- Characterization and Synthesis of Eudistidine C, a Bioactive Marine Alkaloid with an Intriguing Molecular Scaffold
-
An extract of Eudistoma sp. provided eudistidine C (1), a heterocyclic alkaloid with a novel molecular framework. Eudistidine C (1) is a racemic natural product composed of a tetracyclic core structure further elaborated with a p-methoxyphenyl group and a phenol-substituted aminoimidazole moiety. This compound presented significant structure elucidation challenges due to the large number of heteroatoms and fully substituted carbons. These issues were mitigated by application of a new NMR pulse sequence (LR-HSQMBC) optimized to detect four- and five-bond heteronuclear correlations and the use of computer-assisted structure elucidation software. Synthesis of eudistidine C (1) was accomplished in high yield by treating eudistidine A (2) with 4(2-amino-1H-imidazol-5-yl)phenol (4) in DMSO. Synthesis of eudistidine C (1) confirmed the proposed structure and provided material for further biological characterization. Treatment of 2 with various nitrogen heterocycles and electron-rich arenes provided a series of analogues (5-10) of eudistidine C. Chiral-phase HPLC resolution of epimeric eudistidine C provided (+)-(R)-eudistidine C (1a) and (-)-(S)-eudistidine C (1b). The absolute configuration of these enantiomers was assigned by ECD analysis. (-)-(S)-Eudistidine C (1b) modestly inhibited interaction between the protein binding domains of HIF-1α and p300. Compounds 1, 2, and 6-10 exhibited significant antimalarial activity against Plasmodium falciparum.
- Chan, Susanna T.S.,Nani, Roger R.,Schauer, Evan A.,Martin, Gary E.,Williamson, R. Thomas,Saurí, Josep,Buevich, Alexei V.,Schafer, Wes A.,Joyce, Leo A.,Goey, Andrew K. L.,Figg, William D.,Ransom, Tanya T.,Henrich, Curtis J.,McKee, Tawnya C.,Moser, Arvin,MacDonald, Scott A.,Khan, Shabana,McMahon, James B.,Schnermann, Martin J.,Gustafson, Kirk R.
-
-
Read Online
- Design and synthesis of coumarin-glyoxal hybrids for spermicidal and antimicrobial actions: A dual approach to contraception
-
Today there is an urgent need for safe and effective dual-purpose contraceptive agents, which can simultaneously prevent unintended pregnancies and sexually transmitted infections (STI). There are several naturally occurring antimicrobial and antibiotic drugs (novobiocin, coumermycin and chlorobiocin) reported in the literature, which are based on 4-hydroxy coumarins as the active pharmacophore. Based on these interesting reports, we designed and synthesized a library of new 4-hydroxy coumarin derivatives and evaluated them for spermicidal activity. Among the tested compounds, two compounds (2a and 2d) displayed better activity (greater than 95% sperm immobilization at 0.5 mM concentration) than the positive control nonoxynol-9 (N-9). Furthermore, all the compounds were screened for antimicrobial activity against different strains of Trichomonas vaginalis and two compounds (2c and 2h) exhibited potent activity as compared to the reference drug metronidazole. The cytotoxicity assay showed that most of these compounds were safer than the N-9 against the human cervical HeLa cell line and normal vaginal flora Lactobacillus jensenii strains. The studies have demonstrated that compound (2a) is a potential lead to develop a dually active vaginal contraceptive.
- Gupta, Swati,Kushwaha, Bhavana,Srivastava, Akansha,Maikhuri, Jagdamba Prasad,Sankhwar, Satya N.,Gupta, Gopal,Dwivedi, Anil Kumar
-
-
Read Online
- Structural elucidation and synthesis of eudistidine A: An unusual polycyclic marine alkaloid that blocks interaction of the protein binding domains of p300 and HIF-1α
-
Low oxygen environments are a hallmark of solid tumors, and transcription of many hypoxia-responsive genes needed for survival under these conditions is regulated by the transcription factor HIF-1 (hypoxia-inducible factor 1). Activation of HIF-1 requires binding of its α-subunit (HIF-1α) to the transcriptional coactivator protein p300. Inhibition of the p300/HIF-1α interaction can suppress HIF-1 activity. A screen for inhibitors of the protein binding domains of p300 (CH1) and HIF-1α (C-TAD) identified an extract of the marine ascidian Eudistoma sp. as active. Novel heterocyclic alkaloids eudistidines A (1) and B (2) were isolated from the extract, and their structures assigned by spectroscopic analyses. They contain an unprecedented tetracyclic core composed of two pyrimidine rings fused with an imidazole ring. Eudistidine A (1) was synthesized in a concise four-step sequence featuring a condensation/cyclization reaction cascade between 4-(2-aminophenyl)pyrimidin-2-amine (3) and 4-methoxy-phenylglyoxal (4), while eudistidine B (2) was synthesized in a similar fashion with glyoxylic acid (5) in place of 4. Naturally occurring eudistidine A (1) effectively inhibited CH1/C-TAD binding with an IC50 of 75 μM, and synthetic 1 had similar activity. The eudistidine A (1) scaffold, which can be synthesized in a concise, scalable manner, may provide potential therapeutic lead compounds or molecular probes to study p300/HIF-1α interactions and the role these proteins play in tumor response to low oxygen conditions. The unique structural scaffolds and functional group arrays often found in natural products make these secondary metabolites a rich source of new compounds that can disrupt critical protein-protein binding events.
- Chan, Susanna T. S.,Patel, Paresma R.,Ransom, Tanya R.,Henrich, Curtis J.,Mckee, Tawnya C.,Goey, Andrew K. L.,Cook, Kristina M.,Figg, William D.,Mcmahon, James B.,Schnermann, Martin J.,Gustafson, Kirk R.
-
-
Read Online
- Synthesis of α-keto aldehydes via selective Cu(i)-catalyzed oxidation of α-hydroxy ketones
-
An efficient approach to synthesize α-keto aldehydes was established through selective oxidation of α-hydroxy ketones catalyzed by Cu(i) using oxygen as oxidant. A wide array of α-keto aldehydes was prepared with isolated yields of up to 87%. The potential utilization of this reaction was evaluated by gram-scale reactions and synthetic applications.
