DOCSLIB.ORG

WO 2014/113634 Al 24 July 2014 (24.07.2014) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2014/113634 Al 24 July 2014 (24.07.2014) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2014/113634 Al 24 July 2014 (24.07.2014) P O P C T (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/22 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/US20 14/0 11985 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 17 January 2014 (17.01 .2014) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/753,690 17 January 2013 (17.01.2013) U S kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicant: UNIVERSITY OF KANSAS [US/US]; 245 UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, Strong Hall, 1450 Jayhawk Boulevard, Lawrence, KS TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 66045 (US). EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (72) Inventors: SALUNKE, Deepak, B.; 245 Strong Hall, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, 1450 Jayhawk Boulevard, Lawrence, KS 66045 (US). KM, ML, MR, NE, SN, TD, TG). GUO, Xiaoqiang; 245 Strong Hall, 1450 Jayhawk Boulevard, Lawrence, KS 66045 (US). DAVID, Sunil, A.; Published: 245 Strong Hall, 1450 Jayhawk Boulevard, Lawrence, KS — with international search report (Art. 21(3)) 66045 (US). — before the expiration of the time limit for amending the (74) Agent: ZACHARIADES, Nicholas, A.; Duane Morris claims and to be republished in the event of receipt of LLP, 5 100 Town Center Circle, Suite 650, Boca Raton, FL amendments (Rule 48.2(h)) 33486 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (54) Title: TOLL-LIKE RECEPTOR 2-AGONISTIC LIPOPEPTIDES, AND METHOD OF MAKING THE SAME FIG. (57) Abstract: The present disclosure is directed to a novel class of toll-like receptor 2-agnonistic (TLR2) lipopeptide compounds having specific structures, and synthetic methods of making the compounds. These compounds provide high potency of agonistic activities with human, other than murine, TLR2, and are useful as vaccine adjuvants. Vaccines are perhaps one of the most success - ful medical interventions against infectious disease. TOLL-LIKE RECEPTOR 2-AGONISTIC LIPOPEPTIDES, AND METHOD OF MAKING THE SAME CROSS-REFERENCE TO RELATED APPLICATIONS [001] The present application claims priority to US provisional application serial number 61/753,690 filed on January 17, 2013 which is incorporated herein by reference in its entirety. STATEMENT OF FEDERAL FUNDING [002] This invention was made with government support under federal contract number HHSN272200900033C, awarded by the National Institutes of Health. The government has certain rights in the invention. FIELD OF THE INVENTION [003] Embodiments are provided that are directed to synthetic methods for making toll-like receptor 2-agonistic (TLR2) lipopeptides, resulting compounds or compositions comprising TLR2 lipopeptides, and use of such compounds or compositions as vaccine adjuvants. BACKGROUND [004] Vaccines are perhaps one of the most successful medical interventions against infectious disease. An important component in the design of effective vaccines is the incorporation of appropriate immune potentiators (also termed adjuvants) along with the antigen; adjuvants initiate early innate immune responses, which lead to the induction of robust and long- lasting adaptive immune responses. More than eight decades have elapsed since the discovery of