19676-64-3Relevant academic research and scientific papers
A short synthesis of (±)-antroquinonol in an unusual scaffold of 4-hydroxy-2-cyclohexenone
Hsu, Che-Sheng,Chou, Ho-Hsuan,Fang, Jim-Min
, p. 5510 - 5519 (2015)
Antroquinonol, which was first isolated from a mushroom, Antrodia cinnamomea, found in Taiwan, is an anticancer compound with a unique core structure of 4-hydroxy-2,3-dimethoxycyclohex-2-enone carrying methyl, farnesyl and hydroxyl substituents in the 4,5-cis-5,6-trans configuration. A short synthesis of (±)-antroquinonol is accomplished in seven steps from 2,3,4-trimethoxyphenol, which is oxidized in methanol to a highly electron-rich substrate of 2,3,4,4-tetramethoxycyclohexadienone and then a Michael reaction with dimethylcuprate is performed as the key step, followed by alkylation, reduction and epimerization to incorporate the required substituents at three contiguous stereocenters.
Differing selectivities in mechanochemical versus conventional solution oxidation using Oxone
Collom,Anastas,Beach,Crabtree,Hazari,Sommer
, p. 2344 - 2347 (2013)
A mechanochemical oxidation of methoxylated aromatic chemicals is described, providing an example of a very different selectivity as compared to solution-based chemistry. Oxone was shown to react with 1,2,3-trimethoxybenzene to yield predominantly 2,6-dimethoxybenzoquinone in the solid state or 2,3,4-trimethoxyphenol in solution. The difference in effective acidity of the reaction conditions was not apparently responsible for the observed selectivity. The mechanochemical method described is simple, reproducible, and gave higher yield at higher conversion of substrate compared to solution conditions.
Studies toward the development of antiproliferative neoclerodanes from salvinorin A
Vasiljevik, Tamara,Groer, Chad E.,Lehner, Kurt,Navarro, Hernan,Prisinzano, Thomas E.
, p. 1817 - 1824 (2014)
The success rate for central nervous system (CNS) drug candidates in the clinic is relatively low compared to the industry average across other therapeutic areas. Penetration through the blood-brain barrier (BBB) to reach the therapeutic target is a major obstacle in development. The rapid CNS penetration of salvinorin A has suggested that the neoclerodane nucleus offers an excellent scaffold for developing antiproliferative compounds that enter the CNS. The Liebeskind-Srogl reaction was used as the main carbon-carbon bond-forming step toward the synthesis of quinone-containing salvinorin A analogues. Quinone-containing salvinorin A analogues were shown to have antiproliferative activity against the MCF7 breast cancer cell line, but show no significant activity at the κ-opioid receptors. In an in vitro model of BBB penetration, quinone-containing salvinorin A analogues were shown to passively diffuse across the cell monolayer. The analogues, however, are substrates of P-glycoprotein, and thus further modification of the molecules is needed to reduce the affinity for the efflux transporter.
An alternative route for the synthesis of 2,3,4,5-tetramethoxytoluene
Vera, William J.,Chinea, Kimberly,Banerjee, Ajoy K.
, p. 186 - 187 (2009)
The transformation of the commercially available 2,3,4- trimetho×ybenzaldehyde to 2,3,4,5-tetrametho×ytoluene using a Dakin reaction to insert the extra oxygen, formylation, reduction and methylation of the phenolic hydro×yl group is described.
Total Synthesis of Dactylicapnosines A and B
Zhao, Yinjiao,Li, Yuda,Wang, Bei,Zhao, Jingfeng,Li, Liang,Luo, Xiao-Dong,Zhang, Hongbin
, p. 13772 - 13778 (2020)
Dactylicapnosines A and B, two natural products from Dactylicapnos scandens, exhibited potent anti-inflammatory and analgesic activities both in vitro and in vivo. In this paper, we report our second-generation synthesis of dactylicapnosine A and the first total synthesis of dactylicapnosine B. Our synthetic route features acid-induced isomerization of o-quinone (16), Co-mediated regioselective ring contraction of p-quinone (8b), and oxidative methoxylation of enone (18). This modified sequence provides dactylicapnosine A in 14 steps with an overall yield of 12% from a known compound (14a) and also offers opportunities to synthesize dactylicapnosine-like analogues for biological investigations.
Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
Chen, Yuwen,Huang, Yulan,Jiao, Wei,Li, Fu,Li, Suiyan,Li, Wenhua,Lin, Yuan,Liu, Wanli,Ma, Yuling,Sheng, Yuwen,Suksamrarn, Apichart,Wang, Fei,Wang, Jing,Wei, Xiao,Wisanwattana, Wisanee,Wu, Wenbi,Zeng, Zhongqiu,Zhang, Guolin,Zhang, Jichao,Zhu, Qiyu
, (2022/01/03)
Cancer cell proliferation in some organs often depends on conversion of pyruvate to oxaloacetate via pyruvate carboxylase (PC) for replenishing the tricarboxylic acid cycle to support biomass production. In this study, PC was identified as the cellular target of erianin using the photoaffinity labeling-click chemistry-based probe strategy. Erianin potently inhibited the enzymatic activity of PC, which mediated the anticancer effect of erianin in human hepatocellular carcinoma (HCC). Erianin modulated cancer-related gene expression and induced changes in metabolic intermediates. Moreover, erianin promotes mitochondrial oxidative stress and inhibits glycolysis, leading to insufficient energy required for cell proliferation. Analysis of 14 natural analogs of erianin showed that some compounds exhibited potent inhibitory effects on PC. These results suggest that PC is a cellular target of erianin and reveal the unrecognized function of PC in HCC tumorigenesis; erianin along with its analogs warrants further development as a novel therapeutic strategy for the treatment of HCC.