- Zheng, Shasha,Smit, Wietse,Spannenberg, Anke,Tin, Sergey,de Vries, Johannes G.
-
supporting information
p. 4639 - 4642
(2022/04/19)
-
- Gold-catalyzed oxidation of terminal alkynes to glyoxals and their reactions with 2-phenylimidazo[1,2-a]pyridines: one-pot synthesis of 1,2-diones
-
A novel one-pot protocol for the convenient and efficient synthesis of (2-phenylimidazo[1,2-a]pyridin-3-yl)alkane-1,2-diones (3) in good yields (32-88%) from 2-phenylimidazo[1,2-a]pyridines (1) and terminal alkynes (2) has been established with a wide range of substrate scope. A tandem reaction sequence containing gold-catalyzed double oxidations of terminal alkynes to generate glyoxals, nucleophilic addition of 2-phenylimidazo[1,2-a]pyridines to glyoxals to yield α-hydroxyl ketones, and oxygenation of the α-hydroxyl ketones to afford the final products3under air atmosphere is involved in this method. Simple operation, mild reaction conditions, and widely available substrates make this strategy more affordable.
- Liao, Shengrong,Lin, Xiuping,Liu, Yonghong,Wang, Junfeng,Xu, Huayan,Yang, Bin,Zhou, Xuefeng
-
p. 8735 - 8739
(2021/10/22)
-
- A novel class for carbonic anhydrases inhibitors and evaluation of their non-zinc binding
-
In this study, 23 different imidazole derivatives were synthesized, and the inhibitory properties of these derivatives against carbonic anhydrase I and II isoenzymes were investigated for the first time. The inhibition concentrations of the imidazole derivatives were found to be in the range of 2.89–115.5 nM. Docking studies examined the binding properties of the imidazole derivatives, and the structure–activity relationship is discussed. Theoretical calculations showed that the binding mode of the imidazole ring was non-zinc binding.
- Kuzu, Burak,Tan, Meltem,Gül?in, ?lhami,Menges, Nurettin
-
-
- Ynonylation of Acyl Radicals by Electroinduced Homolysis of 4-Acyl-1,4-dihydropyridines
-
Herein we report the conversion of 4-Acyl-1,4-dihydropyridines (DHPs) into ynones under electrochemical conditions. The reaction proceeds via the homolysis of acyl-DHP under electron activation. The resulting acyl radicals react with hypervalent iodine(III) reagents to form the target ynones or ynamides in acceptable yields. This mild reaction condition allows wider functionality tolerance that includes halides, carboxylates, or alkenes. The synthetic utility of this methodology is further demonstrated by the late-stage modification of complex molecules.
- Luo, Xiaosheng,Wang, Ping
-
supporting information
p. 4960 - 4965
(2021/07/20)
-
- Catalytic Asymmetric Darzens-Type Epoxidation of Diazoesters: Highly Enantioselective Synthesis of Trisubstituted Epoxides
-
Highly enantioselective Darzens-type epoxidation of diazoesters with glyoxal derivatives was accomplished using a chiral boron–Lewis acid catalyst, which facilitated asymmetric synthesis of trisubstituted α,β-epoxy esters. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction proceeded in high yield (up to 99 %) with excellent enantio- and diastereoselectivity (up to >99 % ee and >20:1 dr, respectively). The synthetic potential of this method was illustrated by conversion of the products to various compounds such as epoxy γ-butyrolactone, tertiary β-hydroxy ketone and epoxy diester.
- Jeong, Hye-Min,Nam, Dong Guk,Ryu, Do Hyun,Shim, Su Yong
-
supporting information
p. 22236 - 22240
(2021/09/13)
-
- One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors
-
A green and efficient one-pot multi-component protocol was developed for the synthesis of some novel dihydrochromeno[4,3-b]pyrrol-3-yl derivatives through the reaction of arylglyoxals, malono derivatives, and different 4-amino coumarins in ethanol at reflux condition. In this method, all products were obtained in good to excellent yield. Next, all synthesized derivatives were evaluated for their α-glucosidase inhibitory activity. Most of the compounds displayed potent inhibitory activities with IC50 values in the range of 48.65 ± 0.01–733.83 ± 0.10?μM compared to the standard inhibitor acarbose (IC50 = 750.90 ± 0.14?μM). The kinetic study of compound 5e as the most potent derivative (IC50 = 48.65 ± 0.01?μM) showed a competitive mechanism with a Ki value of 42.6?μM. Moreover, docking studies revealed that dihydrochromeno[4,3-b]pyrrol-3-yl effectively interacted with important residues in the active site of α-glucosidase.
- Faramarzi, Mohammad Ali,Hasaninejad, Alireza,Iraji, Aida,Karami, Malihe,Mahdavi, Hossein,Mahdavi, Mohammad,Mojtabavi, Somayeh
-
-
- Synthesis and solid-state luminescence of highly-substituted 6-amino-2H-pyran-2-one derivatives
-
A fast and convenient synthesis and solid-state luminescence properties of new highly-substituted 6-amino-2H-pyran-2-one derivatives is described. These compounds were obtained from inexpensive and available 2-acyl(aroyl)-1,3-dicyano-1,3-bis-methoxycarbonylpropenides via regioselective heterocyclization under the action of sulfuric and hydroiodic acid. Compounds containing 6-amino-2H-pyran-2-one moiety are nearly unstudied, but are of interest for obtaining condensed biologically active compounds based on this scaffold.
