6413-10-1Relevant articles and documents
Synthesis, activity and mechanism for double-ring conjugated enones
Chen, Guangying,Huang, Gangliang,Liu, Jian,Zhou, Shiyang
, (2021)
The relationship between TLR4 and inflammation-related diseases has been paid more and more attention. The studies have shown that TLR4/NF-κB signaling pathway plays an important role in the transmission of inflammatory signals. A large number of pro-inflammatory factors, chemokines, adhesion factors, TLR4 and its ligands interact with each other, and jointly promote the development of diseases. In this work, 8 target compounds were synthesized to screen the inhibitory activity of TLR4 in vitro. The results of TLR4 inhibition test in vitro showed that the double-ring conjugated enones had a good inhibitory activity, and the IC50 value of compound 4f was 0.56 ± 0.10 μM, and it was superior to the positive control methotrexate. To further study the anti-inflammatory effect and mechanism of double-ring conjugated enones by using LPS induced rat synovial cell inflammation model. The results of the mechanism test showed that compound 4f could effectively promote the apoptosis of rat synovial cells, and the mechanism might be related to the up-regulation of the expression of apoptosis-related protein Caspase-3. In addition, compound 4f could significantly inhibit the increase of inflammatory factors TNF-α, IL-1β and IL-6 in rat synovial cells induced by LPS, showing a good anti-inflammatory activity. In the TLR4/NF-κB signaling pathway test of rat synovial cells, compound 4f can effectively regulate the expression levels of TLR4, MyD88, NF-κB and IκB related proteins in TLR4/NF-κB signaling pathway, which may be due to its inhibition of LPS-induced inflammation in rat synovial cells. At the same time, it inhibits the abnormal proliferation of cells and its important mechanism promoted of apoptosis.
Efficient and straightforward preparation of a building block for (-)-teubrevin G synthesis via chemically diversed oriented synthesis
Velazquez, Daniel Garcia,Luque, Rafael
, p. 7004 - 7007 (2011)
A rapid and efficient methodology to highly functionalised molecular units well suited as scaffolds for diversity-oriented molecular construction in the synthesis of natural products is reported herein. A key macrocyclic intermediate in the synthesis of the neo-clerodane diterpene (-)-teubrevin G was successfully synthesized in a 5-step sequence in a 70% overall yield using a novel intramolecular coupling between an allylborating agent and a 1,5-dialdehyde moiety.
Design, synthesis and anti-rheumatoid arthritis evaluation of double-ring conjugated enones
Zhou, Shiyang,Zou, Huiying,Huang, Gangliang,Chen, Guangying,Zhou, Xueming,Huang, Shuheng
, (2021/02/22)
Four series of double-ring conjugated enones were designed, synthesized and studied for the inhibition of synovial cell activity through the modification of Dysodensiol K core structure, double-ring, double-bond and double-carbonyl groups. For in vitro synovial cell assay of rats, compound 151 and 168 exhibited good inhibitory activities, with IC50 values of 2.71 ± 0.18 and 2.68 ± 0.16 μM respectively. At the same time, the LDH release and LD50 test results revealed that the target compounds were low cytotoxicity and acute toxicity. For in vivo CIA model test through the oral administration, compounds 151 and 168 were exhibited similar effect to positive control group methotrexate.
Preparation of pyridine derivatives from the corresponding 5-acetal-1-carbonyl compounds by acid promoted cyclization
Konno, Hiroyuki,Mihara, Hiromichi,Watanabe, Yuki
, p. 1314 - 1329 (2021/07/19)
The synthesis of four alkylpyridine derivatives from 5-acetal-1-carbonyl compounds via the one-pot, acid-promoted cyclization of oxime intermediates is described. In addition, a dihydroxypyridine and pyridinium salt were also synthesized. The pyridine formation step was not affected by the stereochemistry of the precursors used.
Br?nsted acidic cellulose-PO3H: An efficient catalyst for the chemoselective synthesis of fructones and trans-esterification via condensation of acetoacetic esters with alcohols and diols
Naikwadi, Dhanaji R.,Singh, Amravati S.,Biradar, Ankush V.