adjuvanticity of aluminum salts (primarily phosphate and hydroxide) and the repertoire of investigational adjuvants has grown to encompass a very wide range of materials; however, aluminum salt-based mineral salts (generically, and incorrectly, termed "alum") have, until the recent introduction of 3-0-desacyl-4'-monophosphoryl lipid A (MPL), remained the only adjuvants currently approved by the FDA. Aluminum salts have enjoyed a good safety record but are weak adjuvants for antibody induction, promoting a TH2-skewed, rather than a T 1 response. Furthermore, not only are aluminum salts ineffective at inducing cytotoxic T lymphocyte (CTL) or mucosal IgA antibody responses but also have an undesirable propensity to induce IgE isotype switching, which has been associated with allergic reactions in some subjects (Relyveld, E. H., et al. Vaccine 1998, 16, 1016-1023; Gupta, R. K. Adv. Drug Delivery Rev. 1998, 32, 155-172). [005] Toll-like receptors (TLRs) are pattern recognition receptors present on diverse cell types. TLRs recognize specific molecular patterns present in molecules that are broadly shared by pathogens but are sufficiently different so as to be distinguishable from host molecules and are collectively referred to as pathogen-associated molecular patterns (PAMPs). There are 10 TLRs in the human genome; these are transmembrane proteins with an extracellular domain having leucine-rich repeats (LRR) and a cytosolic domain called the ToU/IL-1 receptor (TIR) domain (Kumagai, Y. et al. J. Infect. Chemother. 2008, 14, 86-92). [006] The ligands for these receptors are highly conserved microbial molecules such as lipopolysaccharides (LPS) (recognized by TLR4), lipopeptides (TLR2 in combination with TLR1 or TLR6), flagellin (TLR5), single-stranded RNA (TLR7 and TLR8), double-stranded RNA (TLR3), CpG motif-containing DNA (recognized by TLR9), and profilin present on uropathogenic bacteria (TLR 11) (Kumagai, Y. et al J. Infect. Chemother. 2008, 14, 86-92; Takeda, K. Akira, S. Curr. Protoc. Immunol. 2007, Chapter 14, Unit 14, p 12). TLR1, -2, -4, -5, and -6 respond to extracellular stimuli, while TLR3, -7, -8, and -9 respond to intracytoplasmic PAMPs, being associated with the endolysosomal compartment (Kumagai, Y. et al. Infect. Chemother. 2008, 14, 86-92). The activation of TLRs by their cognate ligands leads to production of inflammatory cytokines, and up-regulation of MHC molecules and costimulatory signals in antigen-presenting cells as well as activating natural killer (NK) cells (innate immune response), in addition to priming and amplifying T- and B-cell effector functions (adaptive immune responses) (Akira, S. Adv. Immunol. 1902, 78, 1-56; Akira, S. et al. Nature Immunol. 2001, 2, 675-680; Cottalorda, A. et al. Eur. J. Immunol. 2006, 36, 1684-1693; Kaisho, T. et al. Biochim. Biophys. Acta 2002, 1589, 1-13). SUMMARY [007] This summary is provided to briefly indicate the nature and substance of the present disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. [008] Toll-like receptor (TLR) stimuli serve to link innate and adaptive immunity and can therefore be exploited as powerful adjuvants in eliciting both primary and anamnestic immune responses. Embodiments are directed to a novel class of compounds of toll-like receptor 2- agonistic (TLR2) lipopeptides, resulting compositions comprising such compounds, synthetic methods for making the compounds, and method