DOCSLIB.ORG

Alternative Formats If You Require This Document in an Alternative Format, Please Contact: [email protected]

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Alternative Formats If You Require This Document in an Alternative Format, Please Contact: Openaccess@Bath.Ac.Uk University of Bath PHD Ketene dithioacetals in synthesis Dziadulewicz, E. K. Award date: 1987 Awarding institution: University of Bath Link to publication Alternative formats If you require this document in an alternative format, please contact: [email protected] 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 ? Take down policy 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. Download date: 11. Oct. 2021 KETENE DITHIOACETALS IN SYNTHESIS Submitted by E. K. Dziadulewicz for the degree of PhD of the University of Bath 1987 Copyright 'Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without the prior written consent of the author'. 'This thesis may be made available for consultation within the University Library and may be photocopied or lent to other libraries for the purpose of consultation'. E. K. Dziadulewicz UMI Number: U601869 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U601869 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 univ:r; cr ..ath 9 V \ V " “ To my parents, for their constant support and encouragement. ACKNOWLEDGEMENTS The work described in this thesis was undertaken at the University of Bath from October 1983 to November 1986. I would like to thank my supervisor, Dr Tim Gallagher for his patience, guidance, and for supplying "motivation at the end of my boot" at those disheartening moments when black tars ruled the day, and a job with the local council's road-resurfacing division loomed on the horizon. The technical support staff also merit thanks. The laboratory technicians: Mrs S. Boucher, Mr R. Hunter and Mr R. Betteridge, who made the practical work possible; and the spectroscopic services: Mr D. Wood and Mr H. Hartell (^H and 13 C NMR spectroscopy), Mr C. Cryer (mass spectrometry), and Mr A. Carver (elemental microanalysis). I would also like to express my thanks to colleagues and friends for many helpful discussions, especially Dr D. Lathbury, and my co-workers on different aspects of this project, D. M. Hodgson and M. Giles. Professor A. McKervey, University College, Cork, is gratefully acknowledged for supplying a sample of 1, 3, 3 - tris (phenylthio) -1- propene (309) for comparative alkylation studies. Thanks are also due to Mrs P. Kielthy, Mrs E. Wharton and Mrs S. Biggs for some alchemy of their own; that of converting my manuscript to typescript, in a process that has been both qualitative and free of thiol odours. (i) Finally, I would like to thank the University of Bath for providing research facilities, and the SERC for provision of a research studentships Bath has presented an ideal setting for memorable and extremely enjoyable student days. (ii) Abstract This thesis is introduced by a comprehensive review of the major methods employed to functionalise the enone or acrylate structural unit at C-2 and C-3. Creation of a donor, anionic site at C-2 is electronically permissible, but is not attended without difficulties. The same operation at C-3 involves inverting the natural acceptor reactivity via use of synthetically equivalent reagents. In Section 2, the synthesis and metallation of a novel ketene dithioacetal is described. Lithiation of 1,1- bis(phenylthio)-3-phenylthio-l-propene and reaction with a variety of electrophiles gave exclusively the 'y -substituted products. Its use as a R-lithioacrylate equivalent in the construction of butenolides andy -lactones, is exemplified by a short synthesis of the long range sex attractant pheromone, (+)-eldanolide. A range of 1,1, 3-tr issulphur-substituted propenes was subsequently alkylated, and a study made of their regiochemical preferences? the predominance of CX - o r y - regioselectivity being dependent on the type of heteroatom substituents present. Bulky sulphur substituents at the Ol - carbon atom, such as phenyl, directed reaction to t hey - site. In those compounds in which steric effects were not so pronounced, reaction at the *y-site could be reinforced electronically by incorporating an alkyl or arylthio group at C-3. (iii) The feasibility of alkylating 1,1,3,3 -tetrakis (alkylthio)propenes was also tested. Successful reaction was only achieved with a novel bisdithiane-substituted propene. The acyclic analogues studied were all too sterically encumbered