DOCSLIB.ORG

Chiral Thioureas—Preparation and Significance in Asymmetric

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chiral Thioureas—Preparation and Significance in Asymmetric molecules Review Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry Franz Steppeler 1 , Dominika Iwan 1, El˙zbietaWojaczy ´nska 1,* and Jacek Wojaczy ´nski 2 1 Faculty of Chemistry, Wrocław University of Science and Technology, Wybrze˙zeWyspia´nskiego 27, 50 370 Wrocław, Poland; [email protected] (F.S.); [email protected] (D.I.) 2 Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie St., 50 383 Wrocław, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-71-320-2410 Academic Editors: Zbigniew Czarnocki and Joanna Szawkało Received: 29 December 2019; Accepted: 16 January 2020; Published: 18 January 2020 Abstract: For almost 20 years, thioureas have been experiencing a renaissance of interest with the emerged development of asymmetric organocatalysts. Due to their relatively high acidity and strong hydrogen bond donor capability, they differ significantly from ureas and offer, appropriately modified, great potential as organocatalysts, chelators, drug candidates, etc. The review focuses on the family of chiral thioureas, presenting an overview of the current state of knowledge on their synthesis and selected applications in stereoselective synthesis and drug development. Keywords: asymmetric synthesis; chirality; isothiocyanates; organocatalysis; stereoselectivity; thioureas 1. Introduction The replacement of the electronegative oxygen atom of urea by sulfur (with electronegativity comparable to carbon) results in a significant change of properties. Thioureas (thiocarbamides) exhibit higher acidity and are stronger hydrogen bond donors [1–3]. This ability to participate in hydrogen bonding, which can be further modified by the appropriate substitution of nitrogen atoms, is essential for numerous applications of this class of organic compounds, mainly in organocatalysis and molecular recognition. Thioureas are also widely applied in agriculture and medicine [4–7], and as corrosion inhibitors [8–11]. For almost 20 years they have been used as catalysts in organic synthesis, especially in stereoselective reactions [12–14]. They also serve as valuable starting materials for the synthesis of heterocycles [15–17], and are used as ligands in coordination chemistry (particularly when additional donors are present in their molecules) [18–22], as well as in the field of anion binding and recognition [2,23]. Structurally thioureas can be classified depending on the number of substituents of nitrogen atom (Figure1)[ 6,7]. Not surprisingly, derivatives with one and two organic groups (either 1,1 or 1,3-disubstituted) are most common, though trisubstituted (with limited, but still preserved possibility to act as hydrogen bond donors) and fully substituted (mainly cyclic) thioureas are also prepared and used for various purposes. The first thiocarbamides were prepared ca. 150 years ago [24,25], and their chiral derivatives have been long known [26,27], but a great interest in the latter has arisen with the development of enantioselective organocatalysis. Molecules 2020, 25, 401; doi:10.3390/molecules25020401 www.mdpi.com/journal/molecules Molecules 2020, 25, x 2 of 57 Molecules 2020, 25, 401x 22 of of 57 56 (a) (b) (c) (d) (e) (a) (b) (c) (d) (e) Figure 1. TypesTypes of of thioureas; thioureas; (a) ( amonosubstituted;) monosubstituted; (b) (b1,1-disubstituted;) 1,1-disubstituted; (c) 1,3-disubstituted; (c) 1,3-disubstituted; (d) (Figuretrisubstituted;d) trisubstituted; 1. Types (e )of tetrasubstituted. (e )thioureas; tetrasubstituted. (a) monosubstituted; (b) 1,1-disubstituted; (c) 1,3-disubstituted; (d) trisubstituted; (e) tetrasubstituted. 