DOCSLIB.ORG

PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance Graduate School ETD Form 9 (Revised 12/07) PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance This is to certify that the thesis/dissertation prepared By Garrison L. Birch Entitled LIPIDOMIC PROFILING OF DICTYOSTELIUM DISCOIDEUM Master of Science For the degree of Is approved by the final examining committee: Robert E. Minto Chair Brenda J. Blacklock Michael J. McLeish To the best of my knowledge and as understood by the student in the Research Integrity and Copyright Disclaimer (Graduate School Form 20), this thesis/dissertation adheres to the provisions of Purdue University’s “Policy on Integrity in Research” and the use of copyrighted material. Approved by Major Professor(s): ____________________________________Robert E. Minto ____________________________________ Approved by: Martin J. O'Donnell 11/14/2011 Head of the Graduate Program Date Graduate School Form 20 (Revised 9/10) PURDUE UNIVERSITY GRADUATE SCHOOL Research Integrity and Copyright Disclaimer Title of Thesis/Dissertation: LIPIDOMIC PROFILING OF DICTYOSTELIUM DISCOIDEUM For the degree of MasterChoose ofyour Science degree I certify that in the preparation of this thesis, I have observed the provisions of Purdue University Executive Memorandum No. C-22, September 6, 1991, Policy on Integrity in Research.* Further, I certify that this work is free of plagiarism and all materials appearing in this thesis/dissertation have been properly quoted and attributed. I certify that all copyrighted material incorporated into this thesis/dissertation is in compliance with the United States’ copyright law and that I have received written permission from the copyright owners for my use of their work, which is beyond the scope of the law. I agree to indemnify and save harmless Purdue University from any and all claims that may be asserted or that may arise from any copyright violation. Garrison L. Birch ______________________________________ Printed Name and Signature of Candidate 11/14/2011 ______________________________________ Date (month/day/year) *Located at http://www.purdue.edu/policies/pages/teach_res_outreach/c_22.html LIPIDOMIC PROFILING OF DICTYOSTELIUM DISCOIDEUM A Thesis Submitted to the Faculty of Purdue University by Garrison L. Birch In Partial Fulfillment of the Requirements for the Degree of Master of Science December 2011 Purdue University Indianapolis, Indiana ii ACKNOWLEDGMENTS I am very grateful to the many people that encouraged and helped me along the journey of pursuing this degree. I would especially like to thank my advisor Dr. Brenda Blacklock for her wisdom and guidance. I also had the great pleasure of working with Dr. Robert Minto, who allowed me to collaborate on his research and gave me sound advice and support throughout my graduate career. I would also like to thank my committee members for their willingness to see me through this challenging process. Dr. Karl Dria and Mr. Cary Pritchard have been invaluable assets throughout my career. I would like to thank my lab co-workers, and particularly Michael Shepard, for their help, advice, and friendship. iii TABLE OF CONTENTS Page LIST OF TABLES ................................................................................................. v LIST OF FIGURES ...............................................................................................vi LIST OF ABBREVIATIONS .................................................................................. x ABSTRACT ........................................................................................................ xiii CHAPTER 1. INTRODUCTION ............................................................................ 1 1.1. Fatty acid elongation and Dictyostelium discoideum .................................. 1 1.2. Fatty acid biosynthesis and degradation .................................................... 6 1.2.1. Fatty Acid Biosynthesis ....................................................................... 7 1.2.2. Fatty Acid Degradation ...................................................................... 11 1.3. Sphingolipids ............................................................................................ 14 1.3.1. Sphingolipid Biosynthesis .................................................................. 17 CHAPTER 2. FATTY ACID PROFILING OF DICTYOSTELIUM DISCOIDEUM ..................................................................................................... 22 2.1. Introduction .............................................................................................. 22 2.2. Methods and materials ............................................................................. 23 2.2.1. Maintenance and growth of Dictyostelium discoideum ...................... 24 2.2.2. Preparation and Analysis of Derivatives ............................................ 