DOCSLIB.ORG

Phosphonites As New Chemoselective Modification Tools in Staudinger

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Phosphonites As New Chemoselective Modification Tools in Staudinger Phosphonites as new Chemoselective Modification Tools in Staudinger Reactions Dissertation zur Erlangung des akademischen Grades des Doktors der Naturwissenschaften (Dr. rer. nat.) Eingereicht im Fachbereich Biologie, Chemie, Pharmazie der Freien Universität Berlin Vorgelegt von Moritz Robert Johannes Vallée aus Hamburg 2013 Die Arbeit wurde zwischen dem 02.06.2009 und 06.10.2013 unter der Leitung von Prof. Dr. Christian P. R. Hackenberger im Institut für Chemie und Biochemie der Freien Universität Berlin sowie am Leibniz-Institut für Molekulare Pharmakologie (FMP) angefertigt. 1. Gutachter: Prof. Dr. Christian P. R. Hackenberger 2. Gutachter: Prof. Dr. Rainer Haag Disputation am 31.10.2013 Declaration I herewith confirm that I have prepared this dissertation without the help of any impermissible resources. All citations are marked as such. The present thesis has neither been accepted in any previous doctorate degree procedure nor has it been evaluated as insufficient. Berlin, 06th October 2013 M. Robert J. Vallée The work on this dissertation resulted so far in the following publications: 1. M. R. J. Vallée, Lukas M. Artner, Jens Dernedde and Christian P. R. Hackenberger, Angew. Chem. Int. Ed. 2013, 52, 9504–9508. / Angew. Chem. 2013, 125, 9682–9686. Alkyne phosphonites for sequential azide-azide couplings DOI: 10.1002/anie201302462 2. V. Böhrsch, T. Mathew, M. Zieringer, M. R. J. Vallée, L. M. Artner, J. Dernedde, R. Haag, C. P. R. Hackenberger, Org. Biomol. Chem. 2012, 10, 6211-6216. Chemoselective Staudinger-phosphite reaction of symmetrical glycosyl-phosphites with azido-peptides and polygycerols DOI: 10.1039/c2ob25207d 3. M. R. J. Vallée, P. Majkut, I. Wilkening, C. Weise, G. Muller, C. P. R. Hackenberger, Org. Lett.2011 , 13, 5440-5443. Staudinger-Phosphonite Reactions for the Chemoselective Transformation of Azido- Containing Peptides and Proteins DOI: 10.1021/ol2020175 Acknowledgments I would like to say a big thank you to all of the people who were involved in my project and without them I would have never been able to finish this work: To my supervisor Prof. Christian Hackenberger, for giving me the opportunity to work in his group on this very fascinating topic; for leaving me all the freedom to develop my ideas and allowing me to conduct experiments on my own without interference. I would like to thank him for all his support during the years, that made life in the group so comfortable, as well as his ambitions to show us the world of chemistry outside the lab. Prof. Dr. Rainer Haag for being my second referee and for the support given by him and his group, especially Cathleen Schlesener and Maximilian Zieringer. My second supervisor Prof. Christopf Schalley for helpful discussions and supporting my work. All current and former members of the Hackenberger group for positive and encouraging debates and also for the good working atmosphere, which have turned the last years into great time. Special thanks go to Paul Majkut, který se stal mým dobrým kamarádem a se kterým jsme strávili mnoho hodin u jezera, vytvářejíce mosty mezi chemií a biochemií, My friend and lab colleagues Lukas Artner, Verena Börsch and Michaela Mühlberg for creating such a nice working environment in the lab that mades work fun, as well as the great times outside the lab. Katrin Wittig for taking away all bureaucratic affairs from me and always having a positive outlook. Volker Rohde, Gregor Müller, Sebastian Wieczorek, Aryaline Kamalakumar and Jan-Hinnerk Saathoff who have worked with me on this project during their Bachelor theses or internships. Dr. Christoph Weise and Dr. Jens Dernedde who both