2. Synthesis of Chiral Thioureas 2. SynthesisSince the of thioureaChiral Thioureas skeleton is notnot intrinsicallyintrinsically chiral, the existence of enantiomersenantiomers typically originatesSince fromthe thiourea its substituents.substituents. skeleton isExamples Examples not intrinsicall of of va variousriousy chiral, groups the bearingexistence stereogenic of enantiomers centers typically will be presentedoriginates ininfrom thethe subsequentitssubsequent substituents. section. section. Examples Desymmetrisation Desymmetrisation of various resulting groupsresulting bearing from from less less stereogenic common common axial centersaxial (biphenyl (biphenyl will be or binaphthylpresentedor binaphthyl in derivatives) the derivatives) subsequent [28 [28–30]– 30section.] or or planar planarDesymmetrisation chirality chirality [ 31[31–33]–33 resulting] is is also also from worth worth less mentioning.mentioning. common axial Consequently, (biphenyl theor binaphthyl methods of derivatives) synthesis of [28–30] chiral or thioureas planar chiral are essentiallyesseityntially [31–33] the is alsosame worth as for mentioning. their achiral Consequently, counterparts, but,the methods typically, of thethe synthesis reactants reactants of fromchiral from a thioureas achiral chiral pool pool are are esse are usedntially used in inenantiomerically the enantiomerically same as for their pure pure achiral form. form. However,counterparts, However, the thebut,preparation preparation typically, of the the of reactants thedesired desired productfrom product a chiral as asracemic racemicpool are mixture mixtureused in followed followedenantiomerically by by separation separation pure ofform. of enantiomers enantiomers However, was the reportedpreparation in selectedof the desired cases, e.g.,product bis-thiourea as racemic derivativesderiva mixturetives offollowed Tröger’s by base separation werewere obtained of enantiomers as racemates was andreported resolved in selected on a chiralchiral cases, stationarystationary e.g., bis-thiourea phasephase [[34].34 deriva]. Similarly,tives of enantiomersenantiomers Tröger’s base ofof we norbornanenorbornanere obtained thiocarbamidethiocarbamide as racemates formedand resolved as 1:1 on mixture a chiral in astationary two-step phase protocol [34]. from Similarly, norbornene enantiomers were separated of norbornane either by thiocarbamide chiral HPLC orformed by crystallizationcrystallization as 1:1 mixture of in diastereomericdiastere a two-stepomeric protocol salts ofoffrom thethe norbornene amineamine intermediatesintermediates were separated [[35].35]. Theeither advantage by chiral ofHPLC this approachor by crystallization lays in the of fact diastere that bothomeric optical salts antipodes of the amine of chiral intermediates thiourea can[35]. be The isolated advantage and used of this as organocatalystsapproach lays in or the for fact chiralchiral that recognition.recognition. both optical antipodes of chiral thiourea can be isolated and used as organocatalystsThe choice ofofor a afor particularparticular chiral recognition. method method of of preparation preparation of of the the desired desired stereoisomer stereoisomer depends depends mainly mainly on on its structureits structureThe choice (number (number of a and particular typeand oftype substituents)method of substituents) of preparation and availability and of availabilitythe ofdesired necessary stereoisomerof necessary startingmaterials. dependsstarting mainlymaterials. Certainly, on oneitsCertainly, structure should one also (number should consider andalso possible typeconsider of inconveniences substituents) possible inco (bothandnveniences availability for the (both person of for conductingnecessary the person starting the conducting synthesis materials. andthe forCertainly,synthesis the environment) and one for should the environment) connectedalso consider with connected possible the use withinco of certain nveniencesthe use reactants:of certain (both reactants:for their the limited person their stability, limitedconducting stability, toxicity, the flammability,synthesistoxicity, flammability, and orfor simply the environment) or an simply unpleasant an connected unpleasant odor. In withmost odor. the preparations, In use most of certainpreparations, reactants reactants: containingreactants their limited containing C=S bondstability, C=S are used—mainlytoxicity,bond are flammability, used—mainly isothiocyanates, or isothiocyanates, simply but an alsounpleasant dithiocarbamates, but also od or.dithiocarbamates, In most carbon preparations, disulfide, carbon reactants disulfide, thiophosgene containing thiophosgene and their C=S equivalents.bondand theirare used—mainly equivalents. Less frequently, isothiocyanates,Less inorganic frequently, sources but inorga also of sulfurdithiocarbamates,nic sources are useful of forsulfur carbon a given are disulfide, transformation—P useful thiophosgenefor a given4S10 