- Bioactive derivatives of isopropylstilbene from mutasynthesis and chemical synthesis
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Isopropylstilbene is a natural product from Photorhabdus lumi-nescens TT01, with multiple biological activities. A mutant deficient in the production of both anthraquinones and cinnamic acid was constructed, thus giving a clean background according to UV detection. This anthraquinone and stilbene deficient (ASD) mutant was used in mutasynthesis experiments to obtain new stilbene derivatives, which were detected by GC-MS. The structures of the new derivatives were confirmed by detailed MS analysis and then chemically synthesised; all of the natural and synthetic compounds were tested against protozoa that cause tropical diseases. Two compounds obtained by mutasynthesis showed the highest activity against Trypanosoma cruzi, the causative agent of Chagas disease, and Leishmania donovani, which causes leishmaniasis.
- Kronenwerth, Max,Brachmann, Alexander O.,Kaiser, Marcel,Bode, Helge B.
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- Ligand-controlled cobalt-catalyzed remote hydroboration and alkene isomerization of allylic siloxanes
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The Co-catalyzed remote hydroboration and alkene isomerization of allylic siloxanes were realized by a ligand-controlled strategy. The remote hydroboration with dcype provided borylethers, while xantphos favored the formation of silyl enol ethers.
- Huang, Jiaxin,Li, Jie,Yang, Wen,Zhang, Kezhuo,Zhao, Pei,Zhao, Wanxiang
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p. 302 - 305
(2022/01/03)
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- Synthesis of rac-ɑ-aryl propionaldehydes via branched-selective hydroformylation of terminal arylalkenes using water-soluble Rh-PNP catalyst
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This work detailed the preparation of a class of water-soluble PNP ligands that differed by the nature of the substitute on phenyl ring of ligands. These ligands were incorporated into water-soluble rhodium-PNP complex catalysts that were used to regioselective hydroformylation of a series of terminal arylalkenes, providing efficient access to rac-α-aryl propionaldehydes in good to excellent yield (up to 97%) and branched-regioselectivity (up to 40:1 b/l ratio). Furthermore, gram-scale and diverse synthetic transformation demonstrated synthetic application of this methodology for non-steroidal antiinflammatory drugs.
- Chen, Fen-Er,Gao, Peng,Ke, Miaolin,Liang, Guanfeng,Ru, Tong
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- Insight into decomposition of formic acid to syngas required for Rh-catalyzed hydroformylation of olefins
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Formic acid (FA) is one kind of important bulk chemicals, which is recognized as a sustainable and eco-friendly energy carrier to transport H2 via dehydrogenation or CO via decarbonylation. Expectantly, FA upon decomposition into H2 and CO could be used as the syngas alternative for hydroformylation. In this paper, the behaviors of FA to release H2 as well as CO following the distinct pathways were carefully investigated for the first time, and then established a new hydroformylation protocol free of syngas. It was found that the atmospheric hydroformylation of olefins with formic acid (FA) as syngas alternative was smoothly fulfilled over Xantphos (L1) modified Rh-catalyst under mild conditions (80 °C, Rh concentration 1 mol %, 14 h), resulting in >90% conversion of the olefins along with the high selectivity to the target aldehydes (>93%). By using FA as syngas source, the side-reaction of olefin-hydrogenation was greatly depressed. The in situ FT-IR and the high-pressure 1H NMR spectroscopic analyses were applied to reveal how FA behaves dually as CO surrogate and hydrogen source over L1-Rh(acac)(CO)2 catalytic system, based on which the deeply insight into the catalytic mechanism of hydroformylation of olefins with FA as syngas alternative was offered.
- Liu, Lei,Chen, Xiao-Chao,Yang, Shu-Qing,Yao, Yin-Qing,Lu, Yong,Liu, Ye
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p. 406 - 415
(2020/12/07)
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- Access to Trisubstituted Fluoroalkenes by Ruthenium-Catalyzed Cross-Metathesis
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Although the olefin metathesis reaction is a well-known and powerful strategy to get alkenes, this reaction remained highly challenging with fluororalkenes, especially the Cross-Metathesis (CM) process. Our thought was to find an easy accessible, convenient, reactive and post-functionalizable source of fluoroalkene, that we found as the methyl 2-fluoroacrylate. We reported herein the efficient ruthenium-catalyzed CM reaction of various terminal and internal alkenes with methyl 2-fluoroacrylate giving access, for the first time, to trisubstituted fluoroalkenes stereoselectively. Unprecedent TON for CM involving fluoroalkene, up to 175, have been obtained and the reaction proved to be tolerant and effective with a large range of olefin partners giving fair to high yields in metathesis products. (Figure presented.).
- Nouaille, Augustin,Pannecoucke, Xavier,Poisson, Thomas,Couve-Bonnaire, Samuel
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p. 2140 - 2147
(2021/03/06)
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- Carbene-Catalyzed α-Carbon Amination of Chloroaldehydes for Enantioselective Access to Dihydroquinoxaline Derivatives
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An NHC-catalyzed α-carbon amination of chloroaldehydes was developed. Cyclohexadiene-1,2-diimines are used as amination reagents and four-atom synthons. Our reaction affords optically enriched dihydroquinoxalines that are core structures in natural products and synthetic bioactive molecules.
- Huang, Ruoyan,Chen, Xingkuan,Mou, Chengli,Luo, Guoyong,Li, Yongjia,Li, Xiangyang,Xue, Wei,Jin, Zhichao,Chi, Yonggui Robin
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p. 4340 - 4344
(2019/06/14)
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- Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y2 Receptor Based on AR-C118925
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The human P2Y2 receptor (hP2Y2R) is a G-protein-coupled receptor that shows promise as a therapeutic target for many important conditions, including for antimetastatic cancer and more recently for idiopathic pulmonary fibrosis. As such, there is a need for new hP2Y2R antagonists and molecular probes to study this receptor. Herein, we report the development of a new series of non-nucleotide hP2Y2R antagonists, based on the known, non-nucleotide hP2Y2R antagonist AR-C118925 (1), leading to the discovery of a series of fluorescent ligands containing different linkers and fluorophores. One of these conjugates, 98, displayed micromolar affinity for hP2Y2R (pKd = 6.32 ± 0.10, n = 17) in a bioluminescence-energy-transfer (BRET) assay. Confocal microscopy with this ligand revealed displaceable membrane labeling of astrocytoma cells expressing untagged hP2Y2R. These properties make 98 one of the first tools for studying hP2Y2R distribution and organization.
- Conroy, Sean,Kindon, Nicholas D.,Glenn, Jacqueline,Stoddart, Leigh A.,Lewis, Richard J.,Hill, Stephen J.,Kellam, Barrie,Stocks, Michael J.
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p. 3089 - 3113
(2018/04/23)
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- Synthesis and bioactivities of novel piperazine-containing 1,5-Diphenyl-2-penten-1-one analogues from natural product lead
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A series of novel 1,5-Diphenyl-2-penten-1-one analogues (7a–h, 8a–h) with piperazine moiety have been designed and synthesized on the basis of natural product 1,5-Diphenyl-2-penten-1-one (I). All the synthesized compounds were evaluated in vitro for anti-plant pathogenic fungi activities and insecticidal activities. The results indicated that most of these analogues exhibited moderate antifungal activities and moderate to good insecticidal activities. Amongst them, the most potent 7c, 7e and 7h keep a mortality of 100% against larva of mosquito at the concentration of 1?mg/L. Initial structure–activity relationship (SAR) analysis showed that, a methyl group can influence the biological activities of these compounds significantly, the compounds with N′-unsubstituted piperazine showed much better antifungal activities and larvicidal activity against mosquito than the compounds with N′-methylated piperazine. In addition, the larvicidal activity against mosquito had sharply decline when the substituent on benzene ring was changed from 4-position to 2 or 3-position.
- Xu, Gaofei,Yang, Xinling,Jiang, Biaobiao,Lei, Peng,Liu, Xili,Wang, Qingmin,Zhang, Xuebo,Ling, Yun
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p. 1849 - 1853
(2016/07/27)
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- New class of bioluminogenic probe based on bioluminescent enzyme-induced electron transfer: BioLeT
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Bioluminescence imaging (BLI) has advantages for investigating biological phenomena in deep tissues of living animals, but few design strategies are available for functional bioluminescent substrates. We propose a new design strategy (designated as bioluminescent enzyme-induced electron transfer: BioLeT) for luciferin-based bioluminescence probes. Luminescence measurements of a series of aminoluciferin derivatives confirmed that bioluminescence can be controlled by means of BioLeT. Based on this concept, we developed bioluminescence probes for nitric oxide that enabled quantitative and sensitive detection even in vivo. Our design strategy should be applicable to develop a wide range of practically useful bioluminogenic probes.
- Takakura, Hideo,Kojima, Ryosuke,Kamiya, Mako,Kobayashi, Eiji,Komatsu, Toru,Ueno, Tasuku,Terai, Takuya,Hanaoka, Kenjiro,Nagano, Tetsuo,Urano, Yasuteru
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p. 4010 - 4013
(2015/04/14)
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- Lewis Acid Catalyzed Cyclizations of Epoxidized Baylis-Hillman Products: A Straightforward Synthesis of Octahydrobenzo[e]azulenes
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Tricyclic keto-diols have been synthesized from 2-cyclopenten-1-one in a three-step annulation procedure. The importance of aryl ring electronics and steric contributions and the choice of Lewis acid were investigated for the final cyclization step. An unexpected cyclization product was identified, suggesting multiple mechanisms for the cyclization process. The Lewis acid catalyzed Baylis-Hillman reaction has been used for the stereoselective synthesis of fused 5-7-6 ring systems. The isolation of an unexpected regioisomer from the reaction with (methylphenyl)propionaldehyde provides insights into the probable mechanisms operative in the reaction.
- Konopacki, Donald B.,Shortsleeves, Kelley C.,Turnbull, Mark M.,Wikaira, Jan L.,Hobson, Adrian D.
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p. 5453 - 5463
(2015/08/24)
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- Rhodium/phospholane-phosphite catalysts give unusually high regioselectivity in the enantioselective hydroformylation of vinyl arenes
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Using the phospholane-phosphite ligand, BOBPHOS, almost perfect regioselectivities and high enantioselectivities (up to 92% ee) are observed in Rh catalysed enantioselective hydroformylation of vinyl arenes. This can be achieved under solvent-free conditions. The Royal Society of Chemistry.
- Noonan, Gary M.,Cobley, Christopher J.,Mahoney, Thomas,Clarke, Matthew L.
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supporting information
p. 1475 - 1477
(2014/02/14)
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- Ligand-metal cooperating PC(sp3)P pincer complexes as catalysts in olefin hydroformylation
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Ligand-metal cooperation: A new ligand-metal cooperating catalyst for the hydroformylation of olefins is described (see scheme). The mechanism of the H2 activation and C-H bond formation of the catalyst involves an intramolecular cooperation between the structurally remote functionality and the metal center and proceeds without change of the oxidation state of the metal.
- Musa, Sanaa,Filippov, Oleg A.,Belkova, Natalia V.,Shubina, Elena S.,Silantyev, Gleb A.,Ackermann, Lutz,Gelman, Dmitri
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supporting information
p. 16906 - 16909
(2014/01/06)
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- Novel and potent inhibitors of stearoyl-CoA desaturase-1. Part I: Discovery of 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide
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A series of structurally novel stearoyl-CoA desaturase-1 (SCD-1) inhibitors has been identified by optimizing a hit from our corporate library. Preliminary structure-activity relationship (SAR) studies led to the discovery of the highly potent and orally bioavailable thiazole-based SCD-1 inhibitor, 3-(2-hydroxyethoxy)-4-methoxy-N-[5-(3-trifluoromethylbenzyl)thiazol-2-yl]benzamide (23a).
- Uto, Yoshikazu,Ogata, Tsuneaki,Harada, Jun,Kiyotsuka, Yohei,Ueno, Yuko,Miyazawa, Yuriko,Kurata, Hitoshi,Deguchi, Tsuneo,Watanabe, Nobuaki,Takagi, Toshiyuki,Wakimoto, Satoko,Okuyama, Ryo,Abe, Manabu,Kurikawa, Nobuya,Kawamura, Sayako,Yamato, Michiko,Osumi, Jun
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scheme or table
p. 4151 - 4158
(2010/04/29)
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- 5,6,7,8-TETRAHYDRO-IMIDAZO[1,5-A]PYRAZINE DERIVATIVES
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The invention relates to 5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine derivatives of formula (I),wherein X represents CH2 or O; R1 represents a phenyl group, which group is independently mono-, di-, or tri-substituted wherein the substituents are independently selected from the group consisting of (C1-4)alkyl, (C1-4)alkoxy, halogen, cyano, trifluoromethoxy and trifluoromethyl; R2 represents (C1-4)alkyl, (C1-4)alkoxy, (C2-4)alkenyl, halogen, cyano, hydroxymethyl, trifluoromethyl, C(O)NR5R6 or cyclopropyl; R3 represents (C1-4)alkyl, (C1-4)alkoxy-methyl or halogen; R4 represents (C1-4)alkyl; R5 represents hydrogen or (C1-4)alkyl; and R6 represents hydrogen or (C1-4)alkyl. The invention also relates to pharmaceutically acceptable salts of such compounds; and to the use of such compounds as medicaments; especially as orexin receptor antagonists.
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Page/Page column 54
(2008/12/06)
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- Highly selective hydroformylation of vinylarenes to branched aldehydes by [Rh(cod)Cl]2 entrapped in ionic liquid modified silica sol-gel
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A co-entrapped mixture of [Rh(cod)Cl]2 and Na[Ph 2P-3-(C6H4SO3)] within a silica sol-gel matrix modified with ca. 5% of 1-butyl-3-[3-(trimethoxysilyl)propyl] imidazolium chloride catalyzes, in n-heptane, the hydroformylation of a variety of vinylarenes. At 50°C and under 6.9 bar each of H2 and CO the reaction is high-yielding and highly selective. Non-hindered substrates give >95 % of branched aldehydes and only 5% of the linear isomers. The ceramic catalyst is leach-proof and recyclable. It does not lose its high catalytic activity and selectivity for at least four runs. The selectivity depends on the pressure of the gases, the temperature and the solvent. The electronic nature has no influence on the selectivity, but the latter is diminished by steric effects. Upon omission of the sol-gel component, the catalyst deteriorates and practically loses its activity after the first half-life of the reaction. In the absence of the ionic liquid, the catalyst undergoes substantial leaching. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Hamza, Khalil,Blum, Jochanan
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p. 4706 - 4710
(2008/03/13)
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- Structure-activity relationships for the linker in a series of pyridinyl-alkynes that are antagonists of the metabotropic glutamate receptor 5 (mGluR5)
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Studies of structure-activity relationships for the linker in a new series of metabotropic glutamate receptor 5 antagonists are presented together with in vitro and in vivo pharmacokinetic data.
- Bach, Peter,Nilsson, Karolina,Svensson, Tor,Bauer, Udo,Hammerland, Lance G.,Peterson, Alecia,Wallberg, Andreas,Oesterlund, Krister,Karis, David,Boije, Maria,Wensbo, David
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p. 4788 - 4791
(2007/10/03)
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- ALKYNES I
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The present invention is directed to novel compounds of formula (I), to a process for their preparation, their use in therapy and pharmaceutical compositions comprising the novel compounds. The novel compounds are useful in therapy, and in particular for the treatment of gastroesophageal reflux disease (GERD).
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Page/Page column 12
(2010/02/11)
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- Methods of treatment using an EP2 selective receptor agonist
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The present invention relates to methods of treating pulmonary hypertension, facilitating joint fusion, facilitating tendon and ligament repair, reducing the occurrence of secondary fracture, treating avascular necrosis, facilitating cartilage repair, facilitating bone healing after limb transplantation, facilitating liver regeneration, facilitating wound healing, reducing the occurrence of gastric ulceration, treating hypertension, facilitating the growth of tooth enamel or finger or toe nails, treating glaucoma, treating ocular hypertension, and repairing damage caused by metastatic bone disease using an EP2 selective receptor agonist.
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Page/Page column 44
(2010/02/13)
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- One-pot synthesis of metalated pyridines from two acetylenes, a nitrile, and a titanium(II) alkoxide
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Four-component coupling process involving two acetylenes, a nitrile, and a divalent titanium alkoxide reagent, Ti(O-i-Pr)4/2i-PrMgCl, directly yielded titanated pyridines in a highly selective manner. The reaction can be classified into four categories: (i) a combination of an internal acetylene, a terminal acetylene, sulfonylnitrile, and the titanium reagent to yield α-titanated pyridines, (ii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield alternative α-titanated pyridines, (iii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield titanated aminopyridines, and (iv) a combination of an acetylenic amide, a terminal acetylene, a nitrile, and the titanium reagent to yield pyridineamides with their side chain titanated. Some of these reactions enabled virtually completely regioselective coupling of two different, unsymmetrical acetylenes and a nitrile to form a single pyridine. Synthetic applications of these reactions have been illustrated in the preparation of optically active pyridines and medicinally useful compounds.
- Tanaka, Ryoichi,Yuza, Akio,Watai, Yuko,Suzuki, Daisuke,Takayama, Yuuki,Sato, Fumie,Urabe, Hirokazu
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p. 7774 - 7780
(2007/10/03)
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- Method for treating glaucoma
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Methods of using prostaglandin agonists for the reduction of intraocular pressure, and accordingly glaucoma.
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- Prostaglandin agonists and their use to treat bone disorders
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This invention relates to prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.
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- Cyclic regimens using cyclocarbamate and cyclic amide derivatives
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This invention relates to cyclic combination therapies and regimens utilizing, in combination with progestins, substituted indoline derivative compounds which are antagonists of the progesterone receptor having the general structure: where A and B are ind
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- Prevention of loss and restoration of bone mass by certain prostaglandin agonists
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Prostaglandin agonists of formula (I), in which, for example, A is a sulphonyl or acyl group, B is N or CH, M contains a ring and K and Q are linking groups, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits useful for the treatment of bone disorders including osteoporosis. STR1
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- Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitors: 2-oxetanones with a side chain mimicking the folded structure of 1233A.
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To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-1-naphthyl)ethyl]-2-oxe tanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.
- Hashizume,Ito,Yamada,Nagashima,Kanao,Tomoda,Sunazuka,Kumagai,Omura
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p. 512 - 520
(2007/10/02)
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