623-05-2Relevant articles and documents
Acute toxicity of benzoic acids to the crustacean Daphnia magna
Kamaya, Yasushi,Fukaya, Yuki,Suzuki, Kyoji
, p. 255 - 261 (2005)
The acute immobilization toxicity of benzoic acids substituted with hydroxyl and/or methoxyl groups on the aromatic ring was determined for the freshwater crustacean Daphnia magna under neutralized condition (initial pH: 7.45 ± 0.05). Toxicity, expressed as EC50 value, varied depending largely on the number and position of phenolic hydroxyl groups. Especially, benzoic acids with ortho-substituted hydroxyl groups were more toxic than benzoic acids with meta- and/or para-substituted hydroxyl groups. Whereas the limited data indicated that methoxyl substitution had relatively small and variable effects on the toxicity. Of the tested compounds, 2,4,6- trihydroxybenzoic acid showed the highest toxicity with the 48 h EC50 of 10 μmol l-1. This was 700 times as toxic as the parent benzoic acid (48 h EC50 = 7.0 mmol l-1) and about two orders of magnitude higher than those previously reported for monohalogenated benzoic acid derivatives in Daphnia. Within the subgroups based on the number of hydroxyl groups (NOH), the toxicity variations due to the position of hydroxyl groups appeared to be correlated with the logarithms of n-octanol/water partition coefficients (log Pow). The toxicity of benzoic acids existing almost entirely as their ionized forms could be expressed as simple structure-toxicity relationships using these two descriptors (NOH and log Pow).
Selective Synthesis of 4-Hydroxymethylphenol catalysed by Cyclodextrins having Hydroxypropyl Residues
Komiyama, Makoto
, p. 651 - 652 (1988)
The selective synthesis of 4-hydroxymethylphenol from phenol and formaldehyde has been achieved using α-, β-, and γ-cyclodextrins having 2-hydroxypropyl residues.
Determining Factors for the Product Para/Ortho Ratio and Reaction Rate in the Formation of (Hydroxymethyl)phenols from Phenol and Formaldehyde
Komiyama, Makoto
, p. 2079 - 2082 (1988)
Formations of 2- and 4-(hydroxymethyl)phenols from phenol and formaldehyde in aqueous alkaline solutions were kinetically investigated by the use of HPLC.The para/ortho ratio for the products sigmoidally increased with increasing concentration of sodium hydroxide, whereas the total yield of the (hydroxymethyl)phenols showed a steep maximum at the charged molar ratio unity of sodium hydroxide to phenol.Use of lithium hydroxide and potassium hydroxide, in place of sodium hydroxide, as alkaline catalysts results in almost the same para/ortho ratios.The addition of potassium chloride and magnesium sulfate decreased both the para/ortho ratio and the yield.These results indicate that the reactions proceed via an electrophilic attack of formaldehyde, which is free from the adduct formation with hydroxide ion, at phenolate ion.Electrostatic interactions between the phenoxide oxygen atom of the phenol and the incoming hydroxymethyl residues in the transition state exhibit a predominant role in the determination of the para/ortho ratio.
Discovery of new and highly effective quadruple FFA1 and PPARα/γ/δ agonists as potential anti-fatty liver agents
Cai, Zongyu,Deng, Liming,Geng, Xinqian,Hu, Lijun,Jiao, Shixuan,Li, Zheng,Ren, Qiang,Wang, Bin,Yang, Ying,Zhang, Luyong,Zhou, Zongtao
supporting information, (2021/12/27)
Non-alcoholic fatty liver disease (NAFLD) has become the most common hepatic disease, while no drug was approved until now. The previous study reported that the quadruple FFA1/PPAR-α/γ/δ agonist RLA8 provided better efficacy than obeticholic acid on NASH. In the present study, two design strategies were introduced to explore better quadruple FFA1/PPAR-α/γ/δ agonists with improved metabolic stability. These efforts ultimately resulted in the identification of ZLY18, a quadruple FFA1/PPAR-α/γ/δ agonist with twice higher metabolic half-life than RLA8 in the liver microsome. In the triton-1339W-induced hyperlipidemic model, ZLY18 reversed hyperlipidemia to an almost normal level, which exhibited far stronger lipid-lowering effects than that of RLA8. Moreover, ZLY18 significantly decreased steatosis, hepatocellular ballooning, inflammation and liver fibrosis in NASH model even better than RLA8. Further mechanism studies suggested that ZLY18 exerts stronger effects than RLA8 on the regulation of the gene related to lipid synthesis, oxidative stress, inflammation and fibrosis. In addition, ZLY18 is more effective than pirfenidone in the prevention of CCl4-induced liver fibrosis. Besides, ZLY18 has an acceptable safety profile in the acute toxicity study at a high dose of 500 mg/kg. Therefore, ZLY18 represents a novel and highly promising quadruple FFA1/PPAR-α/γ/δ agonist worth of further investigation and development.
Rapid biosynthesis of phenolic glycosides and their derivatives from biomass-derived hydroxycinnamates
Zhao, Mingtao,Hong, Xulin,Abdullah,Yao, Ruilian,Xiao, Yi
supporting information, p. 838 - 847 (2021/02/09)
Biomass-derived hydroxycinnamates (mainly includingp-coumaric acid and ferulic acid), which are natural sources of aromatic compounds, are highly underutilized resources. There is a need to upgrade them to make them economically feasible. Value-added phenolic glycosides and their derivatives, both belonging to a class of plant aromatic natural products, are widely used in the nutraceutical, pharmaceutical, and cosmetic industries. However, their complex aromatic structures make their efficient biosynthesis a challenging process. To overcome this issue, we created three novel synthetic cascades for the biosynthesis of phenolic glycosides (gastrodin, arbutin, and salidroside) and their derivatives (hydroquinone, tyrosol, hydroxytyrosol, and homovanillyl alcohol) fromp-coumaric acid and ferulic acid. Moreover, because the biomass-derived hydroxycinnamates directly provided aromatic units, the cascades enabled efficient biosynthesis. We achieved substantially high production rates (up to or above 100-fold enhancement) relative to the glucose-based biosynthesis. Given the ubiquity of the aromatic structure in natural products, the use of biomass-derived aromatics should facilitate the rapid biosynthesis of numerous aromatic natural products.
