DOCSLIB.ORG

The Development and SAR of Selective Sigma-2 Receptor Ligands for the Diagnosis of Cancer Mark Ashford University of Wollongong

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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 List of Schemes .............................................................................................................viii List of Tables ...................................................................................................................x Abbreviations .................................................................................................................xi Publications and Presentations ...................................................................................xiv Acknowledgements........................................................................................................xv Abstract.........................................................................................................................xvi 1. Introduction.............................................................................................................1 1.1. Sigma Receptors................................................................................................1 1.2. Sigma Receptor Subtypes..................................................................................2 1.2.1. Sigma-1 Receptor..............................................................................................2 1.2.2. Sigma-2 Receptor..............................................................................................3 1.3. Synthetic Sigma-2 Ligands ...............................................................................3 1.4. Sigma-2 Receptor Function...............................................................................4 1.4.1. Apoptosis ..........................................................................................................4 1.5. The role of Sigma-2 Receptors in Disease........................................................5 1.5.1. Cancer ...............................................................................................................5 1.6. Classes of Sigma-2 Ligands..............................................................................6 1.6.1. Spiro and Phenylpiperidines..............................................................................7 1.6.2. Azabicyclic Ligands..........................................................................................8 1.6.3. Benzamide Analogues.......................................................................................9 1.7. Radiopharmaceutical Chemistry.....................................................................11 1.7.1. Radionuclides..................................................................................................11 1.7.2. Radiopharmaceuticals .....................................................................................12 1.7.3. Imaging Modalities .........................................................................................14 1.8. Radiolabelled Sigma-2 Ligands......................................................................15 1.8.1. 123 I Labelled Ligands.......................................................................................16 1.9. Project Aims....................................................................................................17 2. Synthesis of Region 3 Aromatic Derivatives.......................................................19 2.1. Rationale for targeted compounds...................................................................19 2.2. SAR of Region 3.............................................................................................19 2.3. Synthesis of the key intermediate 4-((3,4-dihydro-6,7-dimethoxyisoquinolin- 2(1 H)-yl)methyl)piperidine-1-yl)amine [34] ..................................................21 2.4. Amine coupling reactions and preparation of [36] ..........................................23 2.5. Synthesis of the 4-((3,4-dihydro-6,7-dimethoxyisoquinolin-2(1 H)- yl)methyl)piperidine-1-yl) amides with region 3 modification ......................24 2.5.1. Non-halogenated amides.................................................................................24 Mark Ashford, PhD Thesis 2010 iii 2.6. Halogenated amides........................................................................................26 2.6.1. Synthesis of 5-iodobenzofuran-2-carboxylic acid [44] ...................................29 2.7. Synthesis of target halogenated amides ..........................................................33 2.8. In vitro binding of amide derivatives..............................................................35 2.9. Lipophilicity Estimates ...................................................................................39 2.10. Attempted further modification to Region 3...................................................39 2.11. Conclusion ......................................................................................................40 3. Synthesis of Region 2 Carbon Spacer Derivatives.............................................42 3.1. Modification