to accommodate electrophiles. This study was concluded with a synthesis of (+)-dihydrokawain, a plant constituent possessing a 5,6-dihydro-4-alkoxy-2H- pyran-2-one skeleton. The equivalency between the lithiated bisdithiane compound and ft-hydroxy -ft-lithioacrylate anion has been thereby established. (iv) ABBREVIATIONS The following abbreviations are used in the text DABCO 1,4-Diazabicyclo[2.2.2]octane DBN 1,5-Diazabicyclo[4.3.0.]non-5-ene DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene DCM Dichloromethane DME 1#2-Dimethoxyethane DMF N,N-Dimethylformamide DMPU N,N-Dimethylpropylene urea DMSO Dimethyl sulphoxide HMPA Hexamethylphosphoric triamide LDA Lithium N,N-diisopropylamide M Molar MCPBA meta-Chloroperoxybenzoic acid MEM Methoxyethoxymethylene, CH3 OCH2 CH2 OCH MOM Methoxymethylene, CH3 OCH2 - MTM Methylthiomethylene, CH3 SCH2 - NBS N-Bromosuccinimide NCS N-Chlorosuccinimide PTSA para-Toluene sulphonic acid py Pyridine Rf Retention factor ABBREVIATIONS TBDMSC1 tert-Butyldimethylsilyl chloride TFA Trifluoroacetic acid TMEDA N,N,N*,N'-Tetramethyl ethylene diamine TMSC1 Trimethylsilyl chloride (vi) CONTENTS Page ACKNOWLEDGEMENTS (±) ABSTRACT (iii) ABBREVIATIONS (v) CONTENTS (vii) 1 INTRODUCTION 1 1.1 The Concept of Synthetic Equivalency 1 1.2 The Functionalisation of the Acrylate 2 Unit and Related Derivatives 1.2.1 Introduction 2 o 1.2.2 Acrylate Anion d Reagents 5 1.2.3 Homoenolate Anion (d^) Reagents 40 1.2.3.1 Introduction 4 0 1.2.3.2 Acrylate Anion d Reagents 4 3 2 RESULTS AND DISCUSSION 86 2.1 Introduction 3 5 2.2 The Synthesis of 1,1,3-Tris(phenylthio) 3 3 -1-propene and its use as a |3-Lithioacrylate Equivalent 2.3 1,1,3-Trissulphur substituted propene 107 systems: The effect of altering the heteroatom substituents on the regiochemistry of alkylation 2.4 Metallation of 1,1,3,3 -Tetrakissulphur 126 substituted propene systems. The search for a $ -Hydroxy-0-1 ithioacrylate equivalent 2.5 Conclusion 145 2.6 Recommendations for Further Work 149 3 EXPERIMENTAL 156 4 PUBLICATIONS 208 5 REFERENCES AND NOTES 216 (vii) . INTRODUCTION * 1. INTRODUCTION 1.1 The Concept of Synthetic Equivalency For the synthesis of complex molecules, it is sometimes de­ sirable to have a specific reagent for the introduction of a given fragment or structural unit. The compound or idealised inter­ mediate actually required to carry out the direct synthetic operation may be inaccessible by normal or direct means, or in­ trinsically unstable. An effective strategy for the broadening of techniques for assembling collections of carbon atoms and functional groups is to use synthetically equivalent reagents or reaction series to perform identical transformations to these hypothetical compounds. The introduction of intact synthetically equivalent units is inherently attractive, because of the greater degree of convergency associated with this approach, a given unit often being supplied in a conveniently protected form. This latter feature is an important consideration in multistep syntheses of complex natural products, especially in the light of the high reactivity of some components, notably a,8-unsaturated acid deriva­ tives. Masking of a functional group may help to moderate the react­ ivity of a reagent, making it useable in the first instance, perhaps eliminating side reactions which might operate in the unmasked form. On the other hand, it is sometimes desirable to have synthons exhibiting reverse polarity at their reactive centres, to extend the general methodology of organic synthesis. These requirements must be translated into the design of reagents for practical use, and in Sections 1.2.2 and 1.2.3.2, the design of donor nucleophilic 1 sites at C-2, and the normally acceptor C-3 of the acrylate or enone unit is considered, via synthetically equivalent reagents. 1.2 The Functionalisation of the Acrylate Unit and Related Derivatives 1.2.1 Introduction The routine use, and widespread applicability, of the enone or acrylate moiety in carbon-carbon bond forming processes has a tendency to belie its importance in everyday synthetic operations. The possession of acceptor and dienophile properties, however, makes it a valuable synthetic agency in the construction or elabora­ tion of organic molecules.1 The fact that a relatively uncom­ plicated three-carbon unit can be functionalised at each carbon atom, potentially incorporating a total of four substituents, endows it with a versatility that has been utilised and expressed in another, more fundamental respect.
Load more

Recommended publications
  • Information to Users
    INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from 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. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. University Microfilms International A Bell & Howell Information C om pany 300 North Z eeb Road. Ann Arbor. Ml 48106-1346 USA 313/761-4700 800 521-0600 Order Number 9120692 Part 1. Synthesis of fiuorinated catecholamine derivatives as potential adrenergic stimulants and thromboxane A 2 antagonists. Part 2.
    [Show full text]
  • Synthesis of Aza-Heterocyclic Monoamidines As Potential DNA Minor Groove Binders, Anti-Trypanosomals, and Boron Neutron Capture Therapy Agents
    Georgia State University ScholarWorks @ Georgia State University Chemistry Dissertations Department of Chemistry Fall 12-17-2014 Synthesis of Aza-Heterocyclic Monoamidines as Potential DNA Minor Groove Binders, Anti-Trypanosomals, and Boron Neutron Capture Therapy Agents Julius Green Follow this and additional works at: https://scholarworks.gsu.edu/chemistry_diss Recommended Citation Green, Julius, "Synthesis of Aza-Heterocyclic Monoamidines as Potential DNA Minor Groove Binders, Anti- Trypanosomals, and Boron Neutron Capture Therapy Agents." Dissertation, Georgia State University, 2014. https://scholarworks.gsu.edu/chemistry_diss/101 This Dissertation is brought to you for free and open access by the Department of Chemistry at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Chemistry Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. SYNTHESIS OF AZA-HETEROCYCLIC MONOAMIDINES AS POTENTIAL DNA MINOR GROOVE BINDERS, ANTI-TRYPANOSOMALS, AND BORON NEUTRON CAPTURE THERAPY AGENTS by JULIUS GREEN I Under the Direction of David W. Boykin ABSTRACT A series of combilexin-like monoamidines has been synthesized by linking an intercala- tive unit with the DNA minor groove binder DB 818 via “Click chemistry.” DB 818 is a dicationic minor groove binder that has shown strong binding affinity to AT sequences. The aim was to synthesize novel classes of DNA minor groove binders that are combilexin-like – minor groove binder / intercalator hybrid – as potential unique DNA binding agents and therapeutics against African Sleeping Sickness. Additionally, a series of novel benzo[d]1,3,2-diazaboroles DAPI derivatives were also synthesized and investigated. These boron compounds have the po- tential to be strong DNA minor groove binders because of their lower pK a and act as potential chromophores for Boron Neutron Capture Therapy.
    [Show full text]
  • A New Late-Stage Lawesson's Cyclization Strategy Towards The
    A NEW LATE-STAGE LAWESSON’S CYCLIZATION STRATEGY TOWARDS THE SYNTHESIS OF ARYL 1,3,4-THIADIAZOLE-2-CARBOXYLATE ESTERS A thesis submitted to the Kent State University Honors College in partial fulfillment of the requirements for Departmental Honors by Michael Joseph Schmidt August, 2013 TABLE OF CONTENTS LIST OF FIGURES.............................................................................................................v LIST OF TABLES...........................................................................................................viii ACKNOWLEDGEMENTS................................................................................................ix CHAPTER 1. INTRODUCTION.......................................................................................1 1.1 Introduction to liquid crystals and their phases...............................1 1.1.1 Liquid crystal phases........................................................................2 1.1.2 Interaction of liquid crystals with electric fields and polarized light..................................................................................5 1.2 Ferroelectric liquid crystals (FLCs) and their applications in liquid crystals displays (LCDs)....................................................8 1.2.1 Molecular structure of ferroelectric liquid crystals........................12 1.3 The synthesis of 1,3,4-thiadiazoles in liquid crystal materials......15 1.3.1 Ring-forming approaches to 1,3,4-thiadiazoles and other five-membered aromatic S-heterocycles........................................16
    [Show full text]
  • Design of Sensors for Highly Phosphorylated Natural Compounds
    Design of sensors for highly phosphorylated natural compounds Dissertation Submitted for the Degree Doctor rerum naturalium (Doctor rer. nat.) at the Faculty of Chemistry and Pharmacy University of Freiburg by Rahel Hinkelmann Rheinfelden (Baden) 2020 Vorsitzender des Promotionsausschusses: Prof. Dr. Stefan Weber Dekan: Prof. Dr. O. Einsle Referent/in: Prof. Dr. H. J. Jessen Korreferent/in: Prof. Dr. M. Müller Datum der mündlichen Prüfung: 30.10.2020 Abstract Highly phosphorylated metabolites, e.g. inositol polyphosphates (InsPs), diphospho- inositol phosphates (PP-InsPs), inorganic polyphosphate (polyP) and Magic spot nu- cleotides (MSN) regulate various biological processes. Their distinctive role in biology remain still elusive particularly concerning their dynamic turnover. The investigation of their contributions in metabolic processes asks for the development of, in vivo and in vitro, real time analytical detection. In this work the design, synthesis and evaluation of a set of new fluorescent chemosen- sors is presented, since inositol polyphosphates and polyP are lacking an intrinsic chro- mophore. The synthesized chemosensors can be divided into the following three cate- gories - Pyrene-excimer based, disassembly approach and DAPI derivatives. A 4’,6-diamidin-2-phenylindol (DAPI) synthesis was developed in this work. The photo- physical properties of the respective set of synthesized chemosensors in combination with the above mentioned phosphorylated metabolites was evaluated. Fe3+-Salen and PyDPA was successfully used as a polyacrylamide gel electrophoresis (PAGE) stain and the latter dye was applied as a post-column staining reagent for Ins(1,2,3,4,5,6)-hexakisphosphate (InsP6) on an ion chromatography system. In addition, the investigation and appli- cation of a new 31P-NMR based method using a chiral solvating agent revealed the stereoselectivity of the first described naturally occurring 1-phytase.
    [Show full text]
  • Design, Synthesis and Analysis of Potential Photo-Activatable Cathepsin K Inhibitors" (2017)
    Wayne State University Wayne State University Theses 1-1-2017 Design, Synthesis And Analysis Of Potential Photo- Activatable Cathepsin K Inhibitors Khalin Evania Nisbett Wayne State University, Follow this and additional works at: https://digitalcommons.wayne.edu/oa_theses Part of the Biochemistry Commons, Inorganic Chemistry Commons, and the Organic Chemistry Commons Recommended Citation Nisbett, Khalin Evania, "Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors" (2017). Wayne State University Theses. 581. https://digitalcommons.wayne.edu/oa_theses/581 This Open Access Thesis is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Theses by an authorized administrator of DigitalCommons@WayneState. DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS by KHALIN EVANIA NISBETT THESIS Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE 2017 CHEMISTRY Approved By: ___________________________________ Jeremy Kodanko, Ph.D. Date ©COPYRIGHT BY KHALIN EVANIA NISBETT 2017 All Rights Reserved Dedication I know the Lord is always with me. I will not be shaken, for he is right beside me. -Psalm 16:8 ii Acknowledgements “The Lord is my shepherd; I shall not want. He maketh me to lie down in green pastures: he leadeth me beside the still waters. He restoreth my soul: he leadeth me in the paths of righteousness for his name’s sake. Yea, though I walk through the valley of the shadow of death, I will fear no evil: for thou art with me; thy rod and thy staff they comfort me.
    [Show full text]
  • Synthesis and Evaluation of Polyamines As Antimalarial Agents
    Synthesis and Evaluation of Polyamines as Antimalarial Agents A Thesis submitted in part fulfilment of the requirements of the degree of Doctor of Philosophy Lindsay Anne Slater Department of Chemistry University of Glasgow Glasgow G12 8QQ March 1998 ProQuest Number: 13815441 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 13815441 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 GLASGOW UNIVERSITY LIBRARY (H O t GLASGOW UNIVERSITY UB3ARY mmm malaria (moqeorio) n. an infectious disease characterized by recur­ ring attacks of chills and fever, caused by the bite of an anopheles mosquito infected with any of four protozoans of the genus Plasma - dium (P . vivax, P. falciparum, P. malariae, or P. ovale), [€18; from Ita lia n mala aria bad air, from the belief that the disease was caused by the unwholesome air in swampy districts] —ma'Iarial, m a’larian, or ma’Iarious adj. Acknowledgements 1 would like to thank David Robins for his help and advice throughout the last few years and especially for his guidance when presenting this thesis (grammar!).
    [Show full text]
  • SYNTHESIS, STRUCTURAL and BIOLOGICAL STUDIES of POTENTIAL 5-HT3 RECEPTOR ANTAGONISTS. BRENDAN A. WHELAN Ph.D. 1994
    SYNTHESIS, STRUCTURAL AND BIOLOGICAL STUDIES OF POTENTIAL 5-HT3 RECEPTOR ANTAGONISTS. BRENDAN A. WHELAN Ph.D. 1994 SYNTHESIS, STRUCTURAL AND BIOLOGICAL STUDIES OF POTENTIAL 5-HT3 RECEPTOR ANTAGONISTS. bv* Brendan /I.lA/h&Un, A Thesis presented to Dublin City University for the degree of Doctor of Philosophy. This work was carried out under the supervision of Dr. Paraic James at Dublin City University, Dublin and Dr. Enrique Galvez at Universidad de Alcala de Henares, Madrid. December 1994 mt? anc^ mtf/ parents (linttoy and /Cathie&n. I hereby certify that this material, which I now submit for assessment on the programme of study leading to the award of PhD is entirely my own work and has not been taken from the work of others save and to the extent that such work has been cited and acknowledged within the text of my own work Candidate Date: I ' tf></- Adnou/iedgements / wouid fiile to begin bp expressing my* pr-a.titu.dle, to mp superu-isor Or, Paraic (James a t Dublin City* {/(nio-ersitp and to Or.Fnritjue (jdbez and Dr. /satfriepa a t th e iyfniu-ersitp ofr Ahatfa de- nenareSj Madrid, To (lose, Sanz-Aporicio and /sabetf Fonseca / woutfd tfi£e to g/Ve mp than is faor collaborating with the X~rap studies and to Antonio Orga^es ofi F.A .F .S, ltd . faor the phar-mac oiogiG a / studies. liietoise, to Dr.tfracia (yfceda and Or, Antonio (jar cl a faor the, biochemical assays. Sincere thanis to affl mp department coffleagues and stafafa mem hers at A^caia.
    [Show full text]
  • Vol.31 No. 11 RUSSIAN CHEMICAL REVIEWS November 1962
    Vol.31 No. 11 RUSSIAN CHEMICAL REVIEWS November 1962 evidently due to the ready polarisability of the cyano-group; also the presence of acids creates suitable conditions for REACTIONS OF NITRILES WITH HYDROGEN the appearance of electrophilic activity at the nitrile car- HALIDES AND NUCLEOPHILIC REAGENTS bon atom and the formation of new bonds between this atom and atoms of oxygen, sulphur, nitrogen, carbon, etc. Ε. Ν. Zil'berman Hydrogen halides are particularly important as acid catalysts for reactions of the cyano-group, and in many CONTENTS cases, especially with hydrogen chloride, they are specific 615 catalysts. The Pinner reaction (preparation of imidate I. Introduction salts), Hoesch reaction (preparation of ketimine salts), Gattermann reaction, Stephen reaction (preparation of Π. Reactions of nitriles with hydrogen halides 615 aldimine salts), and several other acid-catalysed reactions A. Nitrile hydrohalides of composition RCN.ηΗΧ 615 of nitriles are carried out in the presence of hydrogen halides, and do not occur with other protogenic or Lewis B. Some properties of solutions of hydrogen acids in the absence of hydrogen halides. In the literature halides in nitriles 617 these reactions are very often discussed without considera- tion of the nature of the products of the reaction of nitriles C. Nitrile hydrohalides of composition 2RCN.nHX 618 with hydrogen halides, which may be formed under the D. Preparation of 1, 3, 5-triazines 618 experimental conditions. These products are often for- mulated as imidoyl halides, although these have never been E. Hydrogen cyanide hydrohalides 619 isolated and there is no proof of their existence in the reac- ΠΙ.
    [Show full text]
  • Synthesis of Natural and Non-Natural Polycylic Alkaloids by Adam Thomas Hoye B.A., Grinnell College, 2004 Submitted to the Grad
    Synthesis of Natural and Non-Natural Polycylic Alkaloids by Adam Thomas Hoye B.A., Grinnell College, 2004 Submitted to the Graduate Faculty of Arts and Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Pittsburgh 2010 UNIVERSITY OF PITTSBURGH SCHOOL OF ARTS AND SCIENCES This thesis was presented by Adam Thomas Hoye It was defended on August 16th, 2010 and approved by Professor Dennis P. Curran, Department of Chemistry Professor Paul E. Floreancig, Department of Chemistry Professor Billy W. Day, Department of Pharmaceutical Sciences Dissertation Advisor: Professor Peter Wipf, Department of Chemistry ii Copyright © by Adam Thomas Hoye 2010 iii Synthesis of Natural and Non-Natural Polycylic Alkaloids Adam T. Hoye, PhD University of Pittsburgh, 2010 Part one of this dissertation describes the synthesis of novel polycyclic natural product- like compounds from dicyclopropylmethylamine starting materials. Using methodology previously developed in our group, products from the initial one-pot multicomponent reaction via the rearrangement of a bicyclo[1.1.0]butane intermediate were successfully transformed into polycyclic systems. These small, medium and large heterocycles mimic complex alkaloids found in nature, and were further elaborated to incorporate additional functionalities. Part two describes our investigation into the parvistemonine class of Stemona alkaloids. We developed a unified strategy to target several related Stemona natural products. A [3,3]- sigmatropic rearrangement was used to relay key stereochemical information across the characteristic pyrrolo[1,2-a]azepine core of these molecules and install contiguous stereocenters in a controlled fashion. This approach produced advanced intermediates towards the syntheses of parvistemonine and sessilifoliamides B and D, and culminated in the first enantioselective total syntheses of sessilifoliamide C and 8-epi-stemoamide.
    [Show full text]
  • Acetonitrile As a Building Block and Reactant
    10.1055/s-0036-1589535 ss-2018-e0191-r review Acetonitrile as a Building Block and Reactant B. H. Hoff Biographical Sketches e0191_helgehoff.eps Bård Helge Hoff was born in Oslo, Norway in 1971. He received his Master’s degree in 1995, followed by a Ph.D. in 1999 working with Professor Thorleif Anthonsen in the field of biocatalysis. In 2000 he joined Borregaard Synthesis, Norway, where he worked as a researcher and team leader until the end of 2005. In 2006 he joined the Department of Chemistry at the Norwegian University of Science and Technology, Trondheim, Norway as associate professor. He became full professor in 2016. Awards include Outstanding OIDD collaborator: Blinded synthesis award 2016 from Eli Lilly, the ‘Gullegget’ innovation prize from NTNU Technology Transfer Office in 2013, and an award for young organic chemists in Norway in 2011 by the Norwegian Chemical Society. His research is within the field of applied organic chemistry with the main activity in medicinal chemistry. He has lately also entered the field of organic electronic materials. Previous research includes biocatalysis, asymmetric synthesis, fluorinated building blocks, carbohydrate chemistry, cellulose and lignin chemistry, heterocyclic chemistry, and cross-coupling methodology. Department of Chemistry, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, 7491 Trondheim, Norway [email protected] ■■check changes to English■■ Received: 20.03.2018 Accepted after revision: 19.04.2018 Abstract e0191_ga.eps Acetonitrile is popular as a solvent for performing organic reactions, as a ligand in inorganic chemistry, as a mobile phase in chromatography, and as an electrolyte solvent in dye-sensitized solar cells.
    [Show full text]
  • A Comprehensive Review of the Covalent Immobilization of Biomolecules Onto Electrospun Nanofibers
    nanomaterials Review A Comprehensive Review of the Covalent Immobilization of Biomolecules onto Electrospun Nanofibers Soshana Smith 1,* , Katarina Goodge 1 , Michael Delaney 2, Ariel Struzyk 2, Nicole Tansey 1 and Margaret Frey 1 1 Department of Fiber Science and Apparel Design, Cornell University, Ithaca, NY 14853, USA; [email protected] (K.G.); [email protected] (N.T.); [email protected] (M.F.) 2 Robert Frederick Smith School of Chemical & Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA; [email protected] (M.D.); [email protected] (A.S.) * Correspondence: [email protected] Received: 7 October 2020; Accepted: 21 October 2020; Published: 27 October 2020 Abstract: Biomolecule immobilization has attracted the attention of various fields such as fine chemistry and biomedicine for their use in several applications such as wastewater, immunosensors, biofuels, et cetera. The performance of immobilized biomolecules depends on the substrate and the immobilization method utilized. Electrospun nanofibers act as an excellent substrate for immobilization due to their large surface area to volume ratio and interconnectivity. While biomolecules can be immobilized using adsorption and encapsulation, covalent immobilization offers a way to permanently fix the material to the fiber surface resulting in high efficiency, good specificity, and excellent stability. This review aims to highlight the various covalent immobilization techniques being utilized and their benefits and drawbacks. These methods typically fall into two categories: (1) direct immobilization and (2) use of crosslinkers. Direct immobilization techniques are usually simple and utilize the strong electrophilic functional groups on the nanofiber. While crosslinkers are used as an intermediary between the nanofiber substrate and the biomolecule, with some crosslinkers being present in the final product and others simply facilitating the reactions.
    [Show full text]
  • Baclofean Via Fe(Acac)3 Catalyzed Michael Addition and Pinner Reaction
    Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2015, 7(10):466-469 ISSN : 0975-7384 Research Article CODEN(USA) : JCPRC5 A facile synthesis of (±)-Baclofean via Fe(acac) 3 catalyzed Michael addition and Pinner reaction Manojkumar U. Chopade a* and Anil U. Chopade b aSant Dnyaneshwar Mahavidyalaya, Department of Chemistry, Soegaon, Dist: Aurangabad, Dr. Babasaheb Ambedkar Marathwada University Aurangabad, Maharashtra, India bDahiwadi College, Dahiwadi, Rayat Shikshan Sansthan, Satara, Shivaji University Kolhapur, Maharashtra, India _____________________________________________________________________________________________ ABSTRACT An effective and convenient procedure for the Michael addition using Fe (acac) 3 (1 mol %) as an effective catalyst, catalyses the Michael addition reaction of nitro methane to α-cyano cinnamate ester followed by Pinner reaction to produce corresponding diethyl 2-(1-(4-chlorophenyl)-2-nitroethyl)malonate with good yields under mild condition with high yield. Accordingly, we applied this synthetic strategy for synthesis of (±)-Baclofean. NO2 NH2.HCl CN Catalyst COOEt COOH COOEt COOEt Cl Cl Cl (±)-Baclofen 5 Michael addition of nitromethane to an α-cyano cinnamate ester is a key step for the synthesis of (±)-baclofen. Keywords: Michael addition; Fe(acac) 3; Nitro methane; α-Cyano cinnamic ester, Amino acids. _____________________________________________________________________________________________ INTRODUCTION The transition metal(TM) catalysis plays an important role in modern organic chemistry [1]. The most of the reaction catalyzed by Lewis acid are stoichiometric therefore, recently have great attention towards the transition metal catalyzed reaction in synthetic chemistry due to their numerous advantages low cost, nontoxic or interesting catalytic activity, reaction proceed cleanly with high efficiency and easy to handle, at ambient reaction condition without formation of salt.
    [Show full text]