1076-95-5Relevant articles and documents
Characterization and Synthesis of Eudistidine C, a Bioactive Marine Alkaloid with an Intriguing Molecular Scaffold
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.
, p. 10631 - 10640 (2016)
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.
Design and synthesis of coumarin-glyoxal hybrids for spermicidal and antimicrobial actions: A dual approach to contraception
Gupta, Swati,Kushwaha, Bhavana,Srivastava, Akansha,Maikhuri, Jagdamba Prasad,Sankhwar, Satya N.,Gupta, Gopal,Dwivedi, Anil Kumar
, p. 76288 - 76297 (2016)
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.
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
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.
, p. 5569 - 5575 (2015)
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.
Synthesis of α-keto aldehydes via selective Cu(i)-catalyzed oxidation of α-hydroxy ketones
Zheng, Shasha,Smit, Wietse,Spannenberg, Anke,Tin, Sergey,de Vries, Johannes G.
supporting information, p. 4639 - 4642 (2022/04/19)
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.
A novel class for carbonic anhydrases inhibitors and evaluation of their non-zinc binding
Kuzu, Burak,Tan, Meltem,Gül?in, ?lhami,Menges, Nurettin
, (2021/06/09)
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.
Ynonylation of Acyl Radicals by Electroinduced Homolysis of 4-Acyl-1,4-dihydropyridines
Luo, Xiaosheng,Wang, Ping
supporting information, p. 4960 - 4965 (2021/07/20)
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.
Catalytic Asymmetric Darzens-Type Epoxidation of Diazoesters: Highly Enantioselective Synthesis of Trisubstituted Epoxides
Jeong, Hye-Min,Nam, Dong Guk,Ryu, Do Hyun,Shim, Su Yong
supporting information, p. 22236 - 22240 (2021/09/13)
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.
One-pot multi-component synthesis of novel chromeno[4,3-b]pyrrol-3-yl derivatives as alpha-glucosidase inhibitors
Faramarzi, Mohammad Ali,Hasaninejad, Alireza,Iraji, Aida,Karami, Malihe,Mahdavi, Hossein,Mahdavi, Mohammad,Mojtabavi, Somayeh
, (2021/10/29)
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.
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
Liao, Shengrong,Lin, Xiuping,Liu, Yonghong,Wang, Junfeng,Xu, Huayan,Yang, Bin,Zhou, Xuefeng
, p. 8735 - 8739 (2021/10/22)
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.
Synthesis and solid-state luminescence of highly-substituted 6-amino-2H-pyran-2-one derivatives
Karpov, Sergey,Kayukov, Yakov,Grigor'ev, Arthur,Nasakin, Oleg,Kayukova, Olga,Tafeenko, Viktor
, (2020/06/04)
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.