spent many days and nights rescuing the sinking ship with a lot of patience and faith. Dr. Andreas Schäfer, Dr. Peter Schmieder and Brigitte Schlegel from the NMR-facilities of the Freie Universität and the FMP, for their helpful discussions and support with all the NMR desires. Dr. Andreas Springer and Fabian Klautzsch for all the advice and knowledge towards ESI-TOF use and for solving many unexpected problems. RiNA GmbH for supporting me with material and knowledge concerning unnatural proteins and biochemical experiments – performed by Paul Majkut. Dagmar Krause for all the HPLC purifications and LCMS analysis she did for me. Dr. Siegfried Wilkening for taking his time to proofread this thesis. I would like to express my greatest gratitude to Dr. Ina Wilkening, my friend, the most honest, altruistic and helpful person I have ever met, who supported me very much in every step throughout this work. Ina Abbreviation Ac acetyl b]pyridinium 3-oxid hexafluorophosphate AU adsorbance units HBTU 2-(1H-benzotriazole-1-yl)-1,1,3,3- BCN bicyclo[6.1.0]nonyne tetramethyluronium Bn benzyl hexafluorophosphate calcd. calculated HOBt 1-hydroxybenzotriazole CuAAC copper-catalyzed alkyne-azide HOMO highest occupied molecular coupling orbital d day HPLC high performance liquid Da Dalton chromatography dba dibenzylideneacetone HRMS high resolution mass spectrometry DBU 1,8-diazabicyclo[5.4.0]undec-7- ene ICP-MS inductively coupled plasma mass spectrometry DCM dichloromethane LCMS liquid chromatography–mass Dde N-(1-(4,4-dimethyl-2,6- spectrometry dioxocyclohexylidene)ethyl) LRMS low resolution massspectrome try Dec decyl LUMO lowest unoccupied molecular DIBO dibenzocyclooctyne orbital DIFO difluorocyclooctyne Me methyl DIPEA N,N-diisopropylethylamine MeCN acetonitrile DMF dimethylformamide min minutes DMSO dimethyl sulfoxide mOEG oligoethylene glycol monomethyl DNA 2’-desoxyribonucleic acid ether ee enantiomeric excess MP melting point e. g. exempli gratia MS mass spectrometry ER endoplasmic reticulum n. d. not detected ESI electrospray ionization NBD 4-amino-7-nitrobenzo-2-oxa-1,3- Et ethyl diazole Fmoc fluorenylmethyloxycarbonyl NCL native chemical ligation GFP green fluorescent protein NMP N-methyl-2-pyrrolidon h hours NMR nuclear magnetic resonance HATU 1-[bis(dimethylamino)- s singulett methylene]-1H-1,2,3-triazolo[4,5- d doublet t triplett q quartet quint quintet m multiplett J scalar coupling constant Pap p-azidophenylalanine PEG polyethylene glycol PG protecting group / poly glycerol Ph phenyl pin pinacol pKa acid dissociation constant iPr isopropyl PTM posttranslational modification R residue RCM ring closure metathesis RNA ribonucleic acid s second SPAAC strain-promoted alkyne-azide cycloaddition TEA triethylamine Tf triflate TFA trifloroacetic acid THF tetrahydrofuran THPTA tris(3-hydroxypropyl- triazolylmethyl)amine TIC total ion count TIS triisopropylsilane TLC thin layer chromatography TMA trimethylamine TOF time of flight Ts tosyl UV ultraviolet Table of contents 1 Introduction ....................................................................................... 1 1.1 From phosphorus to phosphites and phosphonites .................................................1 1.1.1 Synthesis of phosphites and phosphonites ................................................................ 2 1.1.2 Reactions of phosphites and phosphonites ............................................................... 5 1.2 The Staudinger reaction ....................................................................................... 10 1.2.1 Reaction mechanism ................................................................................................12 1.2.2 Staudinger ligation ...................................................................................................16 1.2.3 Staudinger reaction as chemoselective modification tool for biomolecules ...........19 1.3 Functionalization of biomolecules and polymers................................................... 