41 research outputs found

    Canvass: a crowd-sourced, natural-product screening library for exploring biological space

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    NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

    An Enantioselective Total Synthesis of (−)-Isoschizogamine

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    A concise enantioselective total synthesis of (¢)- isoschizogamine, a complex bridged polycyclic monoterpene indole alkaloid, was accomplished. N-Alkylation of an enantio- enriched imine with an alkyl iodide afforded an iminium salt, which, upon heating by microwave irradiation in the presence of pivalic acid, was converted into the hexacyclic structure of natural product by a complex but ordered domino sequence. The one-pot process leading to the formation of one C¢C bond and three C¢N bonds created three rings and three contiguous stereogenic centers with complete control of both the relative and absolute stereochemistry

    Enantioselective Total Syntheses of Leuconolam–Leuconoxine–Mersicarpine Group Monoterpene Indole Alkaloids

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    A unified strategy allowing enantioselective total syntheses of (−)-mersicarpine, (−)-scholarisine G, (+)-melodinine E, (−)-leuconoxine, and (−)-leuconolam from a common cyclohexenone derivative was reported. The Suzuki−Miyaura reaction was used to couple two simple fragments incorporating the key elements for total synthesis, and unprecedented oxidation/reduction/cyclization processes were developed that converted the substituted cyclohexenone to either a mersicarpine or leuconoxine skeleton. In a reverse biomimetic synthesis fashion, (+)-melodinine E was converted to (−)-leuconolam under acidic conditions

    Palladium-Catalyzed Decarboxylative Vinylation of Potassium Nitrophenyl Acetate: Application to the Total Synthesis of (±)-Goniomitine

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    Merge and divert. (±)-goniomitine was synthesized featuring two key steps: a) fragment coupling to functionalized cyclopentene by a novel palladium-catalyzed decarboxylative vinylation reaction and b) an unprecedented one-pot integrated oxidation/reduction/cyclization (IORC) process to convert the substituted cyclopentene to tetracyclic skeleton of goniomitine. In this IORC process, oxidative scission of one double bond, reduction of azido and nitro groups, formation of three C-N bonds with the concurrent formation of three rings took place with high degree of chemo-, regio- and diastereo-selectivities

    Unified Strategy to Monoterpene Indole Alkaloids: Total Syntheses of (±)-Goniomitine, (±)-1,2-Dehydroaspidospermidine, (±)-Aspidospermidine, (±)-Vincadifformine, and (±)-Kopsihainanine A

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    Total syntheses of (±)-goniomitine, (±)-1,2-dehydroaspidospermidine, (±)-aspidospermidine, (±)-vincadifformine, and (±)-kopsihainanine A were achieved featuring two common key steps: (1) a palladium-catalyzed decarboxylative vinylation that provides quick access to cyclopentene intermediates containing all of the carbons present in the natural products and (2) an integrated oxidation/reduction/cyclization (iORC) sequence for skeletal reorganization that converts the cyclopentenes to the pentacyclic structures of the natural products. By incorporation of a geometric constraint to iORC substrates, both the chemoselectivity (C7 vs N1 cyclization) and the stereoselectivity (trans- vs cis-fused ring system) of the cyclization process can be controlled

    Discovery and Characterization of 1-Aminocyclopropane-1-carboxylic Acid Synthase of Bacterial Origin

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    Enantioselective Total Syntheses of (−)-Rhazinilam, (−)-Leucomidine B, and (+)-Leuconodine F

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    A divergent total synthesis of three structurally distinct natural products from imine 9 was accomplished through an approach featuring: 1) a Pd-catalyzed decarboxylative cross-coupling, and 2) heteroannulation of 9 with bromoacetaldehyde and oxalyl chloride to give tetrahydroindolizine 6 and dioxopyrrole 7, respectively. The former was converted into (-)-rhazinilam, while the latter was converted into (-)-leucomidine B and (+)-leuconodine F. A substrate directed highly diastereoselective reduction of a sterically unbiased double bond by using a homogeneous palladium catalyst was developed. A self-induced diastereomeric anisochronism (SIDA) phenomenon was observed for leucomidine B

    Fan Fault Diagnosis Based on Wavelet Packet and Sample Entropy

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    To accurately diagnose the mechanical failure of the fan, two diagnostic methods based on the wavelet packet energy feature and sample entropy feature are proposed. Vibration signals acquisition of 13 kinds of running states are achieved on the 4-73 No.8D centrifugal fan test bench. The wavelet packet energy feature vector of each vibration signal is rapidly extracted through the wavelet packet denoising, decomposition and reconstruction. The vibration signal wavelet packet energy feature vector of the five measuring points in the same instantaneous running state are fused into the fan fault feature vector. Finally, the fault diagnosis of the fan is achieved by using improved SVM (Support Vector Machine) classifier, and the accuracy rate is 94.6%. A new fan fault feature vector is put forward, which is the integration of the vibration signal sample entropy of the five measuring points in the same instantaneous running state, and then the fault diagnosis of the fan is achieved by using improved BP (Back Propagation) neural network, and the accuracy rate is 99.23%. The diagnostic results show that these two methods are able to effectively diagnose the category, severity and site of the fan mechanical failures, and suitable for online diagnosis. DOI: http://dx.doi.org/10.11591/telkomnika.v11i6.272

    Aqueous Titanium Trichloride Promoted Reductive Cyclization of o-Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine

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    Treatment of o-nitrostyrenes with aqueous TiCl3 solution at room temperature afforded indoles via a formal reductive C(sp2)-H amination process. A range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxyl and amino groups were tolerated. From β, β-disubstituted o-nitrostyrenes, 2,3-disubstituted indoles were formed via a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterized the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine

    Enantioselective Total Syntheses of Leuconolam–Leuconoxine–Mersicarpine Group Monoterpene Indole Alkaloids

    No full text
    A unified strategy allowing enantioselective total syntheses of (−)-mersicarpine, (−)-scholarisine G, (+)-melodinine E, (−)-leuconoxine, and (−)-leuconolam from a common cyclohexenone derivative was reported. The Suzuki–Miyaura reaction was used to couple two simple fragments incorporating the key elements for total synthesis, and unprecedented oxidation/reduction/cyclization processes were developed that converted the substituted cyclohexenone to either a mersicarpine or leuconoxine skeleton. In a reverse biomimetic synthesis fashion, (+)-melodinine E was converted to (−)-leuconolam under acidic conditions
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