24 2.3. Results and discussion ............................................................................ 26 2.3.1. Synthesis of authentic fatty acid standards ....................................... 26 2.3.2. The fatty acid profile of D. discoideum ............................................... 31 CHAPTER 3. FATTY ACID METABOLISM IN DICTYOSTELIUM DISCOIDEUM ..................................................................................................... 41 3.1. Introduction .............................................................................................. 41 3.2. Methods and materials ............................................................................. 43 3.2.1. Calculation of incorporation levels ..................................................... 43 3.2.2. Statistical analysis ............................................................................. 45 3.3. Results and discussion ............................................................................ 46 3.3.1. Synthesis of deuterium-labeled fatty acids ........................................ 46 3.3.2. In vivo feeding studies ....................................................................... 52 iv Page CHAPTER 4. SPHINGOLIPID CHARACTERIZATION IN DICTYOSTELIUM DISCOIDEUM ..................................................................................................... 74 4.1. Introduction .............................................................................................. 74 4.2. Methods and materials ............................................................................. 74 4.2.1. Culturing of D. discoideum and S. cerevisiae .................................... 75 4.2.2. Ba(OH)2 hydrolysis ............................................................................ 75 4.2.3. Dinitrophenyl derivatization of LCBs .................................................. 76 4.2.4. Total lipid extraction ........................................................................... 76 4.2.5. Mild alkaline hydrolysis ...................................................................... 77 4.2.6. Lithiation of sphingolipids .................................................................. 77 4.2.7. LC-MS analysis of lipids .................................................................... 78 4.3. Results and discussion ............................................................................ 82 4.3.1. Identification of sphingolipid long chain bases in D. discoideum ....... 82 4.3.2. Isolation of sphingolipids for characterization .................................... 93 4.3.3. Sphingolipid characterization for D. discoideum ................................ 98 4.3.4. Closing Remarks ............................................................................. 113 CHAPTER 5. EXPERIMENTAL DETAILS OF THE SYNTHESIS OF FATTY ACIDS .................................................................................................. 115 5.1. General experimental information .......................................................... 115 5.2. Synthetic standards for characterization of fatty acid profile .................. 116 5.2.1. Synthesis of 18:2 5,9 (35) ................................................................. 116 5.3. Production of 2H-labeled fatty acids for in vivo studies........................... 122 5.3.1. Synthesis of stearic acid-17,17,18,18,18-d5 (49) ............................. 123 5.3.2. Synthesis of stearic acid-3,3,4,4-d4 (55) .......................................... 127 5.3.3. Synthesis of octadec-5-enoic acid-16,16,17,17,18,18,18-d7 (74) .... 131 5.3.4. Synthesis of octadec-11-enoic acid-16,16,17,17,18,18,18-d7 (81) .. 137 5.4. Synthesis of 2H-labeled fatty acid stereoisomers ................................... 140 REFERENCES ................................................................................................. 152 APPENDIX ....................................................................................................... 163 v LIST OF TABLES Table Page Table 1. Summary of alkylations and the resulting products. ............................. 29 Table 2. GC-MS retention time comparison of methyl ester and pyrrolidine- derivatized synthetic standards to the FAs found in D. discoideum ...... 32 Table 3. Optimizer defined conditions for MRM. ................................................. 80 Table 4. Three long chain bases quantified by MRM as free LCBs .................... 88 Table 5. The sphingolipids of D. discoideum .................................................... 114 vi LIST OF FIGURES Figure Page Figure 1. Relevant lipid structures; a monounsaturated C18 fatty acid, a phospholipid, and the sphingolipids
Load more

Recommended publications
  • The Total Synthesis of Securinine and Other Methodology Studies