orandtransformation—P Lawesson’s their equivalents. reagent4S10 toor Less convertLawesson’s frequently, urea intoreagent thioureainorga to nicconvert [ 36sources,37] sulfidesurea of intosulfur or elementalthiourea are useful [36,37] sulfur. for Aminessulfides a given areor thetransformation—Pelemental most usual sulfur. source Amines4S10 ofor thiourea areLawesson’s the mo nitrogenst usualreagent atoms; source tohowever, ofconvert thiourea isocyanidesurea nitrogen into thioureaatoms; and azides however, [36,37] are also isocyanidessulfides found or in variouselementaland azides protocols. sulfur. are also Amines An found alternative are in variou the mo routesst protocols. usual involves source An modification alternativeof thiourea ofroute nitrogen already involves atoms; constructed modification however, achiral isocyanides of thiourea already withandconstructed azides optically are achiral
Load more

Recommended publications
  • Last Decade of Unconventional Methodologies for the Synthesis Of
    Review molecules Last Decade of Unconventional Methodologies for theReview Synthesis of Substituted Benzofurans Last Decade of Unconventional Methodologies for the Lucia Chiummiento *, Rosarita D’Orsi, Maria Funicello and Paolo Lupattelli Synthesis of Substituted Benzofurans Department of Science, Via dell’Ateneo Lucano, 10, 85100 Potenza, Italy; [email protected] (R.D.); [email protected] (M.F.); [email protected] (P.L.) Lucia Chiummiento * , Rosarita D’Orsi, Maria Funicello and Paolo Lupattelli * Correspondence: [email protected] Department of Science, Via dell’Ateneo Lucano, 10, 85100 Potenza, Italy; [email protected] (R.D.); Academic Editor: Gianfranco Favi [email protected] (M.F.); [email protected] (P.L.) Received:* Correspondence: 22 April 2020; [email protected] Accepted: 13 May 2020; Published: 16 May 2020 Abstract:Academic This Editor: review Gianfranco describes Favi the progress of the last decade on the synthesis of substituted Received: 22 April 2020; Accepted: 13 May 2020; Published: 16 May 2020 benzofurans, which are useful scaffolds for the synthesis of numerous natural products and pharmaceuticals.Abstract: This In review particular, describes new the intramolecular progress of the and last decadeintermolecular on the synthesis C–C and/or of substituted C–O bond- formingbenzofurans, processes, which with aretransition-metal useful scaffolds catalysi for thes or synthesis metal-free of numerous are summarized. natural products(1) Introduction. and (2) Ringpharmaceuticals. generation via In particular, intramolecular new intramolecular cyclization. and (2.1) intermolecular C7a–O bond C–C formation: and/or C–O (route bond-forming a). (2.2) O– C2 bondprocesses, formation: with transition-metal (route b).
    [Show full text]
  • Enantioselective Synthesis of (-)-Vallesine: Late- Stage C17-Oxidation Via Complex Indole Boronation
    Enantioselective synthesis of (-)-vallesine: late- stage C17-oxidation via complex indole boronation The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Antropow, Alyssa H., et al., "Enantioselective synthesis of (-)-vallesine: late-stage C17-oxidation via complex indole boronation." Organic Letters 20, 12 (2018): p. 3647-50 doi 10.1021/ acs.orglett.8b01428 ©2018 Author(s) As Published 10.1021/acs.orglett.8b01428 Publisher American Chemical Society (ACS) Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/125882 Terms of Use Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Org Lett Manuscript Author . Author manuscript; Manuscript Author available in PMC 2019 June 15. Published in final edited form as: Org Lett. 2018 June 15; 20(12): 3647–3650. doi:10.1021/acs.orglett.8b01428. Enantioselective Synthesis of (−)-Vallesine: Late-stage C17- Oxidation via Complex Indole Boronation Alyssa H. Antropow, Nicholas R. Garcia, Kolby L. White, and Mohammad Movassaghi* Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Abstract The first enantioselective total synthesis of (−)-vallesine via a strategy that features a late-stage regioselective C17-oxidation, followed by a highly stereoselective transannular cyclization is reported. The versatility of this approach is highlighted by divergent synthesis of the archetypal alkaloid of this family, (+)-aspidospermidine, and an A-ring oxygenated derivative (+)- deacetylaspidospermine, the precursor to (−)-vallesine, from a common intermediate.
    [Show full text]
  • Development of Enantioselective Organocatalysis by Bifunctional Indane Amine-Thiourea Catalyst
    DEVELOPMENT OF ENANTIOSELECTIVE ORGANOCATALYSIS BY BIFUNCTIONAL INDANE AMINE-THIOUREA CATALYST REN QIAO NATIONAL UNIVERSITY OF SINGAPORE 2013 DEVELOPMENT OF ENANTIOSELECTIVE ORGANOCATALYSIS BY BIFUNCTIONAL INDANE AMINE-THIOUREA CATALYST REN QIAO (B.Sc., Sichuan Univ.) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF CHEMISTRY NATIONAL UNIVERSITY OF SINGAPORE 2013 To my parents for their endless love, support and encouragement PHD DISSERTATION 2013 REN QIAO Thesis Declaration I hereby declare that this thesis is my original work and it has been written by me in its entirety, under the supervision of A/P Wang Jian, Chemistry Deparrtment, National University of Singapore, between 08/2009 and 09/2013. I have duly acknowledged all the sources of information which have been used in the thesis. This thesis has also not been submitted for any degree in any university previously The contents of the thesis have been partly published in: 1. Qiao Ren, Jian Wang. Asian J. Org. Chem. 2013, 2, 542. 2. Qiao Ren, Jiayao Huang, Lei Wang, Wenjjun Li, Hui Liu, Xuefeng Jiang, Jian Wang. ACS Catal. 2012, 2, 2622. 3. Qiao Ren, Woon-Yew Siau, Zhiyun Du, Kun Zhang, Jian Wang. Chem. –Eur. J. 2011, 17, 7781. 4. Qiao Ren, Yaojun Gao, Jian Waanng. Org. Biomol. Chem. 2011, 9, 5297. 5. Qiao Ren, Yaojun Gao, Jian Waanng. Chem. –Eur. J. 2010, 16, 13594. Ren Qiao 2014/003/07 Name Signature Date i PHD DISSERTATION 2013 REN QIAO Acknowledgements It is my great pleasure to express my deepest gratitude and appreciation to all the people who have helped and inspired me during my four-year PhD studies in Department of Chemistry, National University of Singapore (NUS).
    [Show full text]
  • The Development and SAR of Selective Sigma-2 Receptor Ligands for the Diagnosis of Cancer Mark Ashford University of Wollongong
    University of Wollongong Research Online University of Wollongong Thesis Collection University of Wollongong Thesis Collections 2010 The development and SAR of selective sigma-2 receptor ligands for the diagnosis of cancer Mark Ashford University of Wollongong Recommended Citation Ashford, Mark, The development and SAR of selective sigma-2 receptor ligands for the diagnosis of cancer, Doctor of Philosophy thesis, School of Chemistry, University of Wollongong, 2010. http://ro.uow.edu.au/theses/3634 Research Online is the open access institutional repository for the University of Wollongong. For further information contact the UOW Library: [email protected] The Development and SAR of Selective Sigma-2 Receptor Ligands for the Diagnosis of Cancer Mark E. Ashford B. Med. Chem. Hons (Adv) A thesis submitted in fulfilment of the requirements for the award of the degree Doctor of Philosophy From University of Wollongong School of Chemistry August 2010 Declaration I, Mark Edward Ashford, declare that this thesis, submitted in fulfilment of the requirements for the award of Doctor of Philosophy, in the School of Chemistry, Faculty of Science, University of Wollongong, is wholly my own work unless otherwise referenced or acknowledged. The document has not been submitted for qualifications at any other academic institution. Mark E. Ashford 2010 Mark Ashford, PhD Thesis 2010 ii Table of Contents Declaration.......................................................................................................................ii List of Figures.................................................................................................................vi
    [Show full text]
  • Quantification of Catalytic Activity for Electrostatically Enhanced Thioureas Via Reaction Kinetics and a UV−Vis Spectroscopic
    Quantification of Catalytic Activity for Electrostatically Enhanced Thioureas via Reaction Kinetics and a UV−Vis Spectroscopic Measurement Yang Fan, Curtis Payne and Steven R. Kass* Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, Minnesota 55455, United States E-mail: [email protected] Table of Content Graphic S R O N N R H N thiourea H Ph N O N CH2Cl2 N Ph Δλ < 0 max N N S S thiourea 10 thioureas examined, rates span >104 and blue shifts correlate with the rate 1 ABSTRACT Charged thiourea derivatives containing one and two methylated or octylated pyridinium ion centers and a tetraarylborate or triflate counteranion are reported. These novel catalysts are much more active in the Friedel‒Crafts reactions of trans-β-nitroalkenes with N-methylindoles than the privileged N,N'-bis(3,5-bis(trifluoromethyl)phenyl)thiourea (i.e., Schreiner’s thiourea) by up to 2-3 orders of magnitude. A previously reported UV-Vis spectroscopic method by Kozlowski et al. was exploited to rationalize their reactivity order along with non-charged analogs. These results offer a new design strategy for organocatalysts by introducing positively charged centers without adding additional N–H, O–H, or S–H hydrogen bond donor sites. 