3467-59-2Relevant articles and documents
Synthesis of Arylamides via Ritter-Type Cleavage of Solid-Supported Aryltriazenes
Wippert, Nicolai A.,Jung, Nicole,Br?se, Stefan
supporting information, p. 568 - 572 (2019/09/03)
A novel route for the synthesis of N-arylamides via the cleavage of aryltriazenes with alkyl or aryl nitriles is presented. We developed a variation of the Ritter reaction that allows the use of acetonitrile as solvent and reagent in reactions with solid-supported precursors. The reaction was optimized for the generation of N-aryl acetamides using a diverse range of immobilized building blocks including o-, m-, and p-substituted aryltriazenes. The cleavage via the Ritter-type conversion was combined with an on-bead cross-coupling reaction of halogen-substituted aryltriazenes with pyrazoles. Additionally, the synthesis of on-bead generated arylboronic ester-substituted triazenes was shown. The developed procedure was further expanded to use other commercially available nitriles, such as acrylonitrile, benzonitrile, and chlorinated alkyl nitriles as suitable reagents for a Ritter-type cleavage of the prepared triazene linkers.
Method for preparing N-aryl amide without solvent and catalyst
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Paragraph 0013; 0014; 0021; 0022, (2017/08/29)
The invention discloses a method for preparing N-aryl amide without a solvent and a catalyst. The method is characterized by obtaining the N-aryl amide under solvent-free and catalyst-free action; a molar ratio of substituted meldrum acid and arylamine is (1 to 5) to (5 to 1). According to the method disclosed by the invention, the defects that acyl chloride, anhydride, a dehydration coupling reagent, the solvent, a phase transfer catalyst or a metal catalyst, and the like are required to be adopted in the prior art are overcome; the method has the following advantages that (1) the substituted meldrum acid is used as an acylating agent, so that pre-activation on carboxylic acid or use of the dehydration coupling reagent is avoided; (2) due to easiness in preparation of the substituted meldrum acid, certain difficult-to-obtain or expensive carboxylic acid and activated derivatives are prevented from being used; (3) a solvent-free mode is adopted, so that the use of a toxic organic solvent or emission of wastewater is avoided; (4) no acid, base or metal catalysts exist, the influence of the acid and the base on sensitive groups and equipment and the residue of metal ions in a product are avoided. A synthesis method disclosed by the invention can play an important role in industrial production for preparing the N-aryl amide and particularly for preparing the N-aryl amide with complex carboxylic acid.
Natural Abenquines and Their Synthetic Analogues Exert Algicidal Activity against Bloom-Forming Cyanobacteria
Nain-Perez, Amalyn,Barbosa, Luiz Cláudio Almeida,Maltha, Célia Regina álvares,Forlani, Giuseppe
, p. 813 - 818 (2017/05/05)
Abenquines are natural quinones, produced by some Streptomycetes, showing the ability to inhibit cyanobacterial growth in the 1 to 100 μM range. To further elucidate their biological significance, the synthesis of several analogues (4f-h, 5a-h) allowed us to identify some steric and electronic requirements for bioactivity. Replacing the acetyl by a benzoyl group in the quinone core and also changing the amino acid moiety with ethylpyrimidinyl or ethylpyrrolidinyl groups resulted in analogues 25-fold more potent than the natural abenquines. The two most effective analogues inhibited the proliferation of five cyanobacterial strains tested, with IC50 values ranging from 0.3 to 3 μM. These compounds may be useful leads for the development of an effective strategy for the control of cyanobacterial blooms.
Natural abenquines and synthetic analogues: Preliminary exploration of their cytotoxic activity
Nain-Perez, Amalyn,Barbosa, Luiz C.A.,Rodríguez-Hernández, Diego,Kramell, Annemarie E.,Heller, Lucie,Csuk, René
, p. 1141 - 1144 (2017/06/19)
In this study, we explore the cytotoxic activity of four natural abenquines (2a–d) and fourteen synthetic analogues (2e–j and 3a–h) against a panel of six human cancer cell lines using a SRB assay. It was found that most of the compounds revealed higher levels of cytotoxic activities than naturally occurring abenquines. The analogues carrying ethylpyrrolidinyl and ethylpyrimidinyl with either an acetyl group (2?h–i) or a benzoyl group (3f–g), were the most potent against all human cancer cell lines and displayed EC50 between a range of 0.6–3.4?μM. Notably, of the compounds tested, compound 2i proved the most cytotoxic against both ovarian (A2780) and breast (MCF7) cells, showing EC50?=?0.6 and 0.8?μM respectively. Likewise, the analogues 2i, 3f and 3?g showed strong activity against cell HT29 with EC50?=?0.9?μM for these compounds.
Tailoring Natural Abenquines to Inhibit the Photosynthetic Electron Transport through Interaction with the D1 Protein in Photosystem II
Nain-Perez, Amalyn,Barbosa, Luiz C.A.,Maltha, Celia R. A.,Giberti, Samuele,Forlani, Giuseppe
, p. 11304 - 11311 (2018/01/10)
Abenquines are natural N-acetylaminobenzoquinones bearing amino acid residues, which act as weak inhibitors of the photosynthetic electron transport chain. Aiming to exploit the abenquine scaffold as a model for the synthesis of new herbicides targeting photosynthesis, 14 new analogues were prepared by replacing the amino acid residue with benzylamines and the acetyl with different acyl groups. The synthesis was accomplished in three steps with a 68-95% overall yield from readily available 2,5-dimethoxyaniline, acyl chlorides, and benzyl amines. Key steps include (i) acylation of the aniline, (ii) oxidation, and (iii) oxidative addition of the benzylamino moiety. The compounds were assayed for their activity as Hill inhibitors, under basal, uncoupled, or phosphorylating conditions, or excluding photosystem I. Four analogues showed high effectiveness (IC50 = 0.1-0.4 μM), comparable with the commercial herbicide diuron (IC50 = 0.3 μM). The data suggest that this class of compounds interfere at the reducing side of photosystem II, having protein D1 as the most probable target. Molecular docking studies with the plastoquinone binding site of Spinacia oleracea further strengthened this proposal.
First total synthesis and phytotoxic activity of Streptomyces sp. metabolites abenquines
Nain-Perez, Amalyn,Barbosa, Luiz C.A.,Maltha, Celia R.A.,Forlani, Giuseppe
supporting information, p. 1811 - 1814 (2016/04/05)
The first total synthesis of abenquines A, B2, C and D has been achieved in three steps starting from commercially available 2,5-dimethoxyaniline, with overall yields of 41-61%. Four analogues bearing the amino acids d-valine (17), l-methionine (18), and glycine (19), and benzylamine (20), were also prepared in 45-72% yield. The inhibitory properties of these compounds were evaluated against the photoautotrophic growth of a model Synechococcus sp. strain. Abenquine C and its enantiomer were substantially ineffective, whereas all other abenquines significantly inhibited cell proliferation, with concentrations causing 50%-inhibition of algal growth ranging from 10-5 to 10-6 M.
Synthesis of new 3-(2-Chloroquinolin-3-yl)-5-phenylisoxazole derivatives via click chemistry approach
Ferna?ndez-Galleguillos, Carlos,Saavedra, Luis A.,Gutierrez, Margarita
, p. 365 - 371 (2014/02/14)
Herein, we report the synthesis of new substituted 3-(2-chloroquinolin-3- yl)-5-phenylisoxazole (3a-j) by click chemistry in good to moderate yields. This approach is based on the regioselective copper(I)-catalyzed cycloaddition between different nitrile oxides derived from 2-chloroquinoline- 3-carbaldehyde (2a-j) and phenylacetylene. Finally these derivatives were screened for their antibacterial evaluation in vitro against three Gram-negative clinical bacteria: Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii using standard methods.
Design of a hydrogen peroxide-activatable agent that specifically targets cancer cells
Vadukoot, Anish K.,Abdulsalam, Safnas F.,Wunderlich, Mark,Pullen, Eboni D.,Landero-Figueroa, Julio,Mulloy, James C.,Merino, Eddie J.
supporting information, p. 6885 - 6892 (2015/02/02)
Some cancers, like acute myeloid leukemia (AML), use reactive oxygen species to endogenously activate cell proliferation and angiogenic signaling cascades. Thus many cancers display increases in reactive oxygen like hydrogen peroxide concentrations. To translate this finding into a therapeutic strategy we designed new hydrogen peroxide-activated agents with two key molecular pharmacophores. The first pharmacophore is a peroxide-acceptor and the second is a pendant amine. The acceptor is an N-(2,5-dihydroxyphenyl)acetamide susceptible to hydrogen peroxide oxidation. We hypothesized that selectivity between AML and normal cells could be achieved by tuning the pendant amine. Synthesis and testing of fourteen compounds that differed at the pendent amine led to the identification of an agent (14) with 2 μM activity against AML cancer cells and an eleven fold-lower activity in healthy CD34+ blood stem cells. Interestingly, analysis shows that upon oxidation the pendant amine cyclizes, ejecting water, with the acceptor to give a bicyclic compound capable of reacting with nucleophiles. Preliminary mechanistic investigations show that AML cells made from addition of two oncogenes (NrasG12D and MLL-AF9) increase the ROS-status, is initially an anti-oxidant as hydrogen peroxide is consumed to activate the pro-drug, and cells respond by upregulating electrophilic defense as visualized by Western blotting of KEAP1. Thus, using this chemical approach we have obtained a simple, potent, and selective ROS-activated anti-AML agent.
Synthesis and biological evaluation of new rhodanine analogues bearing 2-chloroquinoline and benzo[h]quinoline scaffolds as anticancer agents
Ramesh, Vadla,Ananda Rao, Boddu,Sharma, Pankaj,Swarna,Thummuri, Dinesh,Srinivas, Kolupula,Naidu,Jayathirtha Rao, Vaidya
, p. 569 - 580 (2014/07/21)
Several rhodanine derivatives (9-39) were synthesized for evaluation of their potential as anticancer agents. Villsmeier cyclization to synthesize aza-aromatic aldehydes, rhodanine derivatives preparation and Knoevenagel type of condensation between the rhodanines and aza-aromatic aldehydes are key steps used for the synthesis of 31 compounds. In vitro antiproliferative activity of the synthesized rhodanine derivatives (9-39) was studied on a panel of six human tumor cell lines viz. HGC, MNK-74, MCF-7, MDAMB-231, DU-145 and PC-3 cell lines. Some of the compounds were capable of inhibiting the proliferation of cancer cell lines at a micromolar concentration. Six compounds are found to be potent against HGC cell lines; compound 15 is found to be active against HGC - Gastric, MCF7 - Breast Cancer and DU145 - Prostate Cancer cell lines; compound 39 is potent against MNK-74; four compounds are found to be potent against MCF-7 cell lines; three compounds are active against MDAMB-231; nine compounds are found to be potent against DU-145; three compounds are active against PC-3 cell lines. These compounds constitute a promising starting point for the development of novel and more potent anticancer agents in future.
Ph3P/I2-Catalyzed beckmann rearrangement of ketoximes into amides
Xu, Feng,Wang, Ni-Ge,Tian, You-Ping,Chen, Yong-Mei,Liu, Wei-Chun
experimental part, p. 3532 - 3539 (2012/10/08)
A Beckmann rearrangement of ketoximes reaction using triphenylphosphine/ iodine as an effective catalyst in acetonitrile at reflux temperature is reported. The results indicate that conversion of oximes to amides can be reached in good to excellent yields under optimal reaction conditions within several minutes. The reaction mechanism is also proposed. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