    University of Windsor Scholarship at UWindsor Electronic Theses and Dissertations Theses, Dissertations, and Major Papers 2010 The total synthesis of securinine and other methodology studies Bhartesh Dhudshia University of Windsor Follow this and additional works at: https://scholar.uwindsor.ca/etd Recommended Citation Dhudshia, Bhartesh, "The total synthesis of securinine and other methodology studies" (2010). Electronic Theses and Dissertations. 8275. https://scholar.uwindsor.ca/etd/8275 This online database contains the full-text of PhD dissertations and Masters’ theses of University of Windsor students from 1954 forward. These documents are made available for personal study and research purposes only, in accordance with the Canadian Copyright Act and the Creative Commons license—CC BY-NC-ND (Attribution, Non-Commercial, No Derivative Works). Under this license, works must always be attributed to the copyright holder (original author), cannot be used for any commercial purposes, and may not be altered. Any other use would require the permission of the copyright holder. Students may inquire about withdrawing their dissertation and/or thesis from this database. For additional inquiries, please contact the repository administrator via email ([email protected]) or by telephone at 519-253-3000ext. 3208. The Total Synthesis of Securinine and Other Methodology Studies by Bhartesh Dhudshia A Dissertation Submitted to the Faculty of Graduate Studies through the Department of Chemistry and Biochemistry in Partial Fulfillment of the Requirements
    [Show full text]
  • Effects of Surface Oxygen-Containing Groups of the Flowerlike Carbon
    catalysts Article Effects of Surface Oxygen-Containing Groups of the Flowerlike Carbon Nanosheets on Palladium Dispersion, Catalytic Activity and Stability in Hydrogenolytic Debenzylation of Tetraacetyldibenzylhexaazaisowurtzitane Yun Chen 1, Xinlei Ding 2, Wenge Qiu 2,* , Jianwei Song 3, Junping Nan 2, Guangmei Bai 2 and Siping Pang 1 1 School of Materials Science & Technology, Beijing Institute of Technology, Beijing 100081, China; [email protected] (Y.C.); [email protected] (S.P.) 2 Beijing Key Laboratory for Green Catalysis and Separation, College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100124, China; [email protected] (X.D.); [email protected] (J.N.); [email protected] (G.B.) 3 Qing Yang Chemical Industry Corporation, Liaoyang 111001, China; [email protected] * Correspondence: [email protected]; Tel.: +86-10-13521382103 Abstract: The influence of the surface chemical properties of the carbon support on the Pd dispersion, activity and stability of Pd(OH)2/C catalyst for the hydrogenolytic debenzylation of tetraacetyldiben- zylhexaazaisowurtzitane (TADB) was studied in detail. The flowerlike nanosheet carbon material (NSC) was chosen as the pristine support, meanwhile chemical oxidation with nitric acid and physical Citation: Chen, Y.; Ding, X.; Qiu, W.; calcination at 600 ◦C treatments were used to modify its surface properties, which were denoted as Song, J.; Nan, J.; Bai, G.; Pang, S. NSCox-2 (treated with 20 wt% HNO3) and NSC-600, respectively. The three carbon
    [Show full text]
  • Ammonium Formate Catalytic Transfer Hydrogenation:A Convenient Method for Removal of Halogenated Benzyloxycarbonyl and Benzyl Protecting Groups in Peptide Synthesis
    Indian Journal of Chemistry Vol. 39B, July 2000, pp. 504- 508 Ammonium formate catalytic transfer hydrogenation:A convenient method for removal of halogenated benzyloxycarbonyl and benzyl protecting groups in peptide synthesis D Channe G o wda·, B R ajesh & Shankare Gowd a Department of Studies in Chemistry, Uni versit y of Mysore, Manasagangotri , Mysore 570006, India Received 10 August ! 998; accepted (revised) 28 January 2000 A new appli cati on of ammonium fo rmate catalyti c transfer hydrogenolysis, in the presence of pall adised carbon, for removal of 2-chl orobenzyloxycarbony l (2-ClZ), 2,6-di chl orobenzyl (2,6-C 12Bzl), bro mobenzylo xycarbonyl (B rZ) and phenacyl ester (OPa) from amino acids, pepti des and hi gh molecul ar weight polymers is reported. Rapid and selecti ve removal of protecting groups un­ ti on and subsequent W:-branching were enhanced by der moderate, neutral and ambient conditions is often removal of the Boc group during each cycle by treat­ a necessary step in the a, rea of the peptide chemistry. ment for I hr with 50% TFA-CH2Ch when the Z A number of reagents have been developed for this group was used for N £-protection of lysine. purpose. The utility of ammonium formate in the Subsequently these problems were solved by em­ presence of I 0% palladium on carbon as reducin g pl oying more acid sta(?le 2-chlorobenzyloxycarbonyl agent for vari ous functi onal groups has been reviewed (2-CIZ) 11 group for W:-protection of lys in e and 2,6- 12 by Ram and Ehrenkanfer in 198i.