24 1.3.1 Modifications of proteins through natural occurring functional groups .................25 1.3.2 Modifications of biomolecules through unnatural functional groups .....................27 1.3.2.1 Introduction of an unnatural functional group into proteins ..................................28 1.3.2.2 Chemoselective functionalization reactions for biomolecules ................................30 1.3.3 Functionalization of polymers ..................................................................................34 2 Objective .......................................................................................... 39 3 Discussion......................................................................................... 43 3.1 Retrosynthetic evaluation of functionalised phosphonite synthesis ....................... 45 3.2 Aryl phosphonites for the functionalization of peptides and proteins .................... 51 3.3 Alkyne phosphonites for sequential azide-azide couplings in organic solvents ....... 57 3.4 Alkyne phosphonites as modification tool for peptides and proteins ..................... 65 3.4.1 Syntheses of triazole phosphonites for applications in aqueous systems ...............66 3.4.2 Hydrolysis of triazole phosphonites .........................................................................72 3.4.3 Staudinger reactions of triazole phosphonites in aqueous systems ........................73 3.4.3.1 Quantification of the Staudinger-phosphonite reaction by fluorophore- tagged azido peptides ..............................................................................................75 3.4.3.2 Quantification of the Staudinger-phosphonite reaction by mass spectrometry ...........................................................................................................84 3.4.4 Biotinylation of Rasa1-N via Staudinger-phosphonite reaction ...............................95 3.5 Synthesis of coumarin
Load more

Recommended publications
  • 14.8 Organic Synthesis Using Alkynes
    14_BRCLoudon_pgs4-2.qxd 11/26/08 9:04 AM Page 666 666 CHAPTER 14 • THE CHEMISTRY OF ALKYNES The reaction of acetylenic anions with alkyl halides or sulfonates is important because it is another method of carbon–carbon bond formation. Let’s review the methods covered so far: 1. cyclopropane formation by the addition of carbenes to alkenes (Sec. 9.8) 2. reaction of Grignard reagents with ethylene oxide and lithium organocuprate reagents with epoxides (Sec. 11.4C) 3. reaction of acetylenic anions with alkyl halides or sulfonates (this section) PROBLEMS 14.18 Give the structures of the products in each of the following reactions. (a) ' _ CH3CC Na| CH3CH2 I 3 + L (b) ' _ butyl tosylate Ph C C Na| + L 3 H3O| (c) CH3C' C MgBr ethylene oxide (d) L '+ Br(CH2)5Br HC C_ Na|(excess) + 3 14.19 Explain why graduate student Choke Fumely, in attempting to synthesize 4,4-dimethyl-2- pentyne using the reaction of H3C C'C_ Na| with tert-butyl bromide, obtained none of the desired product. L 3 14.20 Propose a synthesis of 4,4-dimethyl-2-pentyne (the compound in Problem 14.19) from an alkyl halide and an alkyne. 14.21 Outline two different preparations of 2-pentyne that involve an alkyne and an alkyl halide. 14.22 Propose another pair of reactants that could be used to prepare 2-heptyne (the product in Eq. 14.28). 14.8 ORGANIC SYNTHESIS USING ALKYNES Let’s tie together what we’ve learned about alkyne reactions and organic synthesis. The solu- tion to Study Problem 14.2 requires all of the fundamental operations of organic synthesis: the formation of carbon–carbon bonds, the transformation of functional groups, and the establish- ment of stereochemistry (Sec.
    [Show full text]
  • Catalytic Ethylene Dimerization and Oligomerization Speiser Et Al
    Acc. Chem. Res. 2005, 38, 784-793 reaktion)2 of ethylene, nickel salts could modify the nature Catalytic Ethylene Dimerization of the products from R-olefins to 1-butene. This phenom- and Oligomerization: Recent enon became known in the literature as ªthe nickel effectº1,3 and led to the discovery of the ªZiegler catalysisº4 Developments with Nickel and to the remarkable chemistry developed by Wilke and 5 others over decades. The selective synthesis of C4-C20 Complexes Containing linear R-olefins has become a topic of considerable P,N-Chelating Ligands interest in both academia and industry owing to their growing demand most notably as comonomers with ² ,² FREDY SPEISER, PIERRE BRAUNSTEIN,* AND ethylene [C4-C8 to yield branched linear low-density LUCIEN SAUSSINE³ polyethylene (LLDPE) with impressive rheological and Laboratoire de Chimie de Coordination (UMR 7513 CNRS), mechanical properties6], for the synthesis of poly-R-olefins Universite Louis Pasteur, 4 rue Blaise Pascal, F-67070 and synthetic lubricants (C ), as additives for high-density Strasbourg CeÂdex, France, and Institut Franc¸ais du PeÂtrole, 10 Direction Catalyse et SeÂparation, IFP-Lyon, BP 3, F-69390 polyethylene production and for the production of plas- 7-9 Vernaison, France ticizers (C6-C10) and surfactants (C12-C20). The annual 8 Received February 14, 2005 worldwide consumption of polyolefins is close to 10 tons. Because the demand for linear R-olefins is growing faster - × 6 ABSTRACT in the C4 C10 range (a ca. 2.5 10 tons/year market) than Catalytic ethylene oligomerization represents a topic of consider- in the C12+ range, the selective formation from ethylene able current academic and industrial interest, in particular for the of specific shorter chain R-olefins, which could circumvent R - production of linear -olefins in the C4 C10 range, whose demand the typical, broad Schulz-Flory distributions observed in is growing fast.
    [Show full text]
  • When Phosphosugars Meet Gold: Synthesis and Catalytic Activities of Phostones and Polyhydroxylated Phosphonite Au(I) Complexes
    Article When Phosphosugars Meet Gold: Synthesis and Catalytic Activities of Phostones and Polyhydroxylated Phosphonite Au(I) Complexes Gaëlle Malik, Angélique Ferry and Xavier Guinchard * Received: 23 September 2015 ; Accepted: 20 November 2015 ; Published: 27 November 2015 Academic Editor: Bimal Banik Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, 1 Avenue de la Terrasse, 91198 Gif sur Yvette cedex, France; [email protected] (G.M.); [email protected] (A.F.) * Correspondence: [email protected]; Tel.: +33-1-69-82-30-66 Abstract: The synthesis and characterization of P-chiral phosphonite-, phosphonate- and thiophosphonate-Au(I) complexes are reported. These novel ligands for Au(I) are based on glycomimetic phosphorus scaffolds, obtained from the chiral pool. The catalytic activities of these complexes are shown in the cyclization of allenols and the hydroamination of 2-(2-propynyl)aniline combined with an organocatalyzed reduction to the corresponding 2-phenyl tetrahydroquinoline. All described gold complexes present excellent catalytic activities. Keywords: gold catalysis; phosphosugars; catalysis; heterocycles; P-stereogeny 1. Introduction One of the major advances of the 21th century in organic chemistry is undoubtedly the increased importance of gold catalysis. Long believed to be useless for catalysis, gold complexes have emerged as powerful tools for the catalysis of myriads of reactions [1–9]. In particular, the gold tolerance towards air, moisture and numerous chemical functionalities renders the use of these catalysts very convenient. However, the bicoordinate linear geometry of gold(I) complexes makes the control of the asymmetry difficult, the chiral ligand being placed in a distal position to the reactive cationic center.
    [Show full text]
  • S1 Supporting Information Copper-Catalyzed
    Supporting Information Copper-Catalyzed Semihydrogenation of Internal Alkynes with Molecular Hydrogen Takamichi Wakamatsu, Kazunori Nagao, Hirohisa Ohmiya*, and Masaya Sawamura* Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan Table of Contents Instrumentation and Chemicals S1 Characterization Data for Alkynes S1–S2 Procedure for the Copper-Catalyzed Semihydrogenation of Alkynes S2 Characterization Data for Alkenes S3–S5 References S5 NMR Spectra S6–S31 Instrumentation and Chemicals NMR spectra were recorded on a JEOL ECX-400, operating at 400 MHz for 1H NMR and 100.5 13 1 13 MHz for C NMR. Chemical shift values for H and C are referenced to Me4Si and the residual solvent resonances, respectively. Mass spectra were obtained with Thermo Fisher Scientific Exactive, JEOL JMS-T100LP or JEOL JMS-700TZ at the Instrumental Analysis Division, Equipment Management Center, Creative Research Institution, Hokkaido University. TLC analyses were performed on commercial glass plates bearing 0.25-mm layer of Merck Silica gel 60F254. Silica gel (Kanto Chemical Co., Silica gel 60 N, spherical, neutral) was used for column chromatography. Materials were obtained from commercial suppliers or prepared according to standard procedure unless otherwise noted. CuCl was purchased from Aldrich Chemical Co., stored under nitrogen, and used as it is. NatOBu, octane and 6-dodecyne 1a were purchased from TCI Chemical Co., stored under nitrogen, and used as it is. Diphenylacetylene 1j was purchased from Wako Chemical Co., stored under nitrogen, and used as it is. 1,4-Dioxane was purchased from Kanto Chemical Co., distilled from sodium/benzophenone and stored over 4Å molecular sieves under nitrogen.
    [Show full text]
  • The Synthesis of a Polydiacetylene to Create a Novel Sensory Material
    SELDE, KRISTEN A., M.S. The Synthesis of a Polydiacetylene to Create a Novel Sensory Material. (2007) Directed by Dr. Darrell Spells. 47pp. Sensory materials that respond to chemical and mechanical stimuli are under development in many laboratories. There are many significant uses of polydiacetylene compounds as sensory material. They have been applied to drug delivery, drug design, biomolecule development, cosmetics, and national security. In this study, experiments were carried out toward the development of a novel sensory material based on the established synthetic research on polydiacetylene compounds. Synthetic routes toward sensory materials with different head groups, different carbon chains lengths, and the incorporation of molecular imprints were explored. Diacetylene moieties, which can be used for polymer vesicle formation, were prepared by two main routes. In one route, 1-iodo-1-octyne and 1-iodo-1-dodecyne were prepared as starting materials for the synthesis of two diacetylene compounds (Diacetylene I and Diacetylene II). In the other route, a mesityl alkyne was used to prepare 5-iodo-1-pentyne, which was then used to prepare a triethylamino alkyne. This in turn was used to synthesize a diacetylene (Diacetylene III). Although each diacetylene product was formed, purification by column chromatography was found to be difficult. Experiments in vesicle formation, with and without molecular imprints, were also carried out using commercially available diacetylenes . THE SYNTHESIS OF A POLYDIACETYLENE TO CREATE A NOVEL SENSORY
    [Show full text]
  • Synthesis and Consecutive Reactions of Α-Azido Ketones: a Review
    Molecules 2015, 20, 14699-14745; doi:10.3390/molecules200814699 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Synthesis and Consecutive Reactions of α-Azido Ketones: A Review Sadia Faiz 1,†, Ameer Fawad Zahoor 1,*, Nasir Rasool 1,†, Muhammad Yousaf 1,†, Asim Mansha 1,†, Muhammad Zia-Ul-Haq 2,† and Hawa Z. E. Jaafar 3,* 1 Department of Chemistry, Government College University Faisalabad, Faisalabad-38000, Pakistan, E-Mails: [email protected] (S.F.); [email protected] (N.R.); [email protected] (M.Y.); [email protected] (A.M.) 2 Office of Research, Innovation and Commercialization, Lahore College for Women University, Lahore-54600, Pakistan; E-Mail: [email protected] 3 Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang-43400, Selangor, Malaysia † These authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: [email protected] (A.F.Z.); [email protected] (H.Z.E.J.); Tel.: +92-333-6729186 (A.F.Z.); Fax: +92-41-9201032 (A.F.Z.). Academic Editors: Richard A. Bunce, Philippe Belmont and Wim Dehaen Received: 20 April 2015 / Accepted: 3 June 2015 / Published: 13 August 2015 Abstract: This review paper covers the major synthetic approaches attempted towards the synthesis of α-azido ketones, as well as the synthetic applications/consecutive reactions of α-azido ketones. Keywords: α-azido ketones; synthetic applications; heterocycles; click reactions; drugs; azides 1. Introduction α-Azido ketones are very versatile and valuable synthetic intermediates, known for their wide variety of applications, such as in amine, imine, oxazole, pyrazole, triazole, pyrimidine, pyrazine, and amide alkaloid formation, etc.
    [Show full text]
  • Topologically Designed Cylindrical and Spherical Building
    TOPOLOGICALLY DESIGNED CYLINDRICAL AND SPHERICAL BUILDING BLOCKS TO CONSTRUCT MODULAR-ASSEMBLED STRUCTURES IN GIANT SHAPE-AMPHPHILES A Dissertation Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Jing Jiang May 2018 TOPOLOGICALLY DESIGNED CYLINDRICAL AND SPHERICAL BUILDING BLOCKS TO CONSTRUCT MODULAR-ASSEMBLED STRUCTURES IN GIANT SHAPE-AMPHPHILES Jing Jiang Dissertation Approved: Accepted: Advisor Department Chair Dr. Stephen Z. D. Cheng Dr. Coleen Pugh Committee Chair Dean of the College Dr. Toshikazu Miyoshi Dr. Eric J. Amis Committee Member Dean of the Graduate School Dr. Tianbo Liu Dr. Chand K. Midha Committee Member Date Dr. Yu Zhu Committee Member Dr. Chrys Wesdemiotis ii ABSTRACT Giant shape amphiphiles with isobutyl polyhedral oligomeric silsesquioxane (BPOSS) cages as the periphery at two discotic trisubstituted derivative of benzene cores were specifically designed and synthesized. Depending upon the number of BPOSS cages, these molecules first assembled into either cylindrical or spherical units via π-π interactions among the core unites. The packing of the molecules is mandated by the steric hindrance of the BPOSS cages at the periphery with hydrogen bonding interactions. If the space-packing is allowed, the cylindrical building block can form. Otherwise, the cylindrical building block will be forced to interrupt periodically and to form spherical building blocks. These units can further modular assemble into supramolecular structures. The cylindrical units form columnar structures with both hexagonal and rectangular packing, while the spherical units construct a Frank-Kasper A15 phase, similar to the metal alloy structures. In addition, based on the mechanism proposed by this work, five more giant shape amphiphiles with high steric hindrance on the periphery were synthesized, these giant shape amphiphiles successfully formed A15 phases with precisely size control, iii validating the reliability of this strategy.
    [Show full text]
  • Staudinger Ligation: a Peptide from a Thioester and Azide
    ORGANIC LETTERS 2000 Staudinger Ligation: A Peptide from a Vol. 2, No. 13 Thioester and Azide 1939-1941 Bradley L. Nilsson,† Laura L. Kiessling,†,‡ and Ronald T. Raines*,†,‡ Departments of Chemistry and Biochemistry, UniVersity of Wisconsin-Madison, Madison, Wisconsin 53706 [email protected] Received May 4, 2000 ABSTRACT The technique of native chemical ligation enables the total chemical synthesis of proteins. This method is limited, however, by an absolute requirement for a cysteine residue at the ligation juncture. Here, this restriction is overcome with a new chemical ligation method in which a phosphinobenzenethiol is used to link a thioester and azide. The product is an amide with no residual atoms. New methods are facilitating the total chemical synthesis of residue in one peptide attacks the carbon of a C-terminal proteins.1 In particular, Kent and others have developed an thioester in another peptide to produce, ultimately, an amide elegant means to stitch together two unprotected peptides in bond between the two peptides (Scheme 1). Recently, Muir aqueous solution.2 In this method, which is called “native chemical ligation”, the thiolate of an N-terminal cysteine Scheme 1 † Department of Chemistry. ‡ Department of Biochemistry. (1) For historical references, see: (a) Merrifield, R. B. Science 1984, 232, 341-347. (b) Kent, S. B. Annu. ReV. Biochem. 1988, 57, 957-989. (c) Kaiser, E. T. Acc. Chem. Res. 1989, 22,47-54. (2) Dawson, P. E.; Muir, T. W.; Clark-Lewis, I.; Kent, S. B. Science 1994, 266, 776-779. For important precedents, see: (a) Wieland, T.; Bokelmann, E.; Bauer, L.; Lang, H.