- Karpov, Sergey,Kayukov, Yakov,Grigor'ev, Arthur,Nasakin, Oleg,Kayukova, Olga,Tafeenko, Viktor
-
-
- Antiproliferative Activity of 2-Aroyland 2-Heteroyl-1,1,3,3-Tetracyanoprop-2-en-1-ides
-
The influence of previously synthesized 2-aroyl-1,1,3,3-tetracyanoprop-2-en-1-ides on the growth of conditionally normal and tumor cells was studied in continuation of a search for new anticancer drugs. Cytotoxicities of the compounds were studied with respect to human tumor cell lines from the ATCC. All compounds were ineffective against melanoma and lung and ovary cancer cell lines and exhibited moderate activity in the other cases. The tested compounds exhibited highly selective effects because they were safe for conditionally normal skin fibroblasts.
- Kayukov, Ya. S.,Mar’yasov, M. A.,Nasakin, O. E.
-
-
- Pyrimidine-containing tri-substituted imidazole compound and application thereof
-
The invention relates to a pyrimidine-containing tri-substituted imidazole compound and application thereof. The compound has a structure shown as a formula (I). The compound can be used for effectively inhibiting EGFR (epidermal growth factor receptor) C797S mutation including EGFR ex19del/T790M/C797S and L858R/T790M/C797S; meanwhile, the compounds also have high inhibitory activity on single-point mutation L858R, ex19del and double-point mutation such as L858R/T790M, ex19del/T790M and the like, and moreover, the compounds have a weak inhibitory effect on wild EGFR (epidermal growth factor receptor), namely, the compounds have very good selectivity. The compound has potential to become a drug for treating malignant tumors carrying EGFR C797S mutation, especially non-small cell lung cancer(NSCLC), and has great application value.
- -
-
Paragraph 0375; 0376
(2020/07/15)
-
- Asymmetric Conjugate Addition of α-Cyanoketones to Benzoyl Acrylonitrile Derivatives Using a Diaminomethylenemalononitrile Organocatalyst
-
A diaminomethylenemalononitrile (DMM) organocatalyst was used to efficiently promote asymmetric conjugate addition of various α-cyanoketones to benzoyl acrylonitrile derivatives. The corresponding 1,5-dicarbonyl compounds containing vicinal tertiary and quaternary stereogenic centers are versatile synthetic intermediates and were obtained in good yields and with excellent enantioselectivities (up to 96% ee). The present study describes the first successful examples of asymmetric conjugate addition reactions of α-cyanoketones with benzoyl acrylonitriles. In addition, the DMM organocatalyst can be recovered and reused up to five times without significant loss of either catalytic activity or enantioselectivity.
- Akutsu, Hiroshi,Nakashima, Kosuke,Kanetsuna, Yuta,Kawada, Masahiro,Hirashima, Shin-Ichi,Miura, Tsuyoshi
-
p. 3874 - 3880
(2020/10/06)
-
- Nature of the Nucleophilic Oxygenation Reagent Is Key to Acid-Free Gold-Catalyzed Conversion of Terminal and Internal Alkynes to 1,2-Dicarbonyls
-
2,3-Dichloropyridine N-oxide, a novel oxygen transfer reagent, allows the conductance of the gold(I)-catalyzed oxidation of alkynes to 1,2-dicarbonyls in the absence of any acid additives and under mild conditions to furnish the target species, including those derivatized by highly acid-sensitive groups. The developed strategy is effective for a wide range of alkyne substrates such as terminal- and internal alkynes, ynamides, alkynyl ethers/thioethers, and even unsubstituted acetylene (40 examples; yields up to 99%). The oxidation was successfully integrated into the trapping of reactive dicarbonyls by one-pot heterocyclization and into the synthesis of six-membered azaheterocycles. This synthetic acid-free route was also successfully applied for the total synthesis of a natural 1,2-diketone.
- Dubovtsev, Alexey Yu.,Shcherbakov, Nikolay V.,Dar'in, Dmitry V.,Kukushkin, Vadim Yu.
-
p. 745 - 757
(2020/02/04)
-
- Mono- or di-substituted imidazole derivatives for inhibition of acetylcholine and butyrylcholine esterases
-
Mono- or di-substituted imidazole derivatives were synthesized using a one-pot, two-step strategy. All imidazole derivatives were tested for AChE and BChE inhibition and showed nanomolar activity similar to that of the test compound donepezil and higher than that of tacrine. Structure activity relationship studies, docking studies to on X-ray crystal structure of AChE with PDB code 1B41, and adsorption, distribution, metabolism, and excretion (ADME) predictions were performed. The synthesized core skeleton was bound to important regions of the active site of AChE such as the peripheral anionic site (PAS), oxyanion hole (OH), and anionic subsite (AS). Selectivity of the reported test compounds was calculated and enzyme kinetic studies revealed that they behave as competitive inhibitors, while two of the test compounds showed noncompetitive inhibitory behavior. ADME predictions revealed that the synthesized molecules might pass through the blood brain barrier and intestinal epithelial barrier and circulate freely in the blood stream without binding to human serum albumin. While the toxicity of one compound on the WS1 (skin fibroblast) cell line was 1790 μM, its toxicity on the SH-SY5Y (neuroblastoma) cell line was 950 μM.
- Kuzu, Burak,Tan, Meltem,Taslimi, Parham,Gül?in, ?lhami,Ta?p?nar, Mehmet,Menges, Nurettin
-
p. 187 - 196
(2019/02/06)
-
- A simple route for synthesis of 5-(furan-3-yl)barbiturate/thiobarbiturate derivatives via a multi-component reaction between arylglyoxals, acetylacetone and barbituric/thiobarbituric acid
-
An effective protocol for the synthesis of 5-(furan-3-yl)barbiturate and 5-(furan-3-yl)thiobarbiturate derivatives through a one-pot three-component reaction of readily available starting materials arylglyoxals, barbituric acid or thiobarbituric acid and acetylacetone in water as solvent is reported.
- Dehghanzadeh, Fatemeh,Shahrokhabadi, Fereshteh,Anary-Abbasinejad, Mohammad
-
p. 133 - 141
(2019/04/17)
-
- Modular Synthesis of Di- A nd Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors
-
A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted NH-imidazoles (23%-85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation-condensation protocol, followed by bromination and Suzuki coupling in the imidazole ring to yield trisubstituted NH-imidazoles (23%-69%, three steps). This approach was also employed in the synthesis of known inhibitor GSK3037619A.
- De Toledo, Ian,Grigolo, Thiago A.,Bennett, James M.,Elkins, Jonathan M.,Pilli, Ronaldo A.
-
p. 14187 - 14201
(2019/10/16)
-
- Reactions of cyclohexyl isocyanide, dialkyl acetylenedicarboxylates and 1-aryl-2-ene-3-acetyl-1,4-diketones: One-pot synthesis of highly functionalized 5-cyclohexylimino-2,5-dihydrofurans
-
Dihydrofurans are important intermediates in organic synthesis, and are also important starting materials used in syntheses of a number of natural products. A facile synthesis of highly functionalized 5- cyclohexylimino-2,5-dihydrofuran derivatives by the multi-component reaction of cyclohexyl isocyanide, dialkyl acetylenedicarboxylates and 1-aryl-2-ene-3-acetyl-1,4-diketones is described.
- Latifi, Mahsa,Talebdizaeh, Mahdiyeh,Anary-Abbasinejad, Mohammad
-
-
- Synthesis of fused pyrroles containing 4-hydroxycoumarins by regioselective metal-free multicomponent reactions
-
The reaction of arylglyoxals, 4-hydroxycoumarin, and aromatic amines such as 7-amino-2-methylchromone, 6/7-aminoflavone, 7-amino-4-methylcoumarin, 1-amino-9-fluorenone, 1-aminoanthraquinone and aniline derivatives in acetic acid medium under microwave conditions provides the corresponding regioselective fused pyrroles having hydroxycoumarin and aryl substituents. Alternatively, we have developed another method using in situ arylglyoxals from acetophenone derivatives by I2/DMSO promoted C-H oxidation followed by one-pot three component cyclization reactions to provide similar fused pyrroles. Using both the methods a series of novel pyrroles fused with pharmacologically important chromone, flavone, coumarin, fluorenone, and anthraquinone moieties were synthesized under metal-free reaction conditions in good to very good yields within a short reaction time. The structures of the synthesized fused pyrroles have been unambiguously confirmed by spectroscopic techniques, mass analysis and single crystal XRD.
- Mishra, Richa,Jana, Asim,Panday, Anoop Kumar,Choudhury, Lokman H.
-
p. 3289 - 3302
(2018/05/22)
-
- Oxidative C-C Bond Cleavage for the Synthesis of Aryl Carboxylic Acids from Aryl Alkyl Ketones
-
A metal-free and one-pot two-step synthesis of aryl carboxylic acids from aryl alkyl ketones has been achieved. The reactions were performed with iodine as the catalyst, DMSO and TBHP as the oxidants. Under the optimal reaction conditions, a number of aryl alkyl ketones could be converted into their corresponding aryl carboxylic acids in good to excellent yields (up to 94%).
- Xu, Liang,Wang, Shengpeng,Chen, Bajin,Li, Meichao,Hu, Xinquan,Hu, Baoxiang,Jin, Liqun,Sun, Nan,Shen, Zhenlu
-
supporting information
p. 1505 - 1509
(2018/05/25)
-
- Synthesis of novel imidazopyridines and their biological evaluation as potent anticancer agents: A promising candidate for glioblastoma
-
Novel imidazopyridine derivatives were synthesized according to a very simple protocol and then subjected to cytotoxicity testing against LN-405 cells. Two of the compounds exhibited antiproliferative effects on LN-405 cells at 10 and 75 μM and were selected as lead compounds for further study. Safety experiment for lead compounds on WS1 was carried out and IC50 values were calculated as 480 and 844 μM. LN-405 cell line were incubated with the lead compounds and then tested for DNA damage by comet assay and effects on cell cycle using flow cytometry. The results of these two tests showed that both lead compounds affected the G0/G1 phase and did not allow the cells to reach the synthesis phase. The log BB (blood–brain barrier) and Caco-2 permeability of the synthesized molecules were calculated and it was shown that imidazopyridine derivatives taken orally are likely to pass through gastrointestinal membrane and the blood–brain barrier.
- Gü?lü, Dilek,Kuzu, Burak,Tozlu, ?srafil,Ta?p?nar, Filiz,Canp?nar, Hande,Ta?p?nar, Mehmet,Menges, Nurettin
-
supporting information
p. 2647 - 2651
(2018/07/06)
-
- Enantioselective Cyanosilylation of α,α-Dialkoxy Ketones by Using Phosphine-Thiourea Dual-Reagent Catalysis
-
The first highly enantioselective cyanosilylation of α,α-dialkoxy ketones enabled by a dual-reagent catalysis has been developed. With the combination of a chiral bifunctional phosphine-thiourea and methyl acrylate, the key organophosphorus zwitterion intermediate was generated in situ as a novel Lewis base, which catalyzed the enantioselective cyanosilylation reaction in excellent yields (up to 99 %) with good-to-excellent enantioselectivities (up to 94 % ee).
- Yu, Qi-Wen,Wu, Lu-Ping,Kang, Tian-Chen,Xie, Jin,Sha, Feng,Wu, Xin-Yan
-
supporting information
p. 3992 - 3996
(2018/07/31)
-
- Iodine-Promoted One-pot Synthesis of Highly Substituted 4-Aminopyrroles and Bis-4-aminopyrrole from Aryl Methyl Ketones, Arylamines, and Enamines
-
An iodine-promoted one-pot synthesis of functionally diverse and highly substituted 4-aminopyrroles directly from aryl methyl ketones, arylamines, and enamines was developed. The reaction involves in-situ oxidation of aryl methyl ketone to glyoxal, subsequent imine formation by aniline, followed by nucleophilic addition of enamine, and cyclization to afford highly substituted 4-aminopyrroles. This reaction involved the formation of two C?N bonds and one C?C bond by a formal [1+1+3] annulation approach. The present method provides an interesting framework of two 4-aminopyrrole units directly attached to a biphenyl core by the reaction of 4,4′-diacyl biphenyl, amine, and enamine groups. This Hantzsch-type one-pot reaction provides diverse 4-aminopyrroles, which could be useful in medicinal/material chemistry. (Figure presented.).