    [Show full text]
  • Heterogeneous Catalytic Hydrogenation
    •Platinum Metals Rev., 2012, 56, (4), 236–241• Heterogeneous Catalytic Hydrogenation Platinum group metals as hydrogenation catalysts in a two-day course http://dx.doi.org/10.1595/147106712X654187 http://www.platinummetalsreview.com/ Reviewed by Fabrizio Nerozzi Introduction Johnson Matthey, Catalysis and Chiral Technologies, Heterogeneous catalytic hydrogenations are important Orchard Road, Royston, Hertfordshire SG8 5HE, UK reactions that fi nd wide industrial application in Email: [email protected] the production of pharmaceuticals, agrochemicals, fi ne chemicals, fl avours, fragrances and dietary supplements. The reactions are generally highly selective and easy to work up, the catalyst can often be recovered and recycled, and the processes are atom effi cient. It is therefore no surprise that somewhere between 10–20% of the reactions used to produce chemicals today are catalytic hydrogenations. Despite the importance of the technique, and mainly because of its multidisciplinary nature, development chemists and engineers have a hard time fi nding training on this highly specialised subject. Scientifi c Update has fi lled this gap with a training course run for the fi rst time on the 16th and 17th of April 2012, in Brussels, Belgium (1). Attended by 35 scientists from 10 European countries and the USA, representing 27 chemical companies and research institutions, the course was an extensive scientifi c overview of heterogeneous catalytic hydrogenation, but also touched on engineering, safety and economic topics. The tutor was Felix Roessler, a catalysis expert who during his long career has worked at Roche and DSM, was honoured twice with the Sandmeyer Award granted by the Swiss Chemical Society (2), has authored 18 publications or monographs and holds 4 patents.
    [Show full text]
  • Zaed, Ahmed Mohamed Faraj (2012) New Tandem Reactions for the Synthesis of Nitrogen Containing Natural Products. Phd Thesis
    Zaed, Ahmed Mohamed Faraj (2012) New tandem reactions for the synthesis of nitrogen containing natural products. PhD thesis. http://theses.gla.ac.uk/3927/ Copyright and moral rights for this thesis are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Glasgow Theses Service http://theses.gla.ac.uk/ [email protected] New Tandem Reactions for the Synthesis of Nitrogen Containing Natural Products Ahmed M. Zaed (M. Sci) A thesis submitted in part fulfilment of the requirements of the degree of Doctor of Philosophy. School of Chemistry College of Science & Engineering University of Glasgow Glasgow G12 8QQ April 2012 2 Abstract During the course of the studies outlined in this thesis, a new approach for the synthesis of the tropane alkaloid, (±)-physoperuvine has been developed using a highly efficient one- pot tandem process which involved the Overman rearrangement and a ring closing metathesis reaction. An asymmetric one-pot tandem process has also been employed for the synthesis of the natural product, (+)-physoperuvine. This methodology was also applied to the generation of a late-stage intermediate that could be used in the synthesis of carbocyclic nucleosides, such as noraristeromycin.
    [Show full text]
  • Conversion of D-Xylose to Carboxylic Acids in a Capillary Fluidized Bed
    UNIVERSITÉ DE MONTRÉAL CONVERSION OF D-XYLOSE TO CARBOXYLIC ACIDS IN A CAPILLARY FLUIDIZED BED TOURAJ GHAZNAVI DÉPARTEMENT DE GÉNIE CHIMIQUE ÉCOLE POLYTECHNIQUE DE MONTRÉAL MÉMOIRE PRÉSENTÉ EN VUE DE L’OBTENTION DU DIPLÔME DE MAÎTRISE ÈS SCIENCES APPLIQUÉES (GÉNIE CHIMIQUE) JUIN 2014 © Touraj Ghaznavi, 2014. UNIVERSITÉ DE MONTRÉAL ÉCOLE POLYTECHNIQUE DE MONTRÉAL Ce mémoire intitulé: CONVERSION OF D-XYLOSE TO CARBOXYLIC ACIDS IN A CAPILLARY FLUIDIZED BED présenté par : GHAZNAVI Touraj en vue de l’obtention du diplôme de : Maîtrise ès sciences appliquées a été dûment accepté par le jury d’examen constitué de : M. CICOIRA Fabio, Ph.D., président M. PATIENCE Gregory S., Ph.D., membre et directeur de recherche M. LEGROS Robert, Ph.D., membre iii DEDICATION To my father iv ACKNOWLEDGMENTS It was a privilege to work with Professor Gregory Patience, he provided me with an opportunity to capitalize on my intrinsic resources to fulfill my ambitions and wishes. I appreciate his continuous support during my program. During the completion of this research I had an excellent opportunity to work with Dr. Cristian Neagoe, and I learnt many things from him that I will use in all stages of my life. He is someone whom I will never forget. Thanks to Prof. Fabio Cicoira and Prof. Robert Legros for taking part in my thesis committee. Dr. Mahdi Jazayeri has helped me a lot over the years, and I consider him a great friend. The support of our research group was also crucial to this work, so I’d to thank all of them. I would like to thank Mr.
    [Show full text]
  • Palladium on Carbon
    Palladium on Carbon [7440-05-3] · Pd · Palladium on Carbon · (MW 106.42) (catalyst for hydrogenation of alkenes, alkynes, ketones, nitriles, imines, azides, nitro groups, benzenoid and heterocyclic aromatics; used for hydrogenolysis of cyclopropanes, benzyl derivatives, epoxides, hydrazines, and halides; used to dehydrogenate aromatics and deformylate aldehydes) Solubility: insol all organic solvents and aqueous acidic media. Form Supplied in: black powder or pellets containing 0.5-30 wt % of Pd (typically 5 wt %); can be either dry or moist (50 wt % of H2O). Analysis of Reagent Purity: atomic absorption. Handling, Storage, and Precautions: can be stored safely in a closed container under air but away from solvents and potential poisons such as sulfur- and phosphorus-containing compounds. Pyrophoric in the presence of solvents. General precautions for handling hydrogenation catalysts should be followed. The catalyst must be suspended in the organic solvent under an atmosphere of N2. During filtration the filter cake must not be allowed to go dry. If a filter aid is necessary, a cellulose-based material should be used if catalyst recovery is desired. Hydrogenation and Hydrogenolysis: Carbon-Carbon Bonds. The use of Pd/C for the selective reduction of alkynes to alkenes is generally not satisfactory, but a few examples have been reported. For example, the Pd/C-catalyzed reduction of 3,6-dimethyl-4-octyne-3,6- 1 diol gave the enediol in 98% yield after absorption of 1 mol of H2. Further reduction gave the diol in 99% yield. Pd on other supports, such as Pd/CaCO3 and Pd/BaCO3, are much more effective for this conversion.
    [Show full text]
  • Method Development for the Stereoselective Synthesis of Medium-Sized Cyclic Ethers and Application to Natural Product Synthesis: Part I
    Method Development for the Stereoselective Synthesis of Medium-Sized Cyclic Ethers and Application to Natural Product Synthesis: Part I. Organocatalytic Oxa-Conjugate Addition for α,α´-trans-Oxepanes Part II. Gold(I)-Catalyzed Alkoxylation for α,α´-cis - Oxocenes Part III. Studies toward the Synthesis of (+)-Intricenyne by Megan L. Lanier Department of Chemistry Duke University Date:_______________________ Approved: ___________________________ Jiyong Hong, Supervisor ___________________________ Ross A. Widenhoefer ___________________________ Qiu Wang ___________________________ Katherine J. Franz Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry in the Graduate School of Duke University 2015 ABSTRACT Method Development for the Stereoselective Synthesis of Medium-Sized Cyclic Ethers and Application to Natural Product Synthesis: Part I. Organocatalytic Oxa-Conjugate Addition for α,α´-trans-Oxepanes Part II. Gold(I)-Catalyzed Alkoxylation for α,α´-cis - Oxocenes Part III. Studies toward the Synthesis of (+)-Intricenyne by Megan L. Lanier Department of Chemistry Duke University Date:_______________________ Approved: ___________________________ Jiyong Hong, Supervisor ___________________________ Ross A. Widenhoefer ___________________________ Qiu Wang ___________________________ Katherine J. Franz An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry in the Graduate School of Duke University 2015 Copyright by Megan L. Lanier 2015 Abstract Medium-sized cyclic ethers are challenging synthetic targets due to enthalpic and entropic barriers. Methods for the stereoselective synthesis of α,α΄-disubstituted medium- sized cyclic ethers began to appear with the discovery of naturally-occurring, ladder- shaped polycyclic ethers, such as brevetoxin B, and monocyclic ethers, such as (+)- laurencin.
