2979-51-3Relevant articles and documents
Practical Chemoselective Acylation: Organocatalytic Chemodivergent Esterification and Amidation of Amino Alcohols with N-Carbonylimidazoles
Brown, Hailee,Heller, Stephen T.,Light, Christina,Medlin, Abigail,Nelson, Hope,Richard, William
supporting information, p. 22818 - 22825 (2021/09/13)
Chemoselective transformations are a cornerstone of efficient organic synthesis; however, achieving this goal for even simple transformations, such as acylation reactions, is often a challenge. We report that N-carbonylimidazoles enable catalytic chemodivergent aniline or alcohol acylation in the presence of pyridinium ions or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), respectively. Both acylation reactions display high and broad chemoselectivity for the target group. Unprecedented levels of chemoselectivity were observed in the DBU-catalyzed esterification: A single esterification product was obtained from a molecule containing primary aniline, alcohol, phenol, secondary amide, and N?H indole groups. These acylation reactions are highly practical as they involve only readily available, inexpensive, and relatively safe reagents; can be performed on a multigram scale; and can be used on carboxylic acids directly by in situ formation of the acylimidazole electrophile.
Development of New Benzylpiperazine Derivatives as σ1Receptor Ligands with in Vivo Antinociceptive and Anti-Allodynic Effects
Arena, Emanuela,Bonanno, Federica,Intagliata, Sebastiano,McLaughlin, Jay P.,Modica, Maria N.,Prezzavento, Orazio,Romeo, Giuseppe,Salerno, Loredana,Wilson, Lisa L.,Pittalà, Valeria
, p. 2003 - 2012 (2021/06/25)
σ-1 receptors (σ1R) modulate nociceptive signaling, driving the search for selective antagonists to take advantage of this promising target to treat pain. In this study, a new series of benzylpiperazinyl derivatives has been designed, synthesized, and characterized for their affinities toward σ1R and selectivity over the σ-2 receptor (σ2R). Notably, 3-cyclohexyl-1-{4-[(4-methoxyphenyl)methyl]piperazin-1-yl}propan-1-one (15) showed the highest σ1R receptor affinity (Ki σ1 = 1.6 nM) among the series with a significant improvement of the σ1R selectivity (Ki σ2/Ki σ1 = 886) compared to the lead compound 8 (Ki σ2/Ki σ1 = 432). Compound 15 was further tested in a mouse formalin assay of inflammatory pain and chronic nerve constriction injury (CCI) of neuropathic pain, where it produced dose-dependent (3-60 mg/kg, i.p.) antinociception and anti-allodynic effects. Moreover, compound 15 demonstrated no significant effects in a rotarod assay, suggesting that this σ1R antagonist did not produce sedation or impair locomotor responses. Overall, these results encourage the further development of our benzylpiperazine-based σ1R antagonists as potential therapeutics for chronic pain.
Carboxylic Acid Reductase Can Catalyze Ester Synthesis in Aqueous Environments
Pongpamorn, Pornkanok,Kiattisewee, Cholpisit,Kittipanukul, Narongyot,Jaroensuk, Juthamas,Trisrivirat, Duangthip,Maenpuen, Somchart,Chaiyen, Pimchai
supporting information, p. 5749 - 5753 (2021/02/01)
Most of the well-known enzymes catalyzing esterification require the minimization of water or activated substrates for activity. This work reports a new reaction catalyzed by carboxylic acid reductase (CAR), an enzyme known to transform a broad spectrum of carboxylic acids into aldehydes, with the use of ATP, Mg2+, and NADPH as co-substrates. When NADPH was replaced by a nucleophilic alcohol, CAR from Mycobacterium marinum can catalyze esterification under aqueous conditions at room temperature. Addition of imidazole, especially at pH 10.0, significantly enhanced ester production. In comparison to other esterification enzymes such as acyltransferase and lipase, CAR gave higher esterification yields in direct esterification under aqueous conditions. The scalability of CAR catalyzed esterification was demonstrated for the synthesis of cinoxate, an active ingredient in sunscreen. The CAR esterification offers a new method for green esterification under high water content conditions.
Silver-Catalyzed Acyl Nitrene Transfer Reactions Involving Dioxazolones: Direct Assembly of N-Acylureas
Yang, Zheng-Lin,Xu, Xin-Liang,Chen, Xue-Rong,Mao, Zhi-Feng,Zhou, Yi-Feng
supporting information, p. 648 - 652 (2020/12/21)
Dioxazolones and isocyanides are useful synthetic building blocks, and have attracted significant attention from researchers. However, the silver-catalyzed nitrene transfer reaction of dioxazolones has not been investigated to date. Herein, a silver-catalyzed acyl nitrene transfer reaction involving dioxazolones, isocyanides, and water was realized in the presence of Ag2O to afford a series of N-acylureas in moderate to good yields.
N-alkylimidazolium Salts Functionalized with p-Coumaric and Cinnamic Acid: A study of their antimicrobial and antibiofilm effects
Forero-Doria, Oscar,Araya-Maturana, Ramiro,Barrientos-Retamal, Anggela,Morales-Quintana, Luis,Guzmán, Luis
, (2019/10/02)
The bacterial resistance to antibiotics has compromised the therapies used for bacterial infections. Nowadays, many strategies are being carried out to address this problem. Among them, the use of natural compounds like cinnamic and p-coumaric acids stands out. Nevertheless, their utilization is limited because of their unfavorable physicochemical properties. Due to the lack of new therapeutic alternatives for bacterial infections, novel strategies have emerged, such as the use of ionic liquids; given that they can show a broad spectrum of antibacterial activity, this is why we herein report the antibacterial and antibiofilm activity of a series of N-alkylimidazolium salts functionalized with p-coumaric and cinnamic acids. The results from this study showed better antibacterial activity against Gram-positive bacteria, with a predominance of the salts derived from coumaric acid and a correlation with the chain length. Additionally, a lower efficacy was observed in the inhibition of biofilm formation, highlighting the antibiofilm activity against Staphylococcus aureus, which decreased the production of the biofilm by 52% over the control. In conclusion, we suggest that the salts derived from p-coumaric acid are good alternatives as antibacterial compounds. Meanwhile, the salt derived from cinnamic acid could be a good alternative as an antibiofilm compound.
HEAT BASE GENERATOR, CURABLE COMPOSITION, AND CURED ARTICLE
-
Paragraph 0046-0049; 0054-0055, (2020/01/07)
PROBLEM TO BE SOLVED: To provide a heat base generator high in light stability and stability around room temperature, and sufficiently functioning as a curing catalyst of a heat curable compound after heating, a curable composition containing the heat base generator and a cured article of the curable composition. SOLUTION: There is provided a cinnamic acid amide type heat base generator represented by the following general formula (1). In the general formula (1), R1 and R2 form a heterocycle having aromatic property together with a neighboring nitrogen atom, R3 and R4 are each independently a hydrogen atom, a halogen atom, or a monovalent organic group, R5 to R9 are each independently a group or an atom other than a hydrogen group and a group generating a phenolic hydroxyl group by heating. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors
Watanabe, Bunta,Kirikae, Hiroaki,Koeduka, Takao,Takeuchi, Yoshinori,Asai, Tomoki,Naito, Yoshiyuki,Tokuoka, Hideya,Horoiwa, Shinri,Nakagawa, Yoshiaki,Shimizu, Bun-ichi,Mizutani, Masaharu,Hiratake, Jun
, p. 2466 - 2474 (2018/04/30)
4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-coumaric, caffeic, and ferulic acids, and the regulatory position of 4CL in the phenylpropanoid pathway renders the enzyme an attractive target that controls the composition of phenylpropanoids in plants. In this study, we designed and synthesized mechanism-based inhibitors for 4CL in order to develop useful tools for the investigation of physiological functions of 4CL and chemical agents that modulate plant growth with the ultimate goal to produce plant biomass that exhibits features that are beneficial to humans. The acylsulfamide backbone of the inhibitors in this study was adopted as a mimic of the acyladenylate intermediates in the catalytic reaction of 4CL. These acylsulfamide inhibitors and the important synthetic intermediates were fully characterized using two-dimensional NMR spectroscopy. Five 4CL proteins with distinct substrate specificity from four plant species, i.e., Arabidopsis thaliana, Glycine max (soybean), Populus trichocarpa (poplar), and Petunia hybrida (petunia), were used to evaluate the inhibitory activity, and the half-maximum inhibitory concentration (IC50) of each acylsulfamide in the presence of 4-coumaric acid (100 μM) was determined as an index of inhibitory activity. The synthetic acylsulfamides used in this study inhibited the 4CLs with IC50 values ranging from 0.10 to 722 μM, and the IC50 values of the most potent inhibitors for each 4CL were 0.10–2.4 μM. The structure–activity relationship observed in this study revealed that both the presence and the structure of the acyl group of the synthetic inhibitors strongly affect the inhibitory activity, and indicates that 4CL recognizes the acylsulfamide inhibitors as acyladenylate mimics.
An Environmentally Sustainable Mechanochemical Route to Hydroxamic Acid Derivatives
Mocci, Rita,De Luca, Lidia,Delogu, Francesco,Porcheddu, Andrea
supporting information, p. 3135 - 3144 (2016/10/09)
An operationally simple, and cost efficient conversion of carboxylic acids into hydroxamic acid derivatives via a high-energy mechanochemical activation is presented. This ball milling methodology was applied to a wide variety of carboxylic acids dramatically improving purification issues associated with this class of molecules, which still remain one of the main bottlenecks of classical methodologies. (Figure presented.).
Hydroxamic acids block replication of hepatitis c virus
Ai, Teng,Xu, Yanli,Qiu, Li,Geraghty, Robert J.,Chen, Liqiang
, p. 785 - 800 (2015/01/30)
Intrigued by the role of protein acetylation in hepatitis C virus (HCV) replication, we tested known histone deacetylase (HDAC) inhibitors and a focused library of structurally simple hydroxamic acids for inhibition of a HCV subgenomic replicon. While known HDAC inhibitors with varied inhibitory profiles proved to be either relatively toxic or ineffective, structure-activity relationship (SAR) studies on cinnamic hydroxamic acid and benzo[b]thiophen-2-hydroxamic acid gave rise to compounds 22 and 53, which showed potent and selective anti-HCV activity and therefore are promising starting points for further structural optimization and mechanistic studies.
Ru-catalyzed highly chemo- and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters under neutral conditions
Ma, Xin,Li, Wanfang,Li, Xiaoming,Tao, Xiaoming,Fan, Weizheng,Xie, Xiaomin,Ayad, Tahar,Ratovelomanana-Vidal, Virginie,Zhang, Zhaoguo
supporting information; experimental part, p. 5352 - 5354 (2012/06/30)
Finely-tuned ruthenium-catalyzed highly chemoselective and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters at the carbonyl group was achieved under neutral reaction conditions (ee up to 97%). Both olefin and alkenyl halogen moieties, which are labile under hydrogenation conditions, remained untouched during the reaction.