    [Show full text]
  • Development of a Solid-Supported Glaser-Hay Reaction and Utilization in Conjunction with Unnatural Amino Acids
    W&M ScholarWorks Dissertations, Theses, and Masters Projects Theses, Dissertations, & Master Projects 2015 Development of a Solid-Supported Glaser-Hay Reaction and Utilization in Conjunction with Unnatural Amino Acids Jessica S. Lampkowski College of William & Mary - Arts & Sciences Follow this and additional works at: https://scholarworks.wm.edu/etd Part of the Organic Chemistry Commons Recommended Citation Lampkowski, Jessica S., "Development of a Solid-Supported Glaser-Hay Reaction and Utilization in Conjunction with Unnatural Amino Acids" (2015). Dissertations, Theses, and Masters Projects. Paper 1539626985. https://dx.doi.org/doi:10.21220/s2-r9jh-9635 This Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Dissertations, Theses, and Masters Projects by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. Development of a Solid-Supported Glaser-Hay Reaction and Utilization in Conjunction with Unnatural Amino Acids Jessica Susan Lampkowski Ida, Michigan B.S. Chemistry, Siena Heights University, 2013 A Thesis presented to the Graduate Faculty of the College of William and Mary in Candidacy for the Degree of Master of Science Chemistry Department The College of William and Mary May, 2015 COMPLIANCE PAGE Research approved by Institutional Biosafety Committee Protocol number: BC-2012-09-13-8113-dyoung01 Date(s) of approval: This protocol will expire on 2015-11-02 APPROVAL PAGE This
    [Show full text]
  • Some Transition Metal Complexes of Trivalent Phosphorus Esters
    AN ABSTRACT OF THE THESIS OF HARRY VAUGHN STUDER for the MASTER OF SCIENCE (Name) (Degree) inCHEMISTRY (Inorganic) presented on ///( (Major) / (Date') Title: SOME TRANSITION METAL COMPLEXES OF TRIVALENT PHOSPHORUS ESTERS Redacted for Privacy Abstract approved: Dr. In T. Yoke r The ligands in the series EtnP(OEt)3_11, n = 0 - 3,all form pseudotetrahedral high-spin bis -complexes with cobalt (II) chloride. Magnetic, spectrophotometric, conductivity, and molecular weight data show that the phosphorus ester ligands (but not the phosphine) also form five-coordinate low-spin tris-complexes; these can be isolated with the phosphonite and phosphinite ligands, while the existence of the tris -phosphite is marginal.At cobalt (II) to phosphorus ester mole ratios of 1:2, a mixture of species is present in all cases.All are non-conducting in nitrobenzene. The ester complexes are much more susceptible to autoxidation than is the phosphine complex. Some Transition Metal Complexes of Trivalent Phosphorus Esters by Harry Vaughn Studer A THESIS submitted to Oregon State University in partial fulfillment of the requirements for the degree of Master of Science June 1972 APPROVED: Redacted for Privacy Profes of Chemi str y / in crge of major Redacted for Privacy Head of Department of Chemistry Redacted for Privacy Dean of Graduate School Date thesis is presented Typed by Donna Olson f arry Vatighn Studer ACKNOWLEDGEMENTS The author wishes to thank his research advisor, Dr. John T. Yoke, for his expert direction of this research, for his patience, and for the opportunity of learning through association with him. Acknowledgement is made to the donors of the Petroleum Re- search Fund, administered by the American Chemical Society, for the support of this work.