    [Show full text]
  • Carbon Bonds Formation
    Accepted Article Title: Carbon-Derived Supports for Palladium Nanoparticles as Catalysts for Carbon-Carbon Bonds Formation Authors: Carmen Nájera, Mohammad Gholinejad, and Zhwan Naghshbandi This manuscript has been accepted after peer review and appears as an Accepted Article online prior to editing, proofing, and formal publication of the final Version of Record (VoR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article. To be cited as: ChemCatChem 10.1002/cctc.201802101 Link to VoR: http://dx.doi.org/10.1002/cctc.201802101 A Journal of www.chemcatchem.org ChemCatChem 10.1002/cctc.201802101 FULL PAPER Carbon-Derived Supports for Palladium Nanoparticles as Catalysts for Carbon-Carbon Bonds Formation Mohammad Gholinejad,*[a,b] Zhwan Naghshbandi,[a] Carmen Nájera,*[c] Abstract: The review considers the variety allotropes of carbon to be of palladium and its toxic property, separation, recovery and used as supports for palladium and investigation of the resulting reutilization of the palladium catalyst represents a crucial factor catalysts for carbon-carbon forming reactions with focus on the effect for the sustainable development of C-C bond forming reactions. of the solvent, base and catalyst loading in the catalyst recovery. In recent years, many heterogeneous palladium catalysts Specially, carbon nanotubes, C60 and graphene allowed the covalent supported on various solids such as polymers, magnetic functionalization with different ligands for palladium facilitating a lower nanoparticles, silica, polysaccharides etc.
    [Show full text]
  • Development of New Novel Bacterial Topoisomerase Inhibitors As Promising Antibiotics with a 5-Amino-1,3-Dioxane Linker Moiety DI
    Development of New Novel Bacterial Topoisomerase Inhibitors as Promising Antibiotics with a 5-Amino-1,3-dioxane Linker Moiety DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Linsen Li Graduate Program in Pharmaceutical Sciences The Ohio State University 2019 Dissertation Committee: Mark J Mitton-Fry, Ph.D., Advisor Karl A Werbovetz, Ph.D. Mireia Guerau-de-Arellano, Ph.D. James R Fuchs, Ph.D. Copyright by Linsen Li 2019 Abstract Multidrug-resistant bacteria (MDR) have become one of the greatest threats to human beings. Regardless of the mechanism of action involved, resistance has eventually developed after the clinical use of each class of antibiotics. Thus, new antibiotic classes with unprecedented mechanisms of action are in urgent demand. With a distinct mechanism of action, Novel Bacterial Topoisomerase Inhibitors (NBTIs) represent a promising new class of antibiotics. The recent development of NBTIs has been encouraging. Several NBTIs have processed to clinical trials, and one NBTI (Gepotidacin) has successfully completed Phase 2 clinical trials. However, the cardiac toxicity from the inhibition of hERG K+ channels is one of the major challenges in the discovery of NBTIs. In this work, a 5-amino-1,3-dioxane linker moiety was incorporated in new NBTIs to decrease hERG inhibition, which was demonstrated by comparison with several structure- matched pairs with other linker moieties. A variety of NBTIs with a 5-amino-1,3-dioxane linker have been synthesized and evaluated. Many of these newly synthesized NBTIs showed potent antibacterial activity, covering methicillin-resistant Staphylococcus aureus (MRSA) and fluoroquinolone-resistant strains.
    [Show full text]
  • Research.Pdf
    FORMAL TOTAL SYNTHESIS OF PSEUDOPTEROXAZOLE. PROGRESS TOWARD TOTAL SYNTHESIS OF HAMIGERAN B. _______________________________________ A Dissertation presented to the Faculty of the Graduate School at the University of Missouri-Columbia _______________________________________________________ In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy _____________________________________________________ by ZHENGXIN CAI Dr. Michael Harmata, Dissertation Supervisor JULY 2011 © Copyright by Zhengxin Cai 2011 All Rights Reserved The undersigned, appointed by the dean of the Graduate School, have examined the dissertation entitled FORMAL SYNTHESIS OF PSEUDOPTEROXAZOLE. PROGRESS TOWARD TOTAL SYNTHESIS OF HAMIGERAN B presented by Zhengