation using maleic acid and piperonal, followed by peptide coupling with various amines, giving an average yield of 54%. Subsequently, nine compounds were obtained by palladium-mediated Heck coupling with an average yield of 79%. In addition, cytotoxic activity was evaluated against cardiomyoblast H9c2, breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2, and glioblastoma U-87 cells. The results revealed two aryl halogen-substituted compounds moderately active against H9c2 and MCF7 with IC50 values > 50 μM. One functionalized coumarin showed inhibitory activity against H9c2 (IC50 > 50 μM). In contrast, p-aminophenyl-β-monosubstituted trans-fagaramide was found to inhibit MCF7 (IC50 > 50 μM) without showing toxicity against H9c2 cells.
The Catalytic Asymmetric Mukaiyama–Michael Reaction of Silyl Ketene Acetals with α,β-Unsaturated Methyl Esters
Gatzenmeier, Tim,Kaib, Philip S. J.,Lingnau, Julia B.,Goddard, Richard,List, Benjamin
supporting information, p. 2464 - 2468 (2018/02/06)
α,β-Unsaturated esters are readily available but challenging substrates to activate in asymmetric catalysis. We now describe an efficient, general, and highly enantioselective Mukaiyama–Michael reaction of silyl ketene acetals with α,β-unsaturated methyl esters that is catalyzed by a silylium imidodiphosphorimidate (IDPi) Lewis acid.
Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin
Saavedra, Diana I.,Rencher, Benjamin D.,Kwon, Doo-Hyun,Smith, Stacey J.,Ess, Daniel H.,Andrus, Merritt B.
, p. 2018 - 2026 (2018/02/23)
Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic de
Transition-Metal-Free Stereocomplementary Cross-Coupling of Diols with Boronic Acids as Nucleophiles
Ortega, Víctor,Del Castillo, Estefanía,Csák?, Aurelio G.
supporting information, p. 6236 - 6239 (2017/11/24)
The transition-metal-free diastereoselective C(sp2)-C(sp3) cross-coupling between unprotected diols and boronic acids or potassium organotrifluoroborates is reported. Depending on the reaction conditions, the syn or the anti reaction products are obtained in a stereocomplementary fashion. This type of coupling is developed with alkenyl-, heteroaryl- and arylboron compounds as carbon nucleophiles.