of use of such compounds or compositions as vaccine adjuvants. [009] In some embodiments, the present disclosure provides a composition comprising a compound of general formula I : wherein: L is a functional group comprising: -C(0)-0-, -O-C(O)-, -C(O)-, -C(0)-NH-, -NH- C(O)-, -NH-C(0)-0-, -0-C(0)-NH-, alkyl, d -20 alkyl, C2-20 alkenyl, C2-20 alkynyl, C4-20 heterocycle, C4-2oheteroaryl, C4-20 alkyl heterocycle, C -20 alkyl heteroaryl and Cj- 20 alkyoxyl, urea, esters, inverse esters, a keto group, amides, inverse amides, carbamate groups, inverse carbamate groups, wherein the Ci-20 alkyl, C2-20 alkenyl, C2-20 alkynyl, C4-2oheterocycle, C4-20 heteroaryl, C4-20 alkyl heterocycle, C -20 alkyl heteroaryl, Ci-20 alkyoxyl, and the -6 alkyl is unsubstituted or optionally substituted with a functional group comprising H, -OH, -OR' , -NH2, -NHR\ - R ' , -SH, -SR', -0-C(0)R', -C(0)R', -CF3, -OCF3, and an amino acid side chain, the -20 alkyl, C2-20 alkenyl, C2-20 alkynyl, C -20 heterocycle, C4-20 heteroaryl, C4-2o alkyl heterocycle, C -20 alkyl heteroaryl, C^o alkyoxyl, and the - alkyl is optionally interrupted by one or more O, S, or N atoms, or one or more groups selected from cycloalkyl, -C(0)-0-, -O-C(O)-, -C(O)-, -C(0)-NH-, -NH-C(O)-, -NH-C(0)-0- and -0-C(0)-NH-, and R' is selected from radicals consisting of H, heteroaryl having 1 to 4 N, O and/or S atoms, -io alkyl, C2-io alkenyl, C2-10 alkynyl, C4-10 heterocycle and C - 10 heteroaryl; Ri is H or -5o alkyl, the Ci- 50 alkyl is unsubstituted or optionally substituted with a functional group selected from the group consisting of H, -OH, -OR', -NH2, -NHR', -NR' 2, -SH, -SR', -0-C(0)R', -C(0)R', -CF3, -OCF 3, an amino acid side chain or peptide fragment, where R' is selected from radicals consisting of H, heteroaryl having 1 to 4 N, O and/or S atoms, alkyl, C2- 0 alkenyl, C - o alkynyl, C -10 heterocycle and C4-10 heteroaryl; R2 is H, a natural or unnatural amino acid side chain, polar or non-polar groups and S- or R-enantiomers thereof.
Load more

Recommended publications
  • Transport of Dangerous Goods
    ST/SG/AC.10/1/Rev.16 (Vol.I) Recommendations on the TRANSPORT OF DANGEROUS GOODS Model Regulations Volume I Sixteenth revised edition UNITED NATIONS New York and Geneva, 2009 NOTE The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. ST/SG/AC.10/1/Rev.16 (Vol.I) Copyright © United Nations, 2009 All rights reserved. No part of this publication may, for sales purposes, be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical, photocopying or otherwise, without prior permission in writing from the United Nations. UNITED NATIONS Sales No. E.09.VIII.2 ISBN 978-92-1-139136-7 (complete set of two volumes) ISSN 1014-5753 Volumes I and II not to be sold separately FOREWORD The Recommendations on the Transport of Dangerous Goods are addressed to governments and to the international organizations concerned with safety in the transport of dangerous goods. The first version, prepared by the United Nations Economic and Social Council's Committee of Experts on the Transport of Dangerous Goods, was published in 1956 (ST/ECA/43-E/CN.2/170). In response to developments in technology and the changing needs of users, they have been regularly amended and updated at succeeding sessions of the Committee of Experts pursuant to Resolution 645 G (XXIII) of 26 April 1957 of the Economic and Social Council and subsequent resolutions.
    [Show full text]
  • Hazardous Substances (Chemicals) Transfer Notice 2006
    16551655 OF THURSDAY, 22 JUNE 2006 WELLINGTON: WEDNESDAY, 28 JUNE 2006 — ISSUE NO. 72 ENVIRONMENTAL RISK MANAGEMENT AUTHORITY HAZARDOUS SUBSTANCES (CHEMICALS) TRANSFER NOTICE 2006 PURSUANT TO THE HAZARDOUS SUBSTANCES AND NEW ORGANISMS ACT 1996 1656 NEW ZEALAND GAZETTE, No. 72 28 JUNE 2006 Hazardous Substances and New Organisms Act 1996 Hazardous Substances (Chemicals) Transfer Notice 2006 Pursuant to section 160A of the Hazardous Substances and New Organisms Act 1996 (in this notice referred to as the Act), the Environmental Risk Management Authority gives the following notice. Contents 1 Title 2 Commencement 3 Interpretation 4 Deemed assessment and approval 5 Deemed hazard classification 6 Application of controls and changes to controls 7 Other obligations and restrictions 8 Exposure limits Schedule 1 List of substances to be transferred Schedule 2 Changes to controls Schedule 3 New controls Schedule 4 Transitional controls ______________________________ 1 Title This notice is the Hazardous Substances (Chemicals) Transfer Notice 2006. 2 Commencement This notice comes into force on 1 July 2006. 3 Interpretation In this notice, unless the context otherwise requires,— (a) words and phrases have the meanings given to them in the Act and in regulations made under the Act; and (b) the following words and phrases have the following meanings: 28 JUNE 2006 NEW ZEALAND GAZETTE, No. 72 1657 manufacture has the meaning given to it in the Act, and for the avoidance of doubt includes formulation of other hazardous substances pesticide includes but
    [Show full text]
  • The Reactions Between Acid Halides and Aldehydes
    L. H. Ulich The R eacfions bef^vreen /\cid Hali'oles cinc( Aldehydes THE REACTIONS BETWEEN ACID HALIDES AND ALDEHYDES BY LYNNE HERMAN ULICH B. S. Grinnell College, 1914 M. S. University of Illinois, 19 18 THESIS Submitted in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY IN CHEMISTRY IN THE GRADUATE SCHOOL OF THE UNIVERSITY OF ILLINOIS 1920 UNIVERSITY OF ILLINOIS THE GRADUATE SCHOOL May 11 i9g0 I HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY. Lynne Herman Ulioh ENTITLED THE REACTION S BETWEEN ACID HAL IDES AND ALDEHYDES BE ACCEPTED AS FULFILLING THIS PART OF THE REQUIREMENTS FOR THE DEGREE of Doctor of Philosophy In Charge of Thesis V Head of Department Recommendation concurred in* Committee on Final Examination* ^Required for doctor's degree but not for master's TABLE 0._F CONTENTS Page No. ACCTOWLEDG .1 TUT I. INTRODUCTION 1 II. HISTORICAL PART 3 III. THEORETICAL PART 11 IV. EXPERIMENTAL P'PT 23 A. Reactions of Aliphatic Acid Halides and Aliphatic Aldehyde$35 1. With Para Formaldehyde 35 2. With Paraldehyde 30 3. With Ieo-ontyl Aldehyde 35 4. Tith Iso-v^leryl Aldehyde 39 5. With Hfptaldehyde 41 B. Reactions of Aromatic Acid Halides and Aliphatic Aldehydes^ 1 . With Par a For maid ehyd a 43 2. With Paraldehyde 45 3. With n -Butyl Aldehyde 45 4. With Iso-valeryl -Aldehyde 46 5. mth Heptaldehyde 47 0. Reactions of the Addition Compounds 49 1. With Ammonia and Amines 49 3. ir ith T-Vater 52 3. With Solid Potassium Hydroxide 52 4.
    [Show full text]
  • The Reactions of Aliphatic Acid Chlorides Norman 0
    THE REACTIONS OF ALIPHATIC ACID CHLORIDES NORMAN 0 . V . SONNTAG Colgate-Palmolive-Peet Company. Jersey City. New Jersey Received November 16. 1962 CONTENTS I . Introduction .................. ......................................... 238 I1. Scope of the revieL1. ....................................................... 239 I11 . Nomenclature ............................................. IV . Reduction of aliphatic acid chlorides ...................... A . The Rosenmund reduction., ............................................ 245 B . Catalytic hydrogenation .............................................. 247 C . Chemical methods of reduction ....................................... 248 1. With sodium amalgam .......................................... 2 . With metal hydrides ................................................ 249 3 . With other reducing agents ........................................ 251 V . Hydrolysis of aliphatic acid chlorides ....................................... 251 VI . Reaction of aliphatic acid chlorides with ammonia, hydroxylamine, and hy- drazine ................................................................... 258 A . Reaction with ammonia .............................................. 258 1. At low temperatures............................................... 258 2 . At high temperatures ................................................ 265 B . Reaction with hydroxylamine and hydrazine.,........................... 266 VI1. Reaction of aliphatic acid chlorides with amines, substituted amines, and re- lated compounds
    [Show full text]
  • Fume Hood Safety by Eliminating All Bench-Level Obstructions
    INCREASING FUME HOOD SAFETY BY ELIMINATING ALL BENCH-LEVEL OBSTRUCTIONS Synthcon, LLC | 770 Wooten Rd., Unit 101, CO Springs, CO 80915 | 719.429.5376 Copyrighted Material © 2021 The Problem is Fume Exhaust Abstract This document will discuss the Pathway Obstruction importance of understanding Fume hoods are, first and foremost, safety devices. Their use should what affects efficient fume be carefully thought out to fit the user's specific needs. An amazing exhaustion from a chemical fume variety and quantity of equipment is often seen being used inside a hood and how to maximize the fume hood. Surprisingly, most volatile chemicals used inside a fume effectiveness of any existing fume hood produce vapors more dense than air; dense vapors will tend to hood by integrating a simple, sink while exiting the fume hood. Unfortunately, many bench single engineering control safety surfaces contain equipment that severely impedes direct, efficient measure to assure maximum fume exhaustion (airflow). This practice is so wide spread that it has exhaustion in any fume hood use become second nature to scientists who use fume hoods. The photograph above shows what a bench surface should and can look scenario. This new category of like with the same equipment still being used inside the hood, but safety devices is leading the way with the hood's lab bench surface free of equipment and chemical toward safer fume hood use for obstructions. More on this patent-pending, new category of safety all users. devices later in the paper. Let's take a closer look at the problem and then the solution.
    [Show full text]
  • Tesi Federica Porta
    Department of Pharmaceutical Sciences PhD Course in Pharmaceutical Sciences -XXIX Cycle- Design, synthesis and biological evaluation of novel antiproliferative compounds as potential anticancer agents Tutor: Prof. Alessandro Pedretti Coordinator: Prof. Marco De Amici Federica Porta R10459 Academic year 2015/2016 It is not the most intellectual or the strongest species that survives, but the species that survives is the one that is able to adapt to or adjust best to the changing environment in which it finds itself. Attributed to Charles Darwin Abstract Selectivity for cancer cells is one of the most important characteristics of anticancer agents. The transition from cytotoxic chemotherapy to molecularly targeted cancer drug discovery and development resulted in an increasing number of successful therapies that impacted the lives of a large number of cancer patients. The extreme toxicity and the development of resistance have made it essential to keep searching for new potential targeted anticancer agents, endowed with higher efficacy and minor toxicity. In order to achieve this goal, I followed different approaches: - starting from antiproliferative compounds, I sought their molecular target; - developing STAT3 inhibitors, I obtained dual-target compounds with enhanced cytotoxicity; - employing computationally driven drug design, I investigated new chemical scaffolds, able to disrupt STAT3 dimerization and characterized by suitable drug-like properties. 1,2,5-Oxadiazoles have received considerable attention in recent years from Prof. Barlocco’s research group because of the interesting results as potential antitumor agents. Among all, MD77 displayed a very interesting antiproliferative profile. Therefore, I focused my research efforts in the identification of its molecular target employing a combined synthetic-computational approach.
    [Show full text]
  • ANALYSIS of ALTERNATIVES Public Version
    ANALYSIS OF ALTERNATIVES Public Version Legal name of applicant: LANXESS Deutschland GmbH Submitted by: LANXESS Deutschland GmbH Substance: 1,2-Dichloroethane (EDC) EC Number: 203-458-1 CAS Number: 107-06-2 Use title: Use 1: Industrial use as a swelling agent during the sulphonation reaction of polystyrene-divinylbenzene copolymer beads in the manufacturing of strong acid cation exchange resins Use 2: Industrial use as a swelling agent and reaction medium during the phthalimidomethylation reaction of polystyrene-divinylbenzene copolymer beads in the manufacturing of anion exchange and chelating resins Use numbers: 1 and 2 Copyright ©2016 LANXESS Deutschland GmbH. This document is the copyright of LANXESS Deutschland GmbH and is not to be reproduced or copied without its prior authority or permission. Disclaimer This report has been prepared by Risk & Policy Analysts Ltd, with reasonable skill, care and diligence under a contract to the client and in accordance with the terms and provisions of the contract. Risk & Policy Analysts Ltd will accept no responsibility towards the client and third parties in respect of any matters outside the scope of the contract. This report has been prepared for the client and we accept no liability for any loss or damage arising out of the provision of the report to third parties. Any such party relies on the report at their own risk. Table of contents 1 Summary .............................................................................................................................. 1 1.1 Background to this analysis of alternatives .................................................................................... 1 1.2 Identification of potential alternatives for EDC and overall feasibility ........................................... 2 1.3 Technical feasibility of potential alternatives for EDC .................................................................... 3 1.4 Economic feasibility of potential alternatives for EDC ..................................................................
    [Show full text]
  • Chemical Identification of Contaminants in Paper and Board Food Contact Materials
    Downloaded from orbit.dtu.dk on: Dec 21, 2017 Chemical identification of contaminants in paper and board food contact materials Bengtström, Linda; Petersen, Jens Højslev; Granby, Kit; Trier, Xenia Publication date: 2014 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Bengtström, L., Petersen, J. H., Granby, K., & Trier, X. (2014). Chemical identification of contaminants in paper and board food contact materials. Kgs. Lyngby: Technical University of Denmark (DTU). General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Chemical identification of contaminants in paper and board food contact materials Linda Bengtström PhD Thesis 2014 Chemical identification of contaminants in paper and board food contact materials PhD Thesis Linda Bengtström Division of Food Chemistry National
    [Show full text]
  • Hazardous Chemicals Handbook
    Hazardous Chemicals Handbook Hazardous Chemicals Handbook Second edition Phillip Carson PhD MSc AMCT CChem FRSC FIOSH Head of Science Support Services, Unilever Research Laboratory, Port Sunlight, UK Clive Mumford BSc PhD DSc CEng MIChemE Consultant Chemical Engineer Oxford Amsterdam Boston London New York Paris San Diego San Francisco Singapore Sydney Tokyo Butterworth-Heinemann An imprint of Elsevier Science Linacre House, Jordan Hill, Oxford OX2 8DP 225 Wildwood Avenue, Woburn, MA 01801-2041 First published 1994 Second edition 2002 Copyright © 1994, 2002, Phillip Carson, Clive Mumford. All rights reserved The right of Phillip Carson and Clive Mumford to be identified as the authors of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988 No part of this publication may be reproduced in any material form (including photocopying or storing in any medium by electronic means and whether or not transiently or incidentally to some other use of this publication) without the written permission of the copyright holder except in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 90 Tottenham Court Road, London, England W1T 4LP. Applications for the copyright holder’s written permission to reproduce any part of this publication should be addressed to the publishers British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloguing
    [Show full text]
  • Preparation of Allylic Ketones Via Acylation of Allylic Mercurials ; And
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1991 Preparation of allylic ketones via acylation of allylic mercurials ; and, Palladium(0)-catalyzed coupling of aryl iodides, nonconjugated dienes, and nucleophiles Yong-de Lu Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Lu, Yong-de, "Preparation of allylic ketones via acylation of allylic mercurials ; and, Palladium(0)-catalyzed coupling of aryl iodides, nonconjugated dienes, and nucleophiles " (1991). Retrospective Theses and Dissertations. 9660. https://lib.dr.iastate.edu/rtd/9660 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. UMI MICROFILMED 1992 INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly fi-om the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion.
    [Show full text]