Ligand compound for copper catalyzed aryl halide coupling reaction, catalytic system and coupling reaction
-
Paragraph 0152-0159, (2021/05/29)
The invention provides a ligand compound capable of being used for copper catalyzed aryl halide coupling reaction, the ligand compound is a three-class compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group, and the invention also provides a catalytic system for the aryl halide coupling reaction. Thecatalytic system comprises a copper catalyst, a compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group adopted as a ligand, alkali and a solvent, and meanwhile, the invention also provides a system for the aryl halide coupling reaction adopting the catalyst system. The compound containing the 2-(substituted or non-substituted) aminopyridine nitrogen oxygen group can be used as the ligand for the copper catalyzed aryl chloride coupling reaction, and the ligand is stable under a strong alkaline condition and can well maintain catalytic activity when being used for the copper-catalyzed aryl chloride coupling reaction. In addition, the copper catalyst adopting the compound as the ligand can particularly effectively promote coupling of copper catalyzed aryl chloride and various nucleophilic reagents which are difficult to generate under conventional conditions, C-N, C-O and C-S bonds are generated, and numerous useful small molecule compounds are synthesized. Therefore, the aryl halide coupling reaction has a very good large-scale application prospect by adopting the copper catalysis system of the ligand.
Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)
Linciano, Pasquale,Benedetti, Rosaria,Pinzi, Luca,Russo, Fabiana,Chianese, Ugo,Sorbi, Claudia,Altucci, Lucia,Rastelli, Giulio,Brasili, Livio,Franchini, Silvia
, (2020/11/24)
Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.
Hydroboration Reaction and Mechanism of Carboxylic Acids using NaNH2(BH3)2, a Hydroboration Reagent with Reducing Capability between NaBH4and LiAlH4
Wang, Jin,Ju, Ming-Yue,Wang, Xinghua,Ma, Yan-Na,Wei, Donghui,Chen, Xuenian
, p. 5305 - 5316 (2021/04/12)
Hydroboration reactions of carboxylic acids using sodium aminodiboranate (NaNH2[BH3]2, NaADBH) to form primary alcohols were systematically investigated, and the reduction mechanism was elucidated experimentally and computationally. The transfer of hydride ions from B atoms to C atoms, the key step in the mechanism, was theoretically illustrated and supported by experimental results. The intermediates of NH2B2H5, PhCH= CHCOOBH2NH2BH3-, PhCH= CHCH2OBO, and the byproducts of BH4-, NH2BH2, and NH2BH3- were identified and characterized by 11B and 1H NMR. The reducing capacity of NaADBH was found between that of NaBH4 and LiAlH4. We have thus found that NaADBH is a promising reducing agent for hydroboration because of its stability and easy handling. These reactions exhibit excellent yields and good selectivity, therefore providing alternative synthetic approaches for the conversion of carboxylic acids to primary alcohols with a wide range of functional group tolerance.
Ambient-pressure highly active hydrogenation of ketones and aldehydes catalyzed by a metal-ligand bifunctional iridium catalyst under base-free conditions in water
Wang, Rongzhou,Yue, Yuancheng,Qi, Jipeng,Liu, Shiyuan,Song, Ao,Zhuo, Shuping,Xing, Ling-Bao
, p. 1 - 7 (2021/05/17)
A green, efficient, and high active catalytic system for the hydrogenation of ketones and aldehydes to produce corresponding alcohols under atmospheric-pressure H2 gas and ambient temperature conditions was developed by a water-soluble metal–ligand bifunctional catalyst [Cp*Ir(2,2′-bpyO)(OH)][Na] in water without addition of a base. The catalyst exhibited high activity for the hydrogenation of ketones and aldehydes. Furthermore, it was worth noting that many readily reducible or labile functional groups in the same molecule, such as cyan, nitro, and ester groups, remained unchanged. Interestingly, the unsaturated aldehydes can be also selectively hydrogenated to give corresponding unsaturated alcohols with remaining C=C bond in good yields. In addition, this reaction could be extended to gram levels and has a large potential of wide application in future industrial.
Method for synthesizing primary alcohol in water phase
-
Paragraph 0034-0035, (2021/07/14)
The invention discloses a method for synthesizing primary alcohol in a water phase. The method comprises the following steps: taking aldehyde as a raw material, selecting water as a solvent, and carrying out catalytic hydrogenation reaction on the aldehyde in the presence of a water-soluble catalyst to obtain the primary alcohol, wherein the catalyst is a metal iridium complex [Cp*Ir(2,2'-bpyO)(OH)][Na]. Water is used as the solvent, so that the use of an organic solvent is avoided, and the method is more environment-friendly; the reaction is carried out at relatively low temperature and normal pressure, and the reaction conditions are mild; alkali is not needed in the reaction, so that generation of byproducts is avoided; and the conversion rate of the raw materials is high, and the yield of the obtained product is high. The method not only has academic research value, but also has a certain industrialization prospect.
