- Construction of indole and benzofuran systems on the solid phase via palladium-mediated cyclizations
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Molecular diversity in the area of nonpeptide, small organic molecules has been receiving considerable attention in the chemical community. Herein, we report new solid-phase methodology for the rapid generation of such small-molecule libraries by simultaneous-parallel or combinatorial synthesis. We have adapted a palladium-mediated, intramolecular Heck-type reaction, a mild and versatile method for carbon-carbon bond formation, to the solid phase. This has been applied to the synthesis of diverse indole and benzofuran derivatives, such as 8, 15, and 28, in good to excellent yields.
- Zhang, Han-Cheng,Maryanoff, Bruce E.
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- Development of a peptidomimetic ligand for efficient isolation and purification of factor VIII via affinity chromatography
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Hemophilia A, one of the most severe bleeding disorders, results from an inherited deficiency of factor VIII (FVIII) function. Treatment by injection of FVIII has been a common procedure for decades. Nevertheless, the production and purification of FVIII remains a challenging task. Current procedures using immunoaffinity chromatography are expensive and suffer from the instability of the applied antibody ligands, which elute along with the product and contaminate it. Recently, FVIII was purified by use of octapeptide ligands, but their low protease-resistance limits their application. We here report the systematic rational and combinatorial optimization procedure that allowed us to transfer the octapeptide ligands into a small peptidomimetic. This compound is the smallest ligand known for separation of such a large protein (330 kDa). It not only binds and purifies FVIII with high efficiency but also is stable, protease-resistant, and cheap to produce in preparative scale. Hence it offers a valuable alternative to antibody-based purification procedures.
- Kn?r, Sebastian,Khrenov, Alexey V.,Laufer, Burkhardt,Saenko, Evgueni L.,Hauser, Charlotte A. E.,Kessler, Horst
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- Reconsidering the Structure of Serlyticin-A
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Serlyticin-A is a secondary metabolite first isolated from a culture of Serratia ureilytica grown using squid pen as the sole carbon/nitrogen source. A previous study by Kuo et al. demonstrated that it has antioxidative and antiproliferative properties. However, the proposed chemical structure of serlyticin-A is likely incorrect based on the thermodynamic instability of its three contiguous heteroatom-heteroatom bonds. Here, we use quantum chemical calculations to predict 1H and 13C chemical shifts for serlyticin-A and demonstrate a discrepancy between the calculated and experimental chemical shifts. We then propose several reasonable alternative structures for serlyticin-A. Considering the known antioxidant and antiproliferative activity of hydroxamic acids as well as their stability and prevalence in natural products of bacterial origin, we believe that serlyticin-A is most likely 3-indolylacetohydroxamic acid (4). We provide our rationale for this assignment as well as experimental data for pure 3-indolylacetohydroxamic acid obtained via de novo synthesis. This study highlights the power of computational NMR shift prediction to revise chemical structures for natural products like serlyticin-A.
- Tsui, Ka Yi,Tombari, Robert J.,Olson, David E.,Tantillo, Dean J.
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- Reaction of methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with ureas: Facile entry into the polycyclic meridianin analogues with uracil structural unit
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Methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate was prepared simply and efficiently in two steps from 3-indoleacetic acid employing N,N-dimethylformamide dimethylacetal (DMFDMA). Upon treatment of (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with various (thio)ureas in the presence of an acid 2-(1H-indol-3-yl)-3-(3-substituted(thio)ureido) propenoates were obtained in high yields. A base promoted cyclization of these (thio)ureidopropenoate derivatives afforded 5-(indol-3-yl)-3-substituted- pyrimidine-2,4-diones which represent a new family of meridianine analogues.
- ?asar, Zdenko,Bevk, David,Svete, Jurij,Stanovnik, Branko
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- Metabolism of indole-3-acetic acid in rice: Identification and characterization of N-β-d-glucopyranosyl indole-3-acetic acid and its conjugates
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A search was made for conjugates of indole-3-acetic acid (IAA) in rice (Oryza sativa) using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) in order to elucidate unknown metabolic pathways for IAA. N-β-d-Glucopyranosyl indole-3-acetic acid (IAA-N-Glc) was found in an alkaline hydrolysate of rice extract. A quantitative analysis of 3-week-old rice demonstrated that the total amount of IAA-N-Glc was equal to that of IAA. A LC-ESI-MS/MS-based analysis established that the major part of IAA-N-Glc was present as bound forms with aspartate and glutamate. Their levels were in good agreement with the total amount of IAA-N-Glc during the vegetative growth of rice. Further detailed analysis showed that both conjugates highly accumulated in the root. The free form of IAA-N-Glc accounted for 60% of the total in seeds but could not be detected in the vegetative tissue. An incorporation study using deuterium-labeled compounds showed that the amino acid conjugates of IAA-N-Glc were biosynthesized from IAA-amino acids. IAA-N-Glc and/or its conjugates were also found in extracts of Arabidopsis, Lotus japonicus, and maize, suggesting that N-glucosylation of indole can be the common metabolic pathway of IAA in plants.
- Kai, Kenji,Wakasa, Kyo,Miyagawa, Hisashi
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- QUANTIFICATION OF INDOL-3-YL ACETIC ACID IN PEA AND MAIZE SEEDLINGS BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY
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A procedure is described for the identification and quantification of IAA in plant tissues by GC/MS analysis of the N-heptafluorobutyryl ethyl ester of IAA using IAA as an internal standard.The detection limit is ca. 3 pmol IAA/tissue sample.By using this method, IAA levels of 30-90 pmol/g fr. wt were obtained for dark-grown Pisum sativum epicotyls and 71-199 pmol/g fr. wt for dark-grown Zea mays seedlings.When either methanol or ethanol was used as extraction solvent, some esterification of IAA during sample preparation was observed.No evidence for the natural occurence of methyl or ethyl esters of IAA in Pisum sativum seedlings was found.Key Word Index-Pisum sativum; Zea mays; Leguminosae; Gramineae; hormone; indol-2-yl acetic acid; GC/MS; deuterium label.
- Allen, James R. F.,Rivier, Laurent,Pilet, Paul-Emile
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- Marine-inspired bis-indoles possessing antiproliferative activity against breast cancer; design, synthesis, and biological evaluation
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Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a-f and 9a-h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 μM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%-58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.
- Eldehna, Wagdy M.,Hassan, Ghada S.,Al-Rashood, Sara T.,Alkahtani, Hamad M.,Almehizia, Abdulrahman A.,Al-Ansary, Ghada H.
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- Discovery of an indole-substituted furanone with tubulin polymerization inhibition activity
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Analogs of diarylpyrrolinone lead compound 1 were prepared and tested for anti-proliferative activity in U-937 cancer cells. Alterations of 1 focused on modifying the two nitrogen atoms: a) the pyrrolinone nitrogen atom was substituted with a propyl group or replaced with an oxygen atom (furanone), and b) the substituents on the indole nitrogen were varied. These changes led to the discovery of a furanone analog 3b with sub-micromolar anti-cancer potency and tubulin polymerization inhibition activity.
- Mowery, Patricia,Filkorn, Madison M.,Hurysz, Brianna,Kwansare, Deborah O.,Lafferty, Megan M.,McFadden, Marissa A.,Neerukonda, Namita D.,Patel, Roslyn R.,Pierce, Kelsey,Sockett, Kaitlynn A.,Truax, Nathanyal J.,Webster, Nathan R.,Pelkey, Erin T.
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- Molecular cloning and biochemical characterization of indole-3-acetic acid methyltransferase from poplar
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Indole-3-acetic acid (IAA) is the most active endogenous auxin and is involved in various physiological processes in higher plants. Concentrations of IAA in plant tissues are regulated at multiple levels including de novo biosynthesis, conjugation/deconjugation, and degradation. In this paper, we report molecular isolation and biochemical characterization of a gene PtIAMT1 from poplar encoding IAA methyltransferase (IAMT), which plays a role in regulating IAA homeostasis. PtIAMT1 was identified from the poplar genome based on sequence similarity to Arabidopsis IAMT. A full-length cDNA of PtIAMT1 was cloned from poplar roots via RT-PCR. Recombinant PtIAMT1 expressed in Escherichia coli was purified to electrophoretic homogeneity. Enzyme assays combined with GC-MS verified that PtIAMT1 catalyzes formation of methyl indole-3-acetate using S-adenosyl-l-methionine (SAM) as a methyl donor and IAA as a methyl acceptor. PtIAMT1 had a temperature optimum at 25 °C and a pH optimum at pH 7.5. Its activity was promoted by K+ but inhibited by Fe2+, Cu2+ and Zn2+. Under steady-state conditions, PtIAMT1 exhibited apparent Km values of 23.1 μM and 30.4 μM for IAA and SAM, respectively. Gene expression analysis showed that PtIAMT1 had the highest level of expression in stems, a moderate level of expression in young leaves, and a low level of expression in roots. Presence of PtIAMT1 transcripts in several organs suggests that PtIAMT1 is involved in development of multiple organs in poplar.
- Zhao, Nan,Guan, Ju,Lin, Hong,Chen, Feng
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- Etude spectroscopique (IR, RMN1H, masse) comparee des acides indolyl-1 acetique (AIA-1) indolyl-2 acetique (AIA-2) et indolyl-3 acetique (AIA-3) et de leurs esters methyliques (masse)
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Spectroscopic study (i.r., PMR) of 1-indolyl, 2-indolyl and 3-indolyl acetic acids points out structural differences.Conventional mass spectra of the three acids or their methyl esters are very similar.Use of the MIKE and CID-MIKE techniques on the molecular ion allows an easy discrimination of each methylic ester of the three acids.
- Vebrel, Joel,Laude, Bernard,Seguin, Alain,Dubouchet, Jacques
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- Pyridopyrimidinone intermediate ionic derivative containing indole units, and preparation method and application thereof
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The invention relates to a pyridopyrimidinone intermediate ion derivative containing indole units as well as a preparation method and application thereof. The compound has the following formula (I), has excellent insecticidal activity on white back planthoppers and broad bean aphids and the like, and can be used for preventing and treating rice planthoppers. Medicament or medicament for injurious insects such as aphids and the like. The structure and the preparation process are simple, and the production cost is low.
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Paragraph 0047; 0050; 0051
(2021/08/25)
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- Convenient synthesis of long alkyl-chain triazolylglycosides using ionic liquid as dual promoter-solvent: Readily access to non-ionic triazolylglycoside surfactants for evaluation of cytotoxic activity
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A convenient method for the one-pot synthesis of long alkyl-chain triazolylglycosides using ionic liquid as dual promoter and solvent is described via a sequential one-pot two-step glycosidation-CuAAc click reaction. The reaction was carried out using commercially available substrates, including glycosyl bromides, sodium azide and various long alkyl-chain alkynes to achieve the corresponding products in moderate to high yields. Furthermore, this approach was successfully applied for the preparation of non-ionic monocatenary triazolylglycoside surfactants in excellent yields through simple deacetylation. Subsequently, these surfactants were further evaluated for their cytotoxic activity.
- Ketsomboon, Nutthanicha,Saeeng, Rungnapha,Sirion, Uthaiwan,Srisook, Klaokwan
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- Identification of organophosphorus simulants for the development of next-generation detection technologies
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Organophosphorus (OP) chemical warfare agents (CWAs) represent an ongoing threat but the understandable widespread prohibition of their use places limitations on the development of technologies to counter the effects of any OP CWA release. Herein, we describe new, accessible methods for the identification of appropriate molecular simulants to mimic the hydrogen bond accepting capacity of the PO moiety, common to every member of this class of CWAs. Using the predictive methodologies developed herein, we have identified OP CWA hydrogen bond acceptor simulants for soman and sarin. It is hoped that the effective use of these physical property specific simulants will aid future countermeasure developments.
- Ellaby, Rebecca J.,Clark, Ewan R.,Allen, Nyasha,Taylor, Faith R.,Ng, Kendrick K. L.,Dimitrovski, Milan,Chu, Dominique F.,Mulvihill, Daniel P.,Hiscock, Jennifer R.
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p. 2008 - 2014
(2021/03/16)
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- Fe-catalyzed Fukuyama-type indole synthesis triggered by hydrogen atom transfer
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Fe, Co, and Mn hydride-initiated radical olefin additions have enjoyed great success in modern synthesis, yet the extension of other hydrogen radicalophiles instead of olefins remains largely elusive. Herein, we report an efficient Fe-catalyzed intramolec
- Huang, Hanmin,Yu, Min,Zhang, Tianze
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p. 10501 - 10505
(2021/08/20)
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- Design, synthesis and biological evaluation of pyrazolo[3,4-d]pyrimidine-based protein kinase D inhibitors
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The multiple roles of protein kinase D (PKD) in various cancer hallmarks have been repeatedly reported. Therefore, the search for novel PKD inhibitors and their evaluation as antitumor agents has gained considerable attention. In this work, novel pyrazolo[3,4-d]pyrimidine based pan-PKD inhibitors with structural variety at position 1 were synthesized and evaluated for biological activity. Starting from 3-IN-PP1, a known PKD inhibitor with IC50 values in the range of 94–108 nM, compound 17m was identified with an improved biochemical inhibitory activity against PKD (IC50 = 17–35 nM). Subsequent cellular assays demonstrated that 3-IN-PP1 and 17m inhibited PKD-dependent cortactin phosphorylation. Furthermore, 3-IN-PP1 displayed potent anti-proliferative activity against PANC-1 cells. Finally, a screening against different cancer cell lines demonstrated that 3-IN-PP1 is a potent and versatile antitumoral agent.
- Gilles, Philippe,Kashyap, Rudra S.,Freitas, Maria Jo?o,Ceusters, Sam,Van Asch, Koen,Janssens, Anke,De Jonghe, Steven,Persoons, Leentje,Cobbaut, Mathias,Daelemans, Dirk,Van Lint, Johan,Voet, Arnout R.D.,De Borggraeve, Wim M.
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supporting information
(2020/08/25)
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- Enantioselective Syntheses of Strychnos and Chelidonium Alkaloids through Regio- and Stereocontrolled Cooperative Catalysis
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We describe enantioselective syntheses of strychnos and chelidonium alkaloids. In the first case, indole acetic acid esters were established as excellent partner nucleophiles for enantioselective cooperative isothiourea/Pd catalyzed α-alkylation. This provides products containing indole-bearing stereocenters in high yield and with excellent levels of enantioinduction in a manner that is notably independent of the N-substituent. This led to concise syntheses of (?)-akuammicine and (?)-strychnine. In the second case, the poor performance of ortho-substituted cinnamyl electrophiles in the enantioselective cooperative isothiourea/Ir catalyzed α-alkylation was overcome by appropriate substituent choice, leading to enantioselective syntheses of (+)-chelidonine, (+)-norchelidonine, and (+)-chelamine.
- Fyfe, James W. B.,Hutchings-Goetz, Luke S.,Snaddon, Thomas N.,Yang, Chao
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supporting information
p. 17556 - 17564
(2020/08/14)
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- Carbamoyl Fluoride-Enabled Enantioselective Ni-Catalyzed Carbocarbamoylation of Unactivated Alkenes
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A carbamoyl fluoride-enabled enantioselective Ni-catalyzed carbocarbamoylation of unactivated alkenes was developed, providing a broad range of chiral γ-lactams bearing an all-carbon quaternary center in 45-96% yield and 38-97% ee.
- Li, Yue,Luan, Yu-Xin,Qi, Shao-Long,Wang, Rong-Hua,Ye, Mengchun,Zhang, Feng-Ping
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supporting information
p. 19844 - 19849
(2021/01/01)
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- Role of Arabidopsis INDOLE-3-ACETIC ACID CARBOXYL METHYLTRANSFERASE 1 in auxin metabolism
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The phytohormone auxin regulates a wide range of developmental processes in plants. Indole-3-acetic acid (IAA) is the main auxin that moves in a polar manner and forms concentration gradients, whereas phenylacetic acid (PAA), another natural auxin, does not exhibit polar movement. Although these auxins occur widely in plants, the differences between IAA and PAA metabolism remain largely unknown. In this study, we investigated the role of Arabidopsis IAA CARBOXYL METHYLTRANSFERASE 1 (IAMT1) in IAA and PAA metabolism. IAMT1 proteins expressed in Escherichia coli could convert both IAA and PAA to their respective methyl esters. Overexpression of IAMT1 caused severe auxin-deficient phenotypes and reduced the levels of IAA, but not PAA, in the root tips of Arabidopsis, suggesting that IAMT1 exclusively metabolizes IAA in vivo. We generated iamt1 null mutants via CRISPR/Cas9-mediated genome editing and found that the single knockout mutants had normal auxin levels and did not exhibit visibly altered phenotypes. These results suggest that other proteins, namely the IAMT1 homologs in the SABATH family of carboxyl methyltransferases, may also regulate IAA levels in Arabidopsis.
- Takubo, Eiko,Kobayashi, Makoto,Hirai, Shoko,Aoi, Yuki,Ge, Chennan,Dai, Xinhua,Fukui, Kosuke,Hayashi, Ken-ichiro,Zhao, Yunde,Kasahara, Hiroyuki
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p. 1033 - 1038
(2020/05/22)
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- Agent for Preventing or Ameliorating Hearing Impairment
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It is to provide an agent for preventing or improving hearing loss, which comprises a low molecular compound which can be produced relatively easily and inexpensively as an active ingredient. One or more compounds selected from the group consisting of compounds represented by the following formulas (I0), (II), and (III) and a pharmaceutically acceptable salt of the compounds when R3 is OH are used as an agent for preventing or improving hearing loss.
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Paragraph 0093; 0094; 0112-0113
(2019/08/02)
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- 1,3-Dibromo-5,5-dimethylhydantoin as a Precatalyst for Activation of Carbonyl Functionality
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Activation of carbonyl moiety is one of the most rudimentary approaches in organic synthesis and is crucial for a plethora of industrial-scale condensation reactions. In esterification and aldol condensation, which represent two of the most important reactions, the susceptibility of the carbonyl group to nucleophile attack allows the construction of a variety of useful organic compounds. In this context, there is a constant need for development of and improvement in the methods for addition-elimination reactions via activation of carbonyl functionality. In this paper, an advanced methodology for the direct esterification of carboxylic acids and alcohols, and for aldol condensation of aldehydes using widely available, inexpensive, and metal-free 1,3-dibromo-5,5-dimethylhydantoin under neat reaction conditions is reported. The method is air- and moisture-tolerant, allowing simple synthetic and isolation procedures for both reactions presented in this paper. The reaction pathway for esterification is proposed and a scale-up of certain industrially important derivatives is performed.
- ?ebular, Klara,Bo?i?, Bojan ?.,Stavber, Stojan
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supporting information
(2019/08/01)
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- Esterification of aryl/alkyl acids catalysed by n-bromosuccinimide under mild reaction conditions
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N-halosuccinimides (NXSs) are well-known to be convenient, easily manipulable and low-priced halogenation reagents in organic synthesis. In the present work, N-bromosuccinimide (NBS) has been promoted as the most efficient and selective catalyst among the NXSs in the reaction of direct esterification of aryl and alkyl carboxylic acids. Comprehensive esterification of substituted benzoic acids, mono-, di- and tri-carboxy alkyl derivatives has been performed under neat reaction conditions. The method is metal-free, air- and moisture-tolerant, allowing for a simple synthetic and isolation procedure as well as the large-scale synthesis of aromatic and alkyl esters with yields up to 100%. Protocol for the recycling of the catalyst has been proposed.
- ?ebular, Klara,Bo?i?, Bojan ?.,Stavber, Stojan
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- Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity
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Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be used to pull down active endogenous KLK6.
- De Vita, Elena,Schüler, Peter,Lovell, Scott,Lohbeck, Jasmin,Kullmann, Sven,Rabinovich, Eitan,Sananes, Amiram,He?ling, Bernd,Hamon, Veronique,Papo, Niv,Hess, Jochen,Tate, Edward W.,Gunkel, Nikolas,Miller, Aubry K.
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supporting information
p. 8859 - 8874
(2018/10/09)
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- Efficient synthesis of organic thioacetates in water
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Thioacetates as precursors of thiols are interesting starting points for synthesizing other organosulfur compounds. Herein, we propose a simple, efficient and fast method to obtain organic thioacetates using water as a solvent. Taking into account the great attention that has been paid toward environmentally friendly synthetic procedures in the past decades, we prove the role and the strength of the thioacetate anion as a nucleophile for nucleophilic displacement reactions in an aqueous medium. The reactions were carried out under pH control, to prevent the decomposition of the mesylate starting materials, using potassium carbonate as a safe and mild base. A simple work up allows products to be obtained with excellent yield and acceptable purity.
- Olivito,Costanzo,Di Gioia,Nardi,Oliverio,Procopio
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supporting information
p. 7753 - 7759
(2018/11/02)
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- FUSED THIAZOLOPYRIMIDINE DERIVATIVES AS MNKS INHIBITORS
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The present invention relates to compounds of formulae I and H, or pharmaceutically acceptable salts or esters thereof. Further aspects of the invention relate to pharmaceutical compositions and therapeutic uses of said compounds in the treatment of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, inappropriate cellular inflammatory responses, or neurodegenerative disorders, preferably tauopathies, even more preferably, Alzheimer's disease.
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Page/Page column 78; 79
(2017/06/12)
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- Development and Application of a Recyclable High-Load Magnetic Co/C Hybrid ROMP-Derived Benzenesulfonyl Chloride Reagent and Utility of Corresponding Analogues
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The development and application of high-load, recyclable magnetic Co/C hybrid ROMP-derived benzenesulfonyl chloride and analogues is reported. The regeneration and utility of these reagents in the methylation/alkylation of various carboxylic acids is demonstrated via efficient retrieval of the magnetic reagent with a neodymium magnet. Additional reactions employing the analogue sulfonic acid and in situ generated magnetic benzenesulfonyl azide are also reported.
- Faisal, Saqib,Zang, Qin,Maity, Pradip K.,Brandhofer, Agnes,Kearney, Patrick C.,Reiser, Oliver,Grass, Robert N.,Stoianova, Diana,Hanson, Paul R.
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supporting information
p. 2274 - 2277
(2017/05/12)
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- A double-indole hydrazone compound and use thereof
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The invention provides a bisindole acylhydrazone compound shown as the formula I or salt, hydrate or crystals, accepted in the pharmacy, of the bisindole acylhydrazone compound. According to the bisindole acylhydrazone compound, R does not exist or is selected from alkylene of C1-5. The bisindole acylhydrazone compound has a certain antibacterial activity, and can serve as potential antibiotics or a daily chemical product. What is beyond the expectation is that compounds 4e-4h and compounds 4a-4c are quite similar in structure, the antibacterial activity of the compounds 4e-4h and the antibacterial activity of the compounds 4a-4c are obviously better than that of other compounds, particularly, the activity of the compound 4h is best and is remarkably better than that of compounds 4e-4g. The formula I is shown in the specification.
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Paragraph 0036; 0039-0040
(2017/10/06)
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- Indole hydrazone compounds
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The invention provides a compound of the formula I as shown in the description. In the formula, R is connected with the carbon atom at the 2nd or 3rd site of indolyl and is selected from none or C1-3 alkylene. Molecular tweezers of bisindole acylhydrazone have a good recognition cooperation function on inspected malic acid, tartaric acid, ascorbic acid and tryptophan, and have no recognition cooperation function on other inspected organic acids such as lactic acid, oxalic acid, tyrosine, histidine and serine. Therefore, due to the selective recognition property of a molecular tweezers receptor has the potential to be applied to fields such as analysis and separation of relevant organic acids in biological medicines, and transportation of organic acid medicines.
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Paragraph 0039-0042
(2017/11/17)
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- C3-CARBON LINKED GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 303
(2017/12/05)
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- The "gatekeeper" Residue Influences the Mode of Binding of Acetyl Indoles to Bromodomains
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Small-molecule hits for the bromodomains of CREBBP and BAZ2B have been identified by scaffold hopping followed by docking of a set of ~200 compounds containing the acetyl indole scaffold. Chemical synthesis of nearly 30 derivatives has resulted in ligands of representatives of three subfamilies of human bromodomains with favorable ligand efficiency. The X-ray crystal structures of three different bromodomains (CREBBP, BAZ2B, and BRPF1b) in complex with acetyl indole derivatives reveal the influence of the gatekeeper residue on the orientation of small-molecule ligands in the acetyl lysine binding site.
- Unzue, Andrea,Zhao, Hongtao,Lolli, Graziano,Dong, Jing,Zhu, Jian,Zechner, Melanie,Dolbois, Aymeric,Caflisch, Amedeo,Nevado, Cristina
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p. 3087 - 3097
(2016/05/19)
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- N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound and preparation method and application thereof
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The invention provides a N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound and a preparation method and application thereof.The N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound has a structure shown as a formula I (please see the formula in the description) and has the obvious inhibiting effect on an HCV virus, the anti-HCV virus treatment index is higher than that of existing clinical drugs including alpha-1b(IFNalpha-1b) interferon and ribavirin, and the N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound can serve as an anti-HCV drug candidate; in addition, the preparation method is simple, high in yield and suitable for industrial production.
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Paragraph 0067
(2016/10/09)
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- Method for synthesizing azanol
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The invention relates to a hydroxylamine synthesis method. The hydroxylamine synthesis method comprises the following steps: (A) enabling alcohol to react with alkyl sulfonyl halide in the presence of an acid-binding agent to obtain sulphonate; (B) enabling the obtained sulphonate in the step (A) to react with N-hydroxycyclodiimide in the presence of alkali to generate alkylate of the N-hydroxycyclodiimide; and (C) enabling the alkylate obtained in the step (B) to react with an aminolysis reagent or a hydrazinolysis reagent to obtain the hydroxylamine. The method is high in yield and suitable for large-scale industrial hydroxylamine synthesis.
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Paragraph 0151; 0160-0164
(2016/10/08)
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- Total synthesis of N-butyl-1-deoxynojirimycin
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N-Butyl-1-deoxynojirimycin (NB-DNJ) derived from imino sugar deoxynojirimycin (DNJ) has been approved for the treatment of Gaucher’s disease. Herein, a facile and efficient synthetic procedure for NB-DNJ has been described. Comparing to the methods reported previously,methanesulfonyl group was used as a leaving group for easy displacement upon attack by the imine in the sugar ring, leading to a high yield during the introduction of the n-butyl group. Thismethod can serve as an excellent protocol for the synthesis of DNJ derivatives with a variety of N-alkyl substituents and for large-scale production.
- Wang, Jiajia,Zhao, Yunyan,Zhao, Wei,Wang, Peng,Li, Jing
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p. 445 - 454
(2017/08/23)
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- Exploiting 1,2,3-Triazolium Ionic Liquids for Synthesis of Tryptanthrin and Chemoselective Extraction of Copper(II) Ions and Histidine-Containing Peptides
-
Based on a common structural core of 4,5,6,7-Tetrahydro[1,2,3]triazolo[1,5-A]pyridine, a number of bicyclic triazolium ionic liquids 1-3 were designed and successfully prepared. In our hands, this optimized synthesis of ionic liquids 1 and 2 requires no chromatographic separation. Also in this work, ionic liquids 1, 2 were shown to be efficient ionic solvents for fast synthesis of tryptanthrin natural product. Furthermore, a new affinity ionic liquid 3 was tailor-synthesized and displayed its effectiveness in chemoselective extraction of both Cu(II) ions and, for the first time, histidine-containing peptides.
- Li, Hsin-Yi,Chen, Chien-Yuan,Cheng, Hui-Ting,Chu, Yen-Ho
-
-
- HIGH-PURITY 1-FLUOROBUTANE AND PLASMA ETCHING METHOD
-
The present invention provides: 1-fluorobutane having a purity of 99.9% by volume or more and a total butene content of 1,000 ppm by volume or less; use of the 1-fluorobutane as a dry etching gas; and a plasma etching method using the 1-fluorobutane as an etching gas. According to the present invention, high-purity 1-fluorobutane which is suitable as a plasma reaction gas for semiconductors, the use of the high-purity 1-fluorobutane as a dry etching gas, and a plasma etching method using the high-purity 1-fluorobutane as an etching gas are provided.
- -
-
Paragraph 0075-0077
(2017/01/09)
-
- Erythropoietin Expression Promoter
-
The present invention provides an erythropoietin expression-enhancing agent that can cancel the suppression of erythropoietin production or promote erythropoietin production, and a therapeutic or preventive drug for anemia, a liver function-improving agent, an ischemic injury-improving agent, a renal protective agent, and an insulin secretagogue comprising the erythropoietin expression-enhancing agent. The erythropoietin expression-enhancing agent of the present invention comprises one or more compounds selected from the group consisting of compounds represented by the following general formulas (I), (II), and (III) and pharmaceutically acceptable salts thereof when R3 is OH.
- -
-
Paragraph 0133; 0134
(2015/12/30)
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- NEW 1,2,4-OXADIAZOL DERIVATIVES, PROCESS FOR THEIR PREPARATION AND USE THEREOF AS INTERMEDIATES IN THE PREPARATION OF INDOLIC ALKALOIDS
-
The present invention relates in general terms to a variously substituted 1,2,4-oxadiazol derivative, a process for their preparation, and use thereof as an intermediate in the preparation of indolic alkaloids, including phidianidine B and A.
- -
-
Paragraph 0051
(2015/02/25)
-
- DERIVATIVES OF AZA ADAMANTANE AND USES THEREOF
-
The present invention relates to certain amide derivatives that have the ability to inhibit 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.
- -
-
Paragraph 0295; 0296
(2015/05/26)
-
- Microwave-assisted synthesis and molecular recognition properties of novel indole acylhydrazone receptors
-
Indole acylhydrazones were synthesised in high yields under microwave irradiation By using indole carboxylic acid and 1,4-benzenedialdehyde as starting materials. Their structures were characterised by 1H NMR, IR, MS spectra and elemental analysis. Selective recognition properties of these receptors have been investigated by UV-Vis spectra titration indicating that these receptors can form 1:1 supramolecular complexes with malic acid, tartaric acid, ascorbic acid and tryptophan.
- Ye, Ying,Suo, Yourui,Yang, Fang,Yang, Yongjing,Han, Lijuan
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p. 296 - 299
(2015/06/02)
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- CYCLIC AMIDE DERIVATIVES AS INHIBITORS OF 11 - BETA - HYDROXYSTEROID DEHYDROGENASE AND USES THEREOF
-
The present invention relates to certain amide derivatives that have the ability to inhibit 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.
- -
-
Paragraph 0279; 0280
(2015/06/17)
-
- Synthesis, in vitro lipoxygenase inhibition, docking study and thermal stability analyses of novel indole derivatives: Non-isothermal kinetic study of potent LOX inhibitor N'-(diphenylmethylene)-2-(1H-indole-3-yl) acetohydrazide
-
A series of indole derivatives has been synthesized and biologically evaluated to identify potent new lipoxygenase (LOX) inhibitors. All selected indole derivatives were screened for their LOX inhibition studies. Most of compounds showed good in vitro LOX inhibition properties exhibiting IC 50 values in the range of 53.61 ± 0.14 to 198.61 ± 0.11 μM (mean ± SEM), as compared to the standard inhibitor baicalein with IC50 value 22.4 ± 1.3 μM. Structure activity relationship has been discussed and docking stimulation of most active compound 4f has also performed. Thermal stability and melting point of indole derivatives have been performed by thermal gravimetric analysis and differential scanning calorimetry analysis under nitrogen atmosphere at heating rate of 20 C min-1. Compound 4f bearing bis-phenyl moiety has been found to be the most potent (IC50 53.61 ± 0.14 μM) and thermally most stable among the tested compounds. Imine (C=N) was found to be the key moiety for increasing the thermal stabilities of indole derivatives. FT-IR, NMR and elemental analysis techniques were performed for structural characterization.
- Yar, Muhammad,Sidra, Lala Rukh,Pontiki, Eleni,Mushtaq, Nafeesa,Ashraf, Muhammad,Nasar, Rumana,Khan, Islam Ullah,Mahmood, Nasir,Naqvi, Syed Ali Raza,Khan, Zulfiqar Ali,Shahzad, Sohail Anjum
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p. 369 - 378
(2014/04/03)
-
- Design and synthesis of new dual binding site cholinesterase inhibitors: In vitro inhibition studies with in silico docking
-
Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer's disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the tested compounds exhibited inhibitory activity against AChE and BChE. Among them 4f and 6e showed the highest AChE inhibitory activity with IC50 91.21±0.06 and 68.52±0.04 μM, respectively. However compound 5a exhibited the highest inhibitory activity against BChE (IC50 55.21±0.12 μM).
- Yar, Muhammad,Bajda, Marek,Mehmood, Rana Atif,Sidra, Lala Rukh,Ullah, Nisar,Shahzadi, Lubna,Ashraf, Muhammad,Ismail, Tayaba,Shahzad, Sohail Anjum,Khan, Zulfiqar Ali,Naqvi, Syed Ali Raza,Mahmood, Nasir
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p. 331 - 338
(2014/03/21)
-
- Total synthesis of asterredione
-
The first total synthesis of asterredione was efficiently accomplished over five linear steps and in 21.5% overall yield. As the crucial step, the 2-quaternary 1,3-cyclopentenedione skeleton of asterredione was readily achieved using the Darzens/ring-expansion strategy developed in our laboratory. The structure of synthesized asterredione was fully confirmed by X-ray crystallography.
- Gai, Sinan,Zhang, Qing,Hu, Xiangdong
-
supporting information
p. 2111 - 2114
(2014/04/03)
-
- Methyl salicylate as a selective methylation agent for the esterification of carboxylic acids
-
Methyl salicylate is a selective and inexpensive methylating agent for the esterification of carboxylic acids with a wide range of functional group tolerance. The intramolecular hydrogen bonds between the carboxylate and hydroxyl groups in methyl salicylate are essential for the transformation. Allyl, benzyl, methallyl, and propargyl salicylates can also be used as alkylating agents for the preparation of the corresponding alkyl carboxylates.
- Chen, Si,Jia, Lei,Li, Xiaonan,Luo, Meiming
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p. 263 - 268
(2014/03/21)
-
- NEW 1, 2, 4-OXADIAZOL DERIVATIVES, PROCESS FOR THEIR PREPARATION AND USE THEREOF AS INTERMEDIATES IN THE PREPARATION OF INDOLIC ALKALOIDS
-
The present invention relates in general terms to a variously substituted 1, 2, 4-oxadiazol derivative, a process for their preparation, and use thereof as an intermediate in the preparation of indolic alkaloids, including phidianidine B and A.
- -
-
Page/Page column 20; 21
(2013/10/08)
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- Biomimetic total syntheses of borreverine and flinderole alkaloids
-
Dimeric indole alkaloids represent a structurally unique class of natural products having interesting biological activities. Recently, we reported the first total synthesis of flinderoles B and C, structurally unique and potent antimalarial natural products. Central to the design of the approach and by virtue of a one-pot, acid-catalyzed dimerization reaction, the route also provided total synthesis of the borreverine class of natural products. This full account details the progress of efforts that culminated in the protecting-group-free, six-step total synthesis of all of the flindersia alkaloids: dimethylisoborreverine, isoborreverine, flinderoles A-C, and their analogues. A biomimetic approach featuring a scalable and catalytic formal [3 + 2] cycloaddition and Diels-Alder reaction is outlined in detail. On the basis of the experimental observations, a detailed mechanism has been proposed for the dimerization of tertiary alcohol 28.
- Dethe, Dattatraya H.,Erande, Rohan D.,Ranjan, Alok
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p. 10106 - 10120
(2013/11/06)
-
- DERIVATIVES OF AZA ADAMANTANE AND USES THEREOF
-
The present invention relates to certain amide derivatives that have the ability to inhibit 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.
- -
-
Page/Page column 87
(2013/08/15)
-
- CYCLIC AMIDE DERIVATIVES AS INHIBITORS OF 11 - BETA - HYDROXYSTEROID DEHYDROGENASE AND USES THEREOF
-
The present invention relates to certain amide derivatives that have the ability to inhibit 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and which are therefore useful in the treatment of certain disorders that can be prevented or treated by inhibition of this enzyme. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders. It is expected that the compounds of the invention will find application in the treatment of conditions such as non-insulin dependent type 2 diabetes mellitus (NIDDM), insulin resistance, obesity, impaired fasting glucose, impaired glucose tolerance, lipid disorders such as dyslipidemia, hypertension and as well as other diseases and conditions.
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Page/Page column 79
(2013/09/12)
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- Stereoselective synthesis of spirocyclic oxindoles based on a one-pot Ullmann coupling/Claisen rearrangement and its application to the synthesis of a hexahydropyrrolo[2,3-b]indole alkaloid
-
An efficient and convenient approach to the synthesis of spirocyclic oxindoles from iodoindoles has been developed. The most striking feature of this approach is that the sequential intramolecular Ullmann coupling and Claisen rearrangement proceeds in a one-pot manner to afford 3-spiro-2-oxindoles in good yield with excellent diastereoselectivity. Application of this one-pot reaction to chiral non-racemic tertiary alcohol substrates resulted in complete chirality transfer to the spirocyclic quaternary carbon. Using this method, asymmetric total synthesis of (-)-debromoflustramine B was accomplished.
- Miyamoto, Hiroshi,Hirano, Tomohiro,Okawa, Yoichiro,Nakazaki, Atsuo,Kobayashi, Susumu
-
supporting information
p. 9481 - 9493
(2013/10/08)
-
- New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity
-
A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF3, CO2Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.
- Soto, Sara,Vaz, Esther,Dell'Aversana, Carmela,Alvarez, Rosana,Altucci, Lucia,De Lera, Angel R.
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supporting information; experimental part
p. 2101 - 2112
(2012/04/23)
-
- Microwave-assisted synthesis of 3,1-benzoxazin-2-ones from 3-hydroxyoxindoles
-
A general protocol for the synthesis of 3,1-benzoxazin-2-ones 18 from 3-hydroxyoxindoles 16 in a two steps sequence through phenylsuccinates or phenylpropionates 17 is described. Best reaction conditions for ring opening of 16 to succinates or propionates 17 were achieved using alcohol/silica gel, while cyclization of 17 to benzoxazinones 18 was easily done with HCl/alcohol. It was also found that 17 and 18 can be transesterified using HCl/alcohol. Most transformations were carried out by traditional heating and by microwave (MW) irradiation to accelerate reaction rates.
- Suarez-Castillo, Oscar R.,Bautista-Hernandez, Claudia I.,Sanchez-Zavala, Maricruz,Melendez-Rodriguez, Myriam,Sierra-Zenteno, Araceli,Morales-Rios, Martha S.,Joseph-Nathan, Pedro
-
p. 2147 - 2171,25
(2020/08/31)
-
- Synthesis of Phidianidine B, a highly cytotoxic 1,2,4-oxadiazole marine metabolite
-
Phidianidine B (1), a natural 1,2,4-oxadiazole linking both an indole system and an aminoalkyl guanidine group that has been recently reported from a marine mollusk, has been synthesized in seven steps (14% total yield). The synthetic procedure, which is based on the coupling of 3-indolacetic acid methyl ester and the amino-alkyl hydroxy guanidine intermediate 2, opportunely prepared, is of general application and allows the synthesis of analogues with either different alkyl chain length or substitution on the indole ring. ARKAT-USA, Inc.
- Manzo, Emiliano,Pagano, Dario,Carbone, Marianna,Ciavatta, M. Letizia,Gavagnin, Margherita
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p. 220 - 228
(2013/02/23)
-
- Synthesis and biological evaluation of benzothiazole incorporated 1-phenylsulfonylindole-3-acetamide derivatives
-
Indole-3-acetic acid was esterified to give methyl ester (2), which was treated with substituted aromatic sulphonyl chloride in alkaline media to give 2-[1-(phenyl sufonyl-1H-indole-3-yl]methyl acetate (3). Further the compound 3 was converted to acid (4). Finally compound 4 was coupled with 6-substituted benzothiazole-2-amines by means of EDC to give acetamide derivatives (5a-i). The structures of the newly synthesized compounds have been established by analytical and spectral methods. These compounds have also been screened for analgesic activity.
- Sharma, Prince P.,Roy, Ram K.,Anurag,Verma, Krishan
-
experimental part
p. 2878 - 2880
(2012/07/28)
-
- CRTH2 antagonist MK-7246: A synthetic evolution from discovery through development
-
In this paper, we report the development of different synthetic routes to MK-7246 (1) designed by the Process Chemistry group. The syntheses were initially designed as an enabling tool for Medicinal Chemistry colleagues in order to rapidly explore structure-activity relationships (SAR) and to procure the first milligrams of diverse target molecules for in vitro evaluation. The initial aziridine opening/cyclodehydration strategy was also directly amenable to the first GMP deliveries of MK-7246 (1), streamlining the transition from milligram to kilogram-scale production needed to support early preclinical and clinical evaluation of this compound. Subsequently a more scalable and cost-effective manufacturing route to MK-7246 (1) was engineered. Highlights of the manufacturing route include an Ir-catalyzed intramolecular N-H insertion of sulfoxonium ylide 41 and conversion of ketone 32 to amine 31 in a single step with excellent enantioselectivity through a transaminase process. Reactions such as these illustrate the enabling impact and efficiency gains that innovative developments in chemo- and biocatalysis can have on the synthesis of pharmaceutically relevant target molecules.
- Molinaro, Carmela,Bulger, Paul G.,Lee, Ernest E.,Kosjek, Birgit,Lau, Stephen,Gauvreau, Danny,Howard, Melissa E.,Wallace, Debra J.,O'Shea, Paul D.
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supporting information; experimental part
p. 2299 - 2309
(2012/05/20)
-
- An organocatalytic cascade strategy for the enantioselective construction of spirocyclopentane bioxindoles containing three contiguous stereocenters and two spiro quaternary centers
-
A rapid and efficient organocatalytic cascade sequence for the direct construction of spirocyclopentane bioxindoles has been carried out by using a chiral squaramide catalyst in the presence of a base. This process constitutes a powerful approach to the preparation of biologically important bispirooxindoles in high enantioselectivities (see scheme). Copyright
- Sun, Wangsheng,Zhu, Gongming,Wu, Chongyang,Hong, Liang,Wang, Rui
-
supporting information; experimental part
p. 6737 - 6741
(2012/07/28)
-
- Synthesis and identification of novel indolo[2,3-a]pyrimido[5,4-c] carbazoles as a new class of anti-cancer agents
-
A range of 5,6-bisindole and 5-indole-6-(7-azaindole)pyrimidinones were synthesised via a β-keto ester intermediate and a screen of cyclisation conditions undertaken. The optimised route to this new class of indolocarbazoles and azaindolocarbazoles involved photocyclisation, with typical yields of 50-60%. These derivatives were screened for anti-cancer activity via topo II inhibition and the NCI-60 cell line assay, with the screening indicating a lack of topo II inhibition, but significant in vitro growth inhibition within this new chemical class, in the low micromolar range against renal cancer, melanoma and colon cancer cell lines.
- Pierce, Larry T.,Cahill, Michael M.,Winfield, Hannah J.,McCarthy, Florence O.
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p. 292 - 300
(2013/01/15)
-
- Gold-catalyzed regioselective hydration of propargyl acetates assisted by a neighboring carbonyl group: Access to α-acyloxy methyl ketones and synthesis of (±)-actinopolymorphol B
-
A general atom-economical approach for the synthesis of α-acyloxy methyl ketone is demonstrated through regioselective hydration of a wide range of propargyl acetates. Readily available catalyst comprising of 1% Ph 3PAuCl and 1% AgSbF6 in dioxane-H2O efficiently hydrolyzes the terminal alkynes of the propargyl acetate in the absence of acid promoters at ambient temperature within a short time. Effective regioselective hydration is facilitated by the neighboring carbonyl group as demonstrated through 18O-labeling study. Compatibility of functional moieties and tolerance to various acid-labile protecting groups are observed. The catalytic condition is also suitable to perform hydration of TMS-substituted propargyl acetates, even though it requires prolonged reaction time for completion. Stereointegrity of the propargylic acetate is preserved during the hydration. The robustness of the system is successfully demonstrated through gram scale preparation of the product in nearly quantitative yield. The common α-acyloxy methyl ketone is transformed to 1,2-diol and 1,2-amino alcohol derivatives. Synthesis of actinopolymorphol B is achieved for the first time involving hydration of the propargyl acetate as the key step.
- Ghosh, Nayan,Nayak, Sanatan,Sahoo, Akhila K.
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supporting information; experimental part
p. 500 - 511
(2011/04/17)
-
- Microwave-assisted synthesis of 5-substituted 2-aminothiophenes starting from arylacetaldehydes
-
An easy three-step pathway for the synthesis of arylacet-aldehydes from the corresponding carboxylic acids in very high yields is described. Their use as precursors of 5-substituted-2-aminothiophenes is illustrated via a microwave-assisted Gewald reaction. This method allows obtaining the expected compounds in a shorter time and with better yields and purities than the classical procedures. Georg Thieme Verlag Stuttgart - New York.
- Revelant, Germain,Dunand, Sandrine,Hesse, Stephanie,Kirsch, Gilbert
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experimental part
p. 2935 - 2940
(2011/11/01)
-