2 INTRODUCTION Nature exploits noncovalent interactions such as hydrogen bonds to reduce the activation energy barriers of enzyme-catalyzed chemical transformations.1 A wealth of small-molecule organocatalysts that mimic this behavior have been developed over the past two decades and this field has emerged
    [Show full text]
  • CV-PSB-August 2020
    Curriculum Vitae Phil S. Baran Appointment: Scripps Research Professor, Department of Chemistry 10550 North Torrey Pines Road, BCC-436 La Jolla, California 92037 Telephone: (858) 784-7373 Facsimile: (858) 784-7575 Email: [email protected] Website: www.scripps.edu/chem/baran/ January, 2013 Darlene Shiley Professor of Chemistry April, 2009 Member, Skaggs Institute for Chemical Biology June, 2008 Professor of Chemistry July, 2006 Associate Professor of Chemistry (with Tenure) June, 2003 Assistant Professor of Chemistry Date/Place of Birth: 10 Aug 1977 / Denville, NJ, USA Citizenship: United States Education 2001 – 2003 Postdoctoral Associate Advisor: Professor E.J. Corey Harvard University, Cambridge, Massachusetts 1997 – 2001 Ph.D. Graduate Student in Chemistry Advisor: Professor K.C. Nicolaou The Scripps Research Institute, La Jolla, California 1995 – 1997 B.S. with Honors in Chemistry Advisor: Professor D.I. Schuster New York University, New York, New York 1991 – 1995 Simultaneous high school graduation from Mt. Dora High School and A.A. degree with honors, Lake Sumter Community College, Florida Awards • Inhoffen Medal, 2019 • Manchot Research Professorship, 2017 • Member, The National Academy of Sciences, 2017 • Emanuel Merck Lectureship, 2017 • Blavatnik National Laureate in Chemistry, 2016 • ACS Elias J. Corey Award, 2016 • Member, American Academy of Arts and Sciences, 2015 • College of Arts and Science Alumni Distinguished Service Award, New York University, 2015 • Reagent of the Year Award (EROS), 2015 • Mukaiyama Award, 2014 •
    [Show full text]
  • New Reactions and Strategies in Divergent Syntheses of Macrolide Antibiotics
    NEW REACTIONS AND STRATEGIES IN DIVERGENT SYNTHESES OF MACROLIDE ANTIBIOTICS by LIBING YU A dissertation submitted to the Graduate School-New Brunswick Rutgers, The State University of New Jersey In partial fulfillment of the requirements For the degree of Doctor of Philosophy Graduate Program in Chemistry and Chemical Biology Written under the direction of Professor Lawrence J. Williams And approved by __________________________ __________________________ __________________________ __________________________ New Brunswick, New Jersey OCTOBER, 2015 ABSTRACT OF THE DISSERTATION New Reactions and Strategies in Divergent Syntheses of Macrolide Antibiotics By LIBING YU Dissertation Director: Professor Lawrence J. Williams From the microbial world, antibiotics are structurally complex and highly potent chemical weapons that co-evolved with bacteria. Macrolide (glycosylated cyclic polyketides) antibiotics have been used extensively as first-line antibacterial agents since the discovery of the broad-spectrum antibiotic erythromycin A in 1952. However wide- spread use of antibiotics has led pathogens to develop drug resistance. Therefore new and enhanced antibiotics are constantly in need. Described in this dissertation is my effort to emulate the synthetic capabilities of erythromycin-producing bacteria by accessing novel erythromycin-inspired polyketides via divergent total synthesis. New allene oxidation methods have been developed and implemented in a modular and divergent route to produce a diversified portfolio of cyclic polyketides and their glycoconjugates. I will disclose a total synthesis of 4,10- didesmethyl-(9S)-dihydroerythronolide A (Chapter 2), preparation of glycosylated erythromycin analogs (Chapter 3) and progress towards synthesis of 9(S)- dihydroerythronolide A (Chapter 4). ii Acknowledgements First and foremost, I would like to express my sincere gratitude to my advisor Professor Lawrence J.