- Jalani, Hitesh B.,Mali, Jyotirling R.,Park, Hyejun,Lee, Jae Kyun,Lee, Kiho,Lee, Kyeong,Choi, Yongseok
-
supporting information
p. 4073 - 4079
(2018/09/25)
-
- Direct preparation of indole hemiaminals through organocatalytic nucleophilic addition of indole to aldehydes
-
Hemiaminals are common in natural products as well as bioactive compounds. Hemiaminals with an indole moiety are particularly attractive due to the significant bioactivity of indoles. Herein, we reported an efficient organocatalyzed indole N-1 nucleophilic addition of α-oxoaldehydes to deliver various indole hemiaminals in good yields (up to 92percent) and excellent regioselectivities with DABCO or triethylamine as the catalyst. The method is characterized by mild reaction conditions, widely available reagents, and general substrate scope, and it is also applicable to late-stage transformations without affecting the hemiaminal group. In addition, we carried out this reaction in an enantioselective fashion in good yields and high ee values with two general substrates.
- Chen, Zhili,Li, Yige,Qin, Wenling,Zhang, Nan
-
supporting information
p. 4063 - 4070
(2018/10/15)
-
- Visible-light assisted one-pot preparation of aryl glyoxals from acetoarylones via in-situ arylacyl bromides formation: Selenium-free approach to acetoarylones oxidation
-
A novel visible-light (blue LEDs: hν?=?425?±?15?nm) photocatalyzed one-pot method for the synthesis of electronically diverse aryl glyoxals in good to excellent yields from acetoarylones and green regents such as air, vitamin C and dioxane dibromide has been described. In addition, an application of the current methodology has been demonstrated for the oxidation of monoamine oxidase-B inhibitors, i.e., 1-(4-((4-fluorobenzyl)oxy)phenyl)ethanone and 1-(3-((4-chlorobenzyl)oxy)phenyl)ethanone. This finding may serves as a valuable alternative to the traditional acetoarylones oxidation reactions conducted using selenium dioxide a harmful and unselective reagent known to simultaneously oxidize allylic, benzylic, [sbnd]CH3and so on.
- Natarajan, Palani,Manjeet,Kumar, Naveen,Devi, Sapna,Mer, Kalyani
-
supporting information
p. 658 - 662
(2017/01/25)
-
- Design, synthesis, and biological evaluation of hydantoin bridged analogues of combretastatin A-4 as potential anticancer agents
-
A series of novel hydantoin-bridged analogues of combretastatin A-4 (CA-4) were designed, synthesized and evaluated for antiproliferative activities in vitro and in vivo. The most potent compound 8d, showed potent cytotoxicity against four human cancer cell lines with IC50 values of 0.186–0.279 μM, and possessed the efficacy of inhibiting tubulin polymerization, disrupting in vitro vascularization, blocking cell cycle in G2/M phase and inducing cell apoptosis. In the nude mice xenograft model, 8d significantly inhibited the tumor growth and showed low toxicity. Further chiral separation proved (R)-(?)-8d to be the preferential enantiomer with IC50 values of 0.081–0.157 M. These results indicated that the hydantoin derivatives merit further investigation as potential anticancer agents that inhibit tubulin polymerization.
- Zhang, Mao,Liang, Yu-Ru,Li, Huan,Liu, Ming-Ming,Wang, Yang
-
p. 6623 - 6634
(2017/11/13)
-
- Novel and convenient one-pot strategy for regioselective synthesis of new 5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives
-
Abstract: We describe a novel and simple regioselective synthesis of 5-aryl-3-methyl-1-phenyl-1,2-dihydro-7aH-pyrazolo[3,4-c]pyridazin-7a-ol derivatives via one-pot three-component reaction of arylglyoxalmonohydrates, 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and hydrazine hydrate in presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) as base-organocatalyst at room temperature in acetonitrile. This one-pot method has the advantages of simple methodology, high atom economy, cost-effectiveness, high regioselectivity, and easy workup. Graphical Abstract: [Figure not available: see fulltext.].
- Rimaz, Mehdi,Mousavi, Hossein,Nikpey, Laya,Khalili, Behzad
-
p. 3925 - 3937
(2017/06/20)
-
- Synthesis of Some 5-[2-Aryl-2-oxoethyl]-1,3-dimethylpyrimidine-2,4,6-trione Derivatives by a One-pot, Three-component Reaction
-
This study reports the reduction of á,a-unsaturated ketones 4a-g, formed by condensation of arylglyoxals 2a-g with 1,3-dimethylbarbituric acid (3) by L-cysteine (5) in the presence of phosphotungstic acid as a catalyst. This reaction leads to the formation of 5-[2-aryl-2-oxoethyl]-1,3-dimethylpyrimidine-2,4,6-triones 6a-g, with no sign of any heterocyclic product formation. The structure of compound 6f was confirmed by X-ray crystallography.
- Khalafy, Jabbar,Ezzati, Mahnaz,Madadi, Parinaz,Marjani, Ahmad Poursattar,Asl, Hooman Yaghoobnejad
-
p. 132 - 136
(2017/11/06)
-
- Synthesis of 2-acyl-benzo[1,3-d]selenazoles via domino oxidative cyclization of methyl ketones with bis(2-aminophenyl) diselenide
-
A general, practical and simple one-pot synthesis of 2-acyl-benzo[1,3-d]selenazoles was developed by reacting a wide range of 2-arylethane-1,2-diones, generated in situ from commercially available aryl methyl ketones, with bis(2-aminophenyl) diselenide, promoted by Na2S2O5 in DMSO at 100 °C. Comparatively, the reactions were conducted under conventional heating and microwave irradiation. The use of focused microwave irradiation drastically decreased the reaction time from 48 to 2 h with a gain in the reaction yield for most cases. Still, 2-phenylacyl-benzo[1,3-d]selenazole was elected to react with sodium borohydride and butylmagnesium bromide, giving the respective secondary and tertiary alcohols under mild reaction conditions.