Practical Synthesis of Polymethylated Flavones: Nobiletin and Its Desmethyl Derivatives
Asakawa, Tomohiro,Sagara, Hiroto,Kanakogi, Masaki,Hiza, Aiki,Tsukaguchi, Yuta,Ogawa, Takahiro,Nakayama, Miho,Ouchi, Hitoshi,Inai, Makoto,Kan, Toshiyuki
, p. 595 - 602 (2019/04/01)
We present a practical synthesis of the polymethoxylated citrus flavone nobiletin that is suitable for use on a hundred gram scale. Ready availability of this compound and its derivatives will aid detailed chemical-biological investigations of their biological activities, including activation of signaling via the cAMP-dependent protein kinase A/extracellular signal-related protein kinase/cAMP response element-binding protein pathway.
Rational design, synthesis and biological evaluation of ubiquinone derivatives as IDO1 inhibitors
Ding, Yuyang,Tang, Fei,Xue, Xiaoqian,Luo, Jinfeng,Hussain, Muzammal,Huang, Yanhui,Wang, Zhen,Jiang, Hao,Tu, Zhengchao,Zhang, Jiancun
supporting information, (2019/05/21)
Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive therapeutic target for the treatment of cancer, chronic viral infections and neurological disorders characterized by pathological immune stimulation. Herein, a series of known metal-chelating ubiquinone derivatives were designed, synthesized and evaluated for the IDO1 inhibiting activities. The docking studies showed that the compounds 11, 16, 18 and coenzyme-Q1 exhibited different binding modes to IDO1 protein. Among these compounds, the most active compound is 16d with an IC50 of 0.13 μM in enzymatic assay. The results reveal that a possible halogen bonding interaction between the bromine atom (3-Br) and Cys129 significantly enhances the inhibition activity against IDO1. This study provides structural insights of the interactions between ubiquinone analogues and IDO1 protein for the further modification and optimization.
Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study
Bai, Yajun,He, Xirui,Bai, Yujun,Sun, Ying,Zhao, Zefeng,Chen, Xufei,Li, Bin,Xie, Jing,Li, Yang,Jia, Pu,Meng, Xue,Zhao, Ye,Ding, Yanrui,Xiao, Chaoni,Wang, Shixiang,Yu, Jie,Liao, Sha,Zhang, Yajun,Zhu, Zhiling,Zhang, Qiang,Zhao, Yuhui,Qin, Fanggang,Zhang, Yi,Wei, Xiaoyang,Zeng, Min,Liang, Jing,Cuan, Ye,Shan, Guangzhi,Fan, Tai-Ping,Wu, Biao,Zheng, Xiaohui
, (2019/09/18)
Inspired by the traditional Chinese herbal pair of Polygala tenuifolia-Acori Tatarinowii for treating epilepsy, 33 novel substituted cinnamic α-asaronol esters and analogues were designed by Combination of Traditional Chinese Medicine Molecular Chemistry (CTCMMC) strategy, synthesized and tested systematically not only for anticonvulsant activity in three mouse models but also for LDH inhibitory activity. Thereinto, 68–70 and 75 displayed excellent and broad spectra of anticonvulsant activities with modest ability in preventing neuropathic pain, as well as low neurotoxicity. The protective indices of these four compounds compared favorably with stiripentol, lacosamide, carbamazepine and valproic acid. 68–70 exhibited good LDH1 and LDH5 inhibitory activities with noncompetitive inhibition type, and were more potent than stiripentol. Notably, 70, as a representative agent, was also shown as a moderately positive allosteric modulator at human α1β2γ2 GABAA receptors (EC50 46.3 ± 7.3 μM). Thus, 68–70 were promising candidates for developing into anti-epileptic drugs, especially for treatment of refractory epilepsies such as Dravet syndrome.
Synthesis of isoflavones by tandem demethylation and ring-opening/cyclization of methoxybenzoylbenzofurans
Kunyane, Phaladi,Sonopo, Molahlehi S.,Selepe, Mamoalosi A.
supporting information, p. 3074 - 3082 (2019/11/19)
The unexpected conversion of benzoylbenzofurans into isoflavones through an intramolecular cascade that involves deprotection and ring-opening/cyclization is described. This was discovered in an investigation of the possible transformation of benzoylbenzofurans into coumaronochromones. This route affords isoflavones in two major steps from acetophenones and benzoquinones. The transformation was validated by synthesizing differently substituted isoflavone derivatives and further applied to a concise synthesis of a potential anticancer lead compound, glaziovianin A (1).