    [Show full text]
  • 42 National Organic Chemistry Symposium Table of Contents
    42nd National Organic Chemistry Symposium Princeton University Princeton, New Jersey June 5 – 9, 2011 Table of Contents Welcome……………………………………………………………………………….......... 2 Sponsors / Exhibitors…..……………………………………………………………........... 3 DOC Committee Membership / Symposium Organizers………………………….......... 5 Symposium Program (Schedule)……...…………………………………………….......... 9 The Roger Adams Award…………………………………………………………….......... 14 Plenary Speakers………………………………………………………………………........ 15 Lecture Abstracts..…………………………………………………………………….......... 19 DOC Graduate Fellowships……………………………………………………………....... 47 Poster Titles…………………………...……………………………………………….......... 51 General Information..………………………………………………………………….......... 93 Attendees………………………………..……………………………………………........... 101 Notes………..………………………………………………………………………….......... 117 (Cover Photo by Chris Lillja for Princeton University Facilities. Copyright 2010 by the Trustees of Princeton University.) -------42nd National Organic Chemistry Symposium 2011 • Princeton University Welcome to Princeton University On behalf of the Executive Committee of the Division of Organic Chemistry of the American Chemical Society and the Department of Chemistry at Princeton University, we welcome you to the 42nd National Organic Chemistry Symposium. The goal of this biennial event is to present a distinguished roster of speakers that represents the current status of the field of organic chemistry, in terms of breadth and creative advances. The first symposium was held in Rochester NY, in December 1925, under the auspices of
    [Show full text]
  • Uva-DARE (Digital Academic Repository)
    UvA-DARE (Digital Academic Repository) Fluorogenic organocatalytic reactions Raeisolsadati Oskouei, M. Publication date 2017 Document Version Other version License Other Link to publication Citation for published version (APA): Raeisolsadati Oskouei, M. (2017). Fluorogenic organocatalytic reactions. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:01 Oct 2021 Chapter 1 1 Chapter 1 Introduction 1.1. Organocatalysis Catalyst, the term used to describe a compound that speeds up chemical reactions without being consumed: a world full of questions lies behind this simple term. Nearly all reactions that occur in living cells require catalysts and without them, life would be impossible, but what is the mechanism by which they work? What kind of catalysts are suitable to produce the desired products with high efficiency under mild conditions? How do they direct the reaction to a pathway which requires less activation energy? Many research groups attempt to discover the unknown aspects of the catalyst world.
    [Show full text]
  • Publications De L'ibmm
    Publications de l’IBMM de janvier 2014 à février 2021 2014.................................................................................................................................................................... 2 2015.................................................................................................................................................................. 15 2016.................................................................................................................................................................. 30 2017.................................................................................................................................................................. 44 2018.................................................................................................................................................................. 64 2019.................................................................................................................................................................. 83 2020................................................................................................................................................................ 104 2021................................................................................................................................................................ 126 2014 1. Morris, M. C., Spotlight on Fluorescent Biosensors-Tools for Diagnostics and Drug Discovery. Acs Medicinal Chemistry Letters 2014, 5 (2), 99-101.
    [Show full text]
  • Total Synthesis of (±)-Isodihydrokoumine, (±)-(19Z)-Taberpsychine, and (±)-Isodihydroukoumine N4 Oxide" (2018)
    Western University Scholarship@Western Electronic Thesis and Dissertation Repository July 2018 Total synthesis of (±)-isodihydrokoumine, (±)- (19Z)-taberpsychine, and (±)- isodihydroukoumine N4 oxide Jeff Kerkovius The University of Western Ontario Supervisor Kerr, Michael, A. The University of Western Ontario Graduate Program in Chemistry A thesis submitted in partial fulfillment of the requirements for the degree in Master of Science © Jeff Kerkovius 2018 Follow this and additional works at: https://ir.lib.uwo.ca/etd Part of the Organic Chemistry Commons Recommended Citation Kerkovius, Jeff, "Total synthesis of (±)-isodihydrokoumine, (±)-(19Z)-taberpsychine, and (±)-isodihydroukoumine N4 oxide" (2018). Electronic Thesis and Dissertation Repository. 5426. https://ir.lib.uwo.ca/etd/5426 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected], [email protected]. Abstract We report the total synthesis of the natural products (±)-isodihydrokoumine, and (±)- (19Z)-taberpsychine in 11 steps each, and (±)-isodihydrokoumine N4-oxide in 12 steps from commercially available starting materials. The key reactions include an intramolecular [3+2] nitrone cycloaddition, and Lewis acid mediated cyclizations of a common intermediate to provide the core structures of either (19Z)-taberpsychine or isodihydrokoumine. Both failed and successful routes will be discussed. Keywords Geleganidine A, Geleganidine B, koumine, taberpsychine, (19Z)-taberpsychine, koumidine, isodihydrokoumine, total synthesis, natural product, nitrone cycloaddition, cyclization chemistry, convergent synthesis, divergent synthesis i Acknowledgments I would like to thank my wife most of all for putting up with all of the late nights that I spent in the lab, and her unwavering support of my success during this project.
    [Show full text]
  • Concepts, Strategies, and Applications
    SOLID-PHASE ORGANIC SYNTHESIS Concepts, Strategies, and Applications Edited by Patrick H. Toy Yulin Lam ©WILEY A JOHN WILEY & SONS, INC., PUBLICATION CONTENTS Preface xv Acknowledgments xvii Contributors xix Part I CONCEPTS AND STRATEGIES 1 1 LINKER STRATEGIES IN MODERN SOLID-PHASE ORGANIC SYNTHESIS 3 Peter J. H. Scott 1.1 Introduction 3 1.2 Classical Linker Strategies 5 1.2.1 Acid and Base Cleavable Linker Units 5 1.2.2 Cyclorelease Linker Units 14 1.2.3 Traceless Linker Units 18 1.2.4 Photolabile Linker Units 21 1.2.5 Safety-Catch Linker Units 24 1.3 Multifunctional Linker Strategies 28 1.3.1 Nitrogen Linker Units 28 1.3.1.1 Triazene Linker Units 28 1.3.1.2 Hydrazone Linker Units 32 1.3.1.3 Benzotriazole Linker Units 34 1.3.2 Sulfur Linker Units 37 1.3.3 Phosphorus Linker Units 47 1.3.4 Selenium and Tellurium Linker Units 51 1.3.5 Silyl and Germyl Linker Units 54 1.3.6 Boron and Stannane Linker Units 63 1.3.7 Bismuth Linker Units 64 1.3.8 Alkene Linker Units 69 1.4 Conclusions 73 References 73 2 COLORIMETRIC TEST FOR SOLID-PHASE ORGANIC SYNTHESIS 83 Yan Teng and Patrick H. Toy 2.1 Introduction 83 2.2 Functional Group Tests 84 2.2.1 Amine Groups 84 2.2.1.1 Ninhydrin (Kaiser) Test 84 CONTENTS 2.2.1.2 TNBSA Test 84 2.2.1.3 Bromophenol Blue Test 84 2.2.1.4 Chloranil Test 85 2.2.1.5 DABITC Test 85 2.2.1.6 MGI Test 85 2.2.1.7 IsatinTest 85 2.2.1.8 DESCTest 86 2.2.1.9 NPIT Test 86 2.2.1.10 NF31 Test 86 2.2.1.11 Nondestructive NF31 Test 87 2.2.1.12 Naphthol Test 87 2.2.1.13 2-Amino-3-chloro-l,4-naphthoquinone Test 87 2.2.2 Alcohols 87 2.2.2.1
    [Show full text]