- Balaguez, Renata A.,Betin, Eduardo S.,Barcellos, Thiago,Lenard?o, Eder J.,Alves, Diego,Schumacher, Ricardo F.
-
supporting information
p. 1483 - 1487
(2017/02/23)
-
- Iridium-Catalyzed Asymmetric Hydrogenation of Unsaturated Piperazin-2-ones
-
Two different iridium catalyst systems, generated from the ruthenocene-based phosphine-oxazoline ligand tBu-mono-RuPHOX or the diphosphine ligand BINAP, were developed for the asymmetric hydrogenation of 5,6-dihydropyrazin-2(1H)-ones, affording chiral piperazin-2-ones in good yields and with moderate to good ees. Different catalytic behaviors for the hydrogenation of these types of substrate were observed with these two catalyst systems. Our tBu-mono-RuPHOX ligand, which bears a ruthenocene scaffold with planar chirality, was found to be the best ligand for the [Ir(L)(COD)]BArF catalyst system, affording the desired products with up to 94% ee. (Figure presented.).
- Wang, Yanzhao,Liu, Yuanyuan,Li, Kun,Yang, Guoqiang,Zhang, Wanbin
-
supporting information
p. 1933 - 1941
(2017/06/09)
-
- Palladium-catalyzed decarboxylative, decarbonylative and dehydrogenative C(sp2)-H acylation at room temperature
-
Over the past few decades, an impressive array of C-H activation methodology has been developed for organic synthesis. However, due to the inherent inertness of the C-H bonds (e.g. ~110 kcal mol-1 for the cleavage of C(aryl)-H bonds) harsh reaction conditions have been realized to overcome high energetic transition states resulting in a limited substrate scope and functional group tolerance. Therefore, the development of mild C-H functionalization protocols is in high demand to exploit the full potential of the C-H activation strategy in the synthesis of a complex molecular framework. Although, electron-rich substrates undergo electrophilic metalation under relatively mild conditions, electron-deficient substrates proceed through a rate-limiting C-H insertion under forcing conditions at high temperature. In addition, a stoichiometric amount of toxic silver salt is frequently used in palladium catalysis to facilitate the C-H activation process which is not acceptable from the environmental and industrial standpoint. We report herein, a Pd(ii)-catalyzed decarboxylative C-H acylation of 2-arylpyridines with α-ketocarboxylic acids under mild conditions. The present protocol does not require stoichiometric silver(i) salts as additives and proceeds smoothly at ambient temperature. A novel decarbonylative C-H acylation reaction has also been accomplished using aryl glyoxals as acyl surrogates. Finally, a practical C-H acylation via a dehydrogenative pathway has been demonstrated using commercially available benzaldehydes and aqueous hydroperoxides. We also disclose that acetonitrile solvent is optimal for the acylation reaction at room temperature and has a prominent role in the reaction outcome. Control experiments suggest that the acylation reaction via decarboxylative, decarbonylative and dehydrogenative proceeds through a radical pathway. Thus we disclose a practical protocol for the sp2 C-H acylation reaction.
- Hossian, Asik,Manna, Manash Kumar,Manna, Kartic,Jana, Ranjan
-
supporting information
p. 6592 - 6603
(2017/08/16)
-
- Experimental and Theoretical Studies on Iron-Promoted Oxidative Annulation of Arylglyoxal with Alkyne: Unusual Addition and Migration on the Aryl Ring
-
An Fe(III)-promoted oxidative annulation reaction was developed for the synthesis of 1,2-naphthoquinones. A variety of substituted arylglyoxals and internal alkynes undergo the transformation in the presence of FeCl3 at room temperature to afford the 1,2-naphthoquinone products in good yields in a short reaction time. Interestingly, the products show unusual pseudomigration of the substituent on the arene ring of arylglyoxals. A possible mechanism involving Fe(III)-promoted formation of a vinyl cation from arylglyoxal and alkyne, electrophilic addition of the vinyl cation to the ipso carbon of the aryl group to give a spiral intermediate, and then migration of the keto carbon to the ortho carbon was proposed as key steps and verified using quantum mechanics.
- Hung, Chen-Hsun,Gandeepan, Parthasarathy,Cheng, Lin-Chieh,Chen, Liang-Yu,Cheng, Mu-Jeng,Cheng, Chien-Hong
-
supporting information
p. 17015 - 17021
(2017/12/06)
-
- HYPOXIA-INDUCIBLE FACTOR 1 (HIF-1) INHIBITORS
-
Embodiments of small molecule inhibitors of hypoxia inducible factor 1 (HIF-1) and pharmaceutical compositions thereof are disclosed. The disclosed compounds suppress HIF-1 activity by inhibiting the interaction between the HIF- 1 α subunit and transcriptional co-activator protein p300. Embodiments of methods for making and using the small molecule inhibitors are also disclosed.
- -
-
Page/Page column 43
(2016/12/12)
-
- Rh-catalyzed asymmetric hydrogenation of racemic aldimines via dynamic kinetic resolution
-
Catalyzed by a rhodium complex of P-stereogenic diphosphine ligand trichickenfootphos (TCFP), asymmetric hydrogenation of racemic aldimines via dynamic kinetic resolution has been realized for the preparation of chiral arylglycines with good yields and enantioselectivities.
- Fan, Dongyang,Lu, Jian,Liu, Yang,Zhang, Zhenfeng,Liu, Yangang,Zhang, Wanbin
-
p. 5541 - 5547
(2016/08/05)
-
- Synthesis and X-ray Characterization of Alkali Metal 2-Acyl-1,1,3,3-tetracyanopropenides
-
A novel route for synthesis of 2-acyl-1,1,3,3-tetracyanopropenides (ATCN) salts in high yields and excellent purities starting from readily available methyl ketones, malononitrile, bromine, and alkali metal acetates is reported. The starting aryl(heteroaryl) methyl ketones were oxidized to the corresponding α-ketoaldehydes by new a DMSO-NaBr-H2SO4 oxidation system in yields up to 90% within a short reaction time of 8-10 min. The subsequent stages of ATCN preparation are realized in aqueous media without use of any toxic solvents, in accordance with principle 5 of "green chemistry". Lithium, sodium, potassium, rubidium, and cesium 2-benzoyl-1,1,3,3-tetracyanopropenides were characterized by X-ray diffraction analysis. These salts show a good potential for synthesis of five- and six-membered heterocycles and may serve as potentially useful ligands in coordination and supramolecular chemistry.
- Karpov, Sergey V.,Grigor'Ev, Arthur A.,Kayukov, Yakov S.,Karpova, Irina V.,Nasakin, Oleg E.,Tafeenko, Victor A.
-
p. 6402 - 6408
(2016/08/16)
-
- Metal free one-pot synthesis of α-ketoamides from terminal alkenes
-
A practical approach towards the synthesis of α-ketoamides from readily available terminal alkenes (styrenes) has been developed. Use of inexpensive I2/2-iodoxybenzoic acid (IBX) in dimethyl sulphoxide (DMSO) as an oxidant under metal free one-pot conditions makes this methodology versatile.
- Dutta, Sayan,Kotha, Surya Srinivas,Sekar, Govindasamy
-
p. 47265 - 47269
(2015/06/16)
-
- Two efficient one-pot approaches for regioselective synthesis of new 3-arylpyridazino[4,3-c]quinolin-5(6H)-ones
-
Two efficient regioselective approaches for the one-pot synthesis of 3-arylpyridazino[4,3-c]quinolin-5(6H)-one derivatives are reported, by the three-component reaction of arylglyoxal monohydrates, quinoline-2,4-diol, and hydrazinium dihydrochloride or hydrazine hydrate in ethanol and pyridine. In ethanol, the reactions were catalyzed by 1,4-diazobicyclo[2,2,2]octane. The features of both procedures are high regioselectivity, mild reaction conditions, good to high yields, and operational simplicity.
- Rimaz, Mehdi
-
p. 1529 - 1534
(2015/10/20)
-
- Regiospecific one-pot, combinatorial synthesis of new substituted pyrimido[4,5-c]pyridazines as potential monoamine oxidase inhibitors
-
New 3-aryl-6-methylpyrimido[4,5-c]pyridazine-5,7(6H ,8H)-diones and 3-aryl-6-ethyl-7-thioxo-7,8-dihydropyrimido[4,5- c]pyridazin-5(6H)-ones were efficiently synthesized via a regiospecific one-pot reaction of N -methylbarbituric acid and N -ethyl-2-thiobarbituric acid with various arylglyoxal monohydrates in the presence of hydrazine dihydrochloride in ethanol at 50°C. The target compounds were obtained in high yields and were regioisomerically pure after recrystallization. These new heterocycles may act as potential MAOB inhibitors.
- Rimaz, Mehdi,Pourhossein, Paria,Khalili, Behzad
-
p. 244 - 254
(2015/05/27)
-
- One-pot three-component reactions of methyl ketones, phenols and a nucleophile: An expedient way to synthesize densely substituted benzofurans
-
Three-component reactions of phenylglyoxal monohydrate, phenols, and indoles were developed with the aid of acid-catalyst, which produced various densely substituted benzofurans with good to excellent yields. On the basis of this observation, a one-pot, step-wise reaction was developed by using methyl ketones instead of using phenylglyoxal component in I2/DMSO system. At last, three-component reaction offered a useful way to synthesize densely substituted benzofurans starting from simple and easily available substrates. The indole component can be replaced by some other nucleophiles, such as 1,2,4-trimethoxybenzene and thiophenol.
- Cheng, Cheng,Liu, Changhui,Gu, Yanlong
-
p. 8009 - 8017
(2015/12/31)
-
- PYRIDOPYRAZINES AS ANTICANCER AGENTS
-
The present invention relates to pyridopyrazine derivatives and solvates, hydrates and pharmaceutically acceptable salts thereof, the use of them in the prevention and/or the treatment of cancer diseases, as well as pharmaceutical compositions containing at least one of them as pharmaceutically active agent(s) together with pharmaceutically acceptable carrier, excipient and/or diluents, especially for the prevention and/or treatment of cancer diseases.˙
- -
-
Page/Page column 13
(2014/07/22)
-
- Unexplored reactivity of 2-oxoaldehydes towards Pictet-Spengler conditions: Concise approach to β-carboline based marine natural products
-
Novel reactions under Pictet-Spengler conditions between tryptophan methyl ester/tryptamine and 2-oxoaldehydes have been developed and successfully utilized for the total synthesis of Merinacarboline (A and B), Eudistomin Y1, Pityriacitrin B, Pityriacitrin, Fascaplysin and analogues.
- Battini, Narsaiah,Padala, Anil K.,Mupparapu, Nagaraju,Vishwakarma, Ram A.,Ahmed, Qazi Naveed
-
p. 26258 - 26263
(2014/07/08)
-
- Iodine-mediated oxidative annulation for one-pot synthesis of pyrazines and quinoxalines using a multipathway coupled domino strategy
-
An efficient iodine-mediated oxidative annulation of aryl acetylenes-arylethenes-aromatic ketones with 1,2-diamines for the synthesis of pyrazines and regioselective synthesis of quinoxalines is presented. A multipathway coupled domino approach has been developed for the one-pot synthesis of 1,4-diazines with high functional group compatibility.