of Region 2................................................................................42 3.2. General Synthetic Strategy..............................................................................43 3.3. Synthesis of flexible benzamide intermediates...............................................44 3.3.1. Synthesis of target amines [70] -[72] ...............................................................44 3.4. Synthesis of flexible spacer target amides [73] -[78] .......................................46 3.5. In vitro studies and log P.................................................................................50 3.6. Amides with semi-rigid spacers......................................................................52 3.6.1. Synthesis of key amines [90] and [91] ............................................................53 3.6.2. Synthesis of target compounds [92] -[95] with a ethyl- or propylpiperidine spacer.....................................................................................................…….55 3.7. Synthesis of propylpiperazine target compound [102] ....................................56 3.7.1. Method 1: Synthesis of amine intermediate [101] via the Boc protected piperazine [99] ................................................................................................57 3.7.2. Method 2: Synthesis of piperazine [101] via the benzyl protected piperazine [100] ..............................................................................................………….60 3.8. Synthesis of target amide [104] .......................................................................63 3.9. In vitro studies and log P.................................................................................64 3.10. Conclusions and future directions...................................................................65 4. Synthesis of Region 3 Isoquinoline Derivatives..................................................67 4.1. Rationale .........................................................................................................67 4.2. Isoquinoline Synthesis ....................................................................................67 4.3. Formation of isoquinoline intermediates ........................................................73 4.3.1. Synthesis of conformationally flexible intermediates using isoquinolines [105] , [108] and [115a] . .................................................................................73 4.3.2. Synthesis of conformationally semi-restricted intermediates using isoquinolines [108] and [115a] .......................................................................74 4.4. Synthesis and in vitro evaluation of amides with region 3 modification........75 4.4.1. Synthesis of target flexible spacer amides [134] -[136] and semi-rigid amides [137] -[138] .....................................................................................................75
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]
  • 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]
  • 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]
  • Organic Synthesis
    Edited by Belakatte Parameshwarappa Nandeshwarappa The book ‘Organic Synthesis - A Nascent Relook’ is a compendium of the recent Organic Synthesis - A Nascent Relook progress in all aspects of organic chemistry including bioorganic chemistry, organo- metallic chemistry, asymmetric synthesis, heterocyclic chemistry, natural product Organic Synthesis chemistry, catalytic, green chemistry and medicinal chemistry, polymer chemistry, as well as analytical methods in organic chemistry. The book presents the latest A Nascent Relook developments in these fields. The chapters are written by chosen experts who are internationally known for their eminent research contributions. Organic synthesis is the complete chemical synthesis of a target molecule. In this book, special emphasis is given to the synthesis of various bioactive heterocycles. Careful selection of various Edited by topics in this book will serve the rightful purpose for the chemistry community and Belakatte Parameshwarappa Nandeshwarappa the industrial houses at all levels. ISBN 978-1-78985-943-0 Published in London, UK © 2020 IntechOpen © nespix / iStock Organic Synthesis - A Nascent Relook Edited by Belakatte Parameshwarappa Nandeshwarappa Published in London, United Kingdom Supporting open minds since 2005 Organic Synthesis - A Nascent Relook http://dx.doi.org/10.5772/intechopen.83193 Edited by Belakatte Parameshwarappa Nandeshwarappa Contributors Tejpal Singh Chundawat, Naga Sesha Sai Pavan Kumar Chebolu, Yan-Chao Wu, Yun-Fei Cheng, Hui-Jing Li, Davor Margetić, Vjekoslav Štrukil, Badri Nath Jha, Abhinav Raghuvanshi, Nishant Singh, Vitaliy Viktorovich Libanov, Alevtina Anatol’evna Kapustina, Nikolay Pavlovich Shapkin, Tangali Ramanaik Ravikumar Naik, Andivelu Ilangovan, Adarsh Krishna Thumadath Palayullaparambil, Sakthivel Pandaram, Tamilselvan Duraisamy, Jamel Mejri, Youkabed Zarrouk, Majdi Hammami, David Joshua Ferguson © The Editor(s) and the Author(s) 2020 The rights of the editor(s) and the author(s) have been asserted in accordance with the Copyright, Designs and Patents Act 1988.
    [Show full text]
  • EV Andreitchenko's Dissertation, Mainz 2006
    Extended Arm Polyphenylene Dendrimers: Synthesis and Characterization Dissertation zur Erlangung des Grades ‚‚Doktor der Naturwissenschaften’’ am Fachbereich Chemie und Pharmazie der Johannes Gutenberg-Universität in Mainz vorgelegt von Ekaterina Vladimirovna Andreitchenko geb. in Sankt-Petersburg, Russland Mainz, 2006 Die vorliegende Arbeit wurde in der Zeit von Mai 2002 bis November 2005 am Max-Planck- Institut für Polymerforschung in Mainz unter der Leitung von Prof. Dr. K. Müllen durchgeführt. Herrn Professor Dr. K. Müllen danke ich für die sehr interessante Themenstellung and für seine wissenschaftliche Förderung. Contents 1 Introduction 1.1 The dendrimer concept 1 1.2 Chemical synthesis of dendrimers 2 1.3 Flexible dendrimers 5 1.4 Molecular structure 5 1.5 Properties of dendritic macromolecules compared to linear polymers 7 1.6 Rigid dendrimers 8 1.7 Synthesis of polyphenylene dendrimers through Diels-Alder cycloaddition 10 1.7.1 Divergent synthesis 12 1.7.2 Convergent synthesis 12 1.8 The influence of the cores and the branching units on the shape of the polyphe- nylene dendrimers 15 1.9 Functionalization of polyphenylene dendrimers 16 a) Prior group introduction, the cyclopentadienone route 17 b) Posteriori Group Introduction 19 c) Electrophilic Aromatic Substitution 19 1.10 Practical applications of dendrimers 20 1.11 Motivation 21 1.12 Literature for Chapter 1 24 2 Extended Arm Polyphenylene Dendrimers 2.1 Introduction 28 2.2 Synthesis of the new branching unit 2.1 bearing tris-(para -phenylene ethynylene)arms 28 2.3 Synthesis
    [Show full text]
  • Guidebook for the Synthesis of Oligonucleotides Product Guide 2015/16
    Guidebook for the Synthesis of Oligonucleotides Product Guide 2015/16 www.linktech.co.uk | +44 (0) 1698 849911 | [email protected] Don’t let paperwork Synthesis of oligonucleotides is Opening an online account with LINK is slow down the real complicated enough without the chore easy – and you can place your first order work. of ordering reagents getting in the way. in minutes. Popular products are always Buying oligo reagents from LINK is held in stock, ensuring a fast and Order reagents in simple and straightforward. In the time reliable turnaround from order to seconds for next-day it takes to download a couple of music delivery. And, for many common tracks online, you could be sorted for products, highly attractive multi-pack delivery. next-day delivery, anywhere in mainland discounts are available immediately Europe. online – there’s no need to request a Our extensive catalogue of products for quote. the synthesis of oligonucleotides All of which leaves you to concentrate (including DNA, RNA, PNA and UNA on making your oligos. While we products) has all the reagents you need. concentrate on making your life easier. What’s more, our quality control ensures impeccable consistency of product. Find out more: www.linktech.co.uk | +44 (0) 1698 849911 | [email protected] Guidebook for the Synthesis of Oligonucleotides Product Guide 2015/16 © 2015 Link Technologies Ltd. Unless otherwise specified, no content from this document may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without the prior written permission of Link Technologies Ltd.
    [Show full text]
  • Divergent Rhodium-Catalyzed Electrochemical Vinylic C–H Annulation of Acrylamides with Alkynes
    Divergent Rhodium-Catalyzed Electrochemical Vinylic C–H Annulation of Acrylamides with Alkynes Yi-Kang Xing Shanghai Institute of Organic Chemistry Xin-Ran Chen Zhejiang University Qi-Liang Yang Henan Normal University Shuoqing Zhang Zhejiang University https://orcid.org/0000-0002-7617-3042 Haiming Guo Henan Normal University Xin Hong Zhejiang University https://orcid.org/0000-0003-4717-2814 Tian-Sheng mei ( [email protected] ) Shanghai Institute of Organic Chemistry https://orcid.org/0000-0002-4985-1071 Article Keywords: Undivided Cell, Regioselectivities, Unsymmetrical Alkynes, Seven-membered Ring Vinyl- rhodium Intermediate, α-pyridones, Cyclic Imidates Posted Date: October 26th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-92513/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Divergent Rhodium-Catalyzed Electrochemical Vinylic C–H Annulation of Acrylamides with Alkynes Yi-Kang Xing,1,4 Xin-Ran Chen,2,4 Qi-Liang Yang,3,4 Shuo-Qing Zhang,2 Hai-Ming Guo,3 Xin Hong,2,* and Tian-Sheng Mei1,* 1State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS, Shanghai, China 2Department of Chemistry, Zhejiang University, Hangzhou, 310027, China 3Henan Key Laboratory of Organic Functional Molecules and Drug Innovation, Henan Normal University, Xinxiang, Henan, China 4Contributed equally to this work *Correspondence: [email protected]; [email protected] Abstract A Rh-catalyzed electrochemical vinylic C–H annulation of acrylamides with alkynes has been developed in an undivided cell, affording cyclic products in good to excellent yield. Divergent syntheses of -pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively.
    [Show full text]