, (2021/10/04)
Cellulose is the most abundant organic source and has expedient a great deal of interest as renewable and emerged as sustainable feedstock. The functionalization of cellulose as designed catalytic system intriguing furnished to the production of fine chemicals. Herein, we synthesized an environmental friendly solid acid catalyst by functionalizing cellulose with phosphoric acid (PO3H). The successful functionalization of cellulose with PO3H was confirmed by 31P NMR, ICP-OES, FE-SEM, and XPS analysis. ICP-OES revealed the presence of phosphorus content of ～1.0 wt. % on the catalyst's surface while elemental mapping by FESEM and XPS shows a uniform distribution of phosphorus over the material. The synthesized solid acid catalyst was utilized for condensation of diols with acetoacetic esters in solvent-free conditions to synthesize fine chemicals. The present approach not only circumvented the one-step protection and other products but more fascinatingly provided trans-esterification of acetoacetic esters with diols and n-alcohols. The catalyst was successfully used for chemoselective protection on ethyl acetoacetate with 1, 2 diols to essential fructone molecule with ～100% conversion and 99% selectivity. The results suggested that the catalyst has the advantage over commercial solid acid heterogeneous and homogeneous catalysts.
Synthetic method of fructone compound
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Paragraph 0036-0038; 0045-0047; 0057-0059; 0060-0069, (2020/07/13)
The invention discloses a synthetic method of a fructone compound, and relates to the technical field of chemical synthesis. The synthetic method comprises the following step that a beta-keto ester compound reacts with a diol compound in the presence of an acidic cation exchange resin catalyst to generate a fructone compound. According to the synthetic method of the fructone compound, the acid cation exchange resin is adopted as the catalyst, the catalyst can be repeatedly used, catalysis is efficient, and selectivity is high.
Total synthesis and anti-inflammatory evaluation of violacin A and its analogues
Liu, Qingyin,Mu, Yu,An, Qi,Xun, Jiali,Ma, Jian,Wu, Wenxi,Xu, Minjuan,Xu, Jun,Han, Li,Huang, Xueshi
, (2019/11/26)
A concise total synthesis of an exceedingly potent anti-inflammatory agent violacin A as well as the preparation of thirty analogues of this lead from commercially available orcinol are described. Highlights of our synthetic efforts involve Friedel-Crafts acylation, the regioselective etherification and esterification of phenolic hydroxyl groups, and Baker-Venkatamaran rearrangement to form basic skeleton of violacin A. The deprotection reaction with Pd-catalytic was involved to avoid the elimination of the hemiacetal hydroxyl at C2. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO) production using lipopolysaccharide (LPS)-induced Raw264.7 cells. A range of violacin A derivatives 11b, 11d, 11f, 12e, 12g, 13g, 17d-g exhibited stronger anti-inflammatory effect than that of violacin A. Notably, halogeno-benzyloxy substituent at C-7 were favourable for anti-inflammatory activities of violacin A derivatives. Additionally, Western blot results indicated halogeno-benzyloxy derivatives inhibited pro-inflammatory cytokines releases correlated with the suppression of NF-κB signaling pathway.
Unique photoaffinity probes to study TGFβ signaling and receptor fates
L?ngle,Wesseler,Fl?tgen,Leek,Plowright,Schade
supporting information, p. 4323 - 4326 (2019/04/26)
A novel synthetic approach is used to prepare a diverse set of "first-in-class" dihydropyridine-based TGFβ receptor degraders bearing photoaffinity labels. These probes serve as valuable tools to study TGFβ receptor fates and dynamics-an important challenge in chemical biology.
COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS
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Paragraph 00104, (2018/04/20)
The present invention relates to novel compounds and their use in the prophylactic and/or therapeutic treatment of hypertension and/or fibrosis.
Design, synthesis and biological evaluation of multifunctional tacrine-curcumin hybrids as new cholinesterase inhibitors with metal ions-chelating and neuroprotective property
Liu, Zhikun,Fang, Lei,Zhang, Huan,Gou, Shaohua,Chen, Li
, p. 2387 - 2398 (2017/04/03)
Total sixteen tacrine-curcumin hybrid compounds were designed and synthesized for the purpose of searching for multifunctional anti-Alzheimer agents. In vitro studies showed that these hybrid compounds showed good cholinesterase inhibitory activity. Particularly, the potency of K3-2 is even beyond tacrine. Some of the compounds exhibited different selectivity on acetylcholinesterase or butyrylcholinesterase due to the structural difference. Thus, the structure and activity relationship is summarized and further discussed based on molecular modeling studies. The ORAC and MTT assays indicated that the hybrid compounds possessed pronounced antioxidant activity and could effectively protect PC12 cells from the H2O2/Aβ42-induced toxicity. Moreover, the hybrid compounds also showed positive metal ions-chelating ability in vitro, suggesting a potential to halt ion-induced Aβ aggregation. All the obtained results demonstrated that the tacrine-curcumin hybrid compounds, in particular compound K3-2, can be considered as potential therapeutic agents for Alzheimer's disease.