- Viswanadham, K. K. Durga Rao,Prathap Reddy, Muktapuram,Sathyanarayana, Pochampalli,Ravi, Owk,Kant, Ruchir,Bathula, Surendar Reddy
-
supporting information
p. 13517 - 13520
(2015/01/09)
-
- Gold(I)-catalyzed diastereoselective hydroacylation of terminal alkynes with glyoxals
-
The reaction of an α-ketoaldehyde and a terminal alkyne in the presence of piperidine and a catalytic amount of AuCl delivers 1,2-dicarbonyl-3-enes, products of the formal hydroacylation of the triple bond. The scope of the method is broad; different aryl substituents on the dicarbonyl unit and on the alkyne are well tolerated. The products can be transformed selectively into vinylquinoxalines. Mechanistic studies, including isotope-labeling experiments, indicate that after an initial A3-type conversion to propargylic amines, a subsequent base-mediated alkyne-to-allene isomerization and a hydrolysis of the enamine substructure during the workup deliver the formal hydroacylation products. The simple AuCl catalyst and piperidine convert terminal alkynes and α-ketoaldehydes into 1,2-dicarbonyl-3-enes, the products of a formal hydroacylation of the triple bond, with excellent regio- and diastereoselectivity. There is no evidence for classical A3 coupling products, which could be expected from such a gold-catalyzed reaction of an aldehyde, an amine, and a terminal alkyne. Copyright
- Shi, Shuai,Wang, Tao,Weingand, Vanessa,Rudolph, Matthias,Hashmi, A. Stephen K.
-
supporting information
p. 1148 - 1151
(2014/03/21)
-
- Three-step synthesis of novel 2-aryl-3-benzamidobenzofurans: Regiospecific reactions catalyzed by molybdate sulfuric acid
-
A solvent-free and synthetic pathway to novel benzofuran derivatives, starting from oxidation of phenyl ketones to arylglyoxals in three steps was developed. The molybdate sulfuric acid catalyzed the reaction of arylglyoxals with benzamide and phenols to afford 2-aryl-3-benzamidobenzofurans in high yield. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, 1H NMR, and 13C NMR spectral data. The present methodology offers several advantages such as non-hazardous reaction condition, simple operation, and work-up procedure.
- Hashemi, Fatemeh,Karami, Bahador,Khodabakhshi, Saeed
-
p. 322 - 326
(2014/04/17)
-
- A convenient and mild synthesis of new 2-aryl-3-hydroxy-6,7-dihydro-1H- indol-4(5H)-ones via a one-pot, three-component reaction in water
-
A simple and convenient synthesis of 2-aryl-3-hydroxy-6,7-dihydro-1H-indol- 4(5H)-ones is achieved in high yields via the one-pot, three-component reaction of arylglyoxals, 1,3-cyclohexanedione, and ammonium acetate in water under reflux conditions.
- Khalafy, Jabbar,Etivand, Nasser,Dilmaghani, Shadi,Ezzati, Mahnaz,Marjani, Ahmad Poursattar
-
p. 3781 - 3783
(2014/07/07)
-
- Quinoxaline derivatives: Novel and selective butyrylcholinesterase inhibitors
-
Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against achymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0μM) and 7 (IC50 = 9.7 ± 0.9 μM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 μM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.
- Zeb, Aurang,Hameed, Abdul,Khan, Latifullah,Khan, Imran,Dalvandi, Kourosh,Choudhary, M. Iqbal,Basha, Fatima Z.
-
p. 724 - 729
(2015/04/14)
-
- Asymmetric Hydrogenation of 2-Aryl-5,6-dihydropyrazine Derivatives with Chiral Cationic Ruthenium Diamine Catalysts
-
The first asymmetric hydrogenation of unfunctionalized 2-substituted and 2,3-disubstituted 5,6-dihydropyrazines catalyzed by chiral cationic Ru-diamine complex (R,R)-1a was developed, affording chiral piperazine derivatives with good enantioselectivities (up to 89% ee).
- Li, Yong,He, Yanmei,Chen, Fei,Fan, Qinghua
-
supporting information
p. 991 - 994
(2016/02/18)
-
- [1,2,4]TRIAZOLO[4,3-B][1,2,4]TRIAZINE COMPOUND, PREPARATION METHOD AND USE THEREOF
-
The present invention relates to a structurally novel [1,2,4]triazolo[4,3-b][1,2,4]triazine compounds represented by formula (I) or formula (II), pharmaceutically acceptable salts thereof, prodrugs thereof, hydrates or solvates thereof, and also relates to a preparation method of the compounds, a pharmaceutical composition comprising a therapeutically effective amount of the compounds, as well as the use thereof as protein tyrosine kinase inhibitors, particularly as c-Met inhibitors, in the preparation of medicaments for the prevention and/or treatment of diseases associated with c-Met abnormality.
- -
-
Paragraph 0335; 0336
(2013/11/05)
-
- Design and synthesis of 2-acylbenzothiazoles via in situ cross-trapping strategy from benzothiazoles with aryl ketones
-
An I2/KOH synergistically promoted direct ring-opening aroylation of benzothiazoles with aryl ketones has been discovered. Aryl ketones were seen to act as carbonyl sources to construct 2-acylbenzothiazoles. This reaction could provide an example for the convergent integration of self-labor domino sequences based on an in situ cross-trapping strategy.
- Gao, Qinghe,Wu, Xia,Jia, Fengcheng,Liu, Meicai,Zhu, Yanping,Cai, Qun,Wu, Anxin
-
p. 2792 - 2797
(2013/04/24)
-
- Oxidation of aryl and heteroaryl methyl ketone to aryl and heteroarylglyoxals by using CuCl2-DMSO
-
The oxidation of aryl methyl ketone and heteroaryl methyl ketone to arylglyoxals and heteroaryl glyoxal respectively has been carried out by using the cheap and easily available, non toxic, Lewis acid CuCl2 in DMSO solvent at 70-80°C within 1-2 hr. The reaction can be performed in air without loss of variety of oxidisable fuctional group like phenolic OH, hetroaryl ring, aryl substituted methyl, halo, nitro group, etc.
- Lokhande, Pradeep D.,Waghmare, Smita R.,Gaikwad, Harsh,Hankare
-
p. 300 - 305
(2013/05/08)
-