    [Show full text]
  • Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides
    Top Curr Chem (Z) (2016) 374:16 DOI 10.1007/s41061-016-0016-4 REVIEW Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides 1 1 Jan Dommerholt • Floris P. J. T. Rutjes • Floris L. van Delft2 Received: 24 November 2015 / Accepted: 17 February 2016 / Published online: 22 March 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract A nearly forgotten reaction discovered more than 60 years ago—the cycloaddition of a cyclic alkyne and an organic azide, leading to an aromatic triazole—enjoys a remarkable popularity. Originally discovered out of pure chemical curiosity, and dusted off early this century as an efficient and clean bio- conjugation tool, the usefulness of cyclooctyne–azide cycloaddition is now adopted in a wide range of fields of chemical science and beyond. Its ease of operation, broad solvent compatibility, 100 % atom efficiency, and the high stability of the resulting triazole product, just to name a few aspects, have catapulted this so-called strain-promoted azide–alkyne cycloaddition (SPAAC) right into the top-shelf of the toolbox of chemical biologists, material scientists, biotechnologists, medicinal chemists, and more. In this chapter, a brief historic overview of cycloalkynes is provided first, along with the main synthetic strategies to prepare cycloalkynes and their chemical reactivities. Core aspects of the strain-promoted reaction of cycloalkynes with azides are covered, as well as tools to achieve further reaction acceleration by means of modulation of cycloalkyne structure, nature of azide, and choice of solvent. Keywords Strain-promoted cycloaddition Á Cyclooctyne Á BCN Á DIBAC Á Azide This article is part of the Topical Collection ‘‘Cycloadditions in Bioorthogonal Chemistry’’; edited by Milan Vrabel, Thomas Carell & Floris P.
    [Show full text]
  • A. Discovery of Novel Reactivity Under the Sonogashira Reaction Conditions B. Synthesis of Functionalized Bodipys and BODIPY-Sug
    A. Discovery of novel reactivity under the Sonogashira reaction conditions B. Synthesis of functionalized BODIPYs and BODIPY-sugar conjugates Ravi Shekar Yalagala, M.Phil Department of Chemistry Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Faculty of Mathematics and Science, Brock University St. Catharines, Ontario © 2016 ABSTRACT A. During our attempts to synthesize substituted enediynes, coupling reactions between terminal alkynes and 1,2-cis-dihaloalkenes under the Sonogashira reaction conditions failed to give the corresponding substituted enediynes. Under these conditions, terminal alkynes underwent self-trimerization or tetramerization. In an alternative approach to access substituted enediynes, treatment of alkynes with trisubstituted (Z)- bromoalkenyl-pinacolboronates under Sonogashira coupling conditions was found to give 1,2,4,6-tetrasubstituted benzenes instead of Sonogashira coupled product. The reaction conditions and substrate scopes for these two new reactions were investigated. B. BODIPY core was functionalized with various functional groups such as nitromethyl, nitro, hydroxymethyl, carboxaldehyde by treating 4,4-difluoro-1,3,5,7,8- pentamethyl-2,6-diethyl-4-bora-3a,4a-diaza-s-indacene with copper (II) nitrate trihydrate under different conditions. Further, BODIPY derivatives with alkyne and azido functional groups were synthesized and conjugated to various glycosides by the Click reaction under the microwave conditions. One of the BODIPY–glycan conjugate was found to form liposome upon rehydration. The photochemical properties of BODIPY in these liposomes were characterized by fluorescent confocal microscopy. ii ACKNOWLEDGEMENTS I am extremely grateful to a number of people. Without their help, this document would have never been completed. First and foremost, I would like to thank my supervisor and mentor Professor Tony Yan for his guidance and supervision to make the thesis possible.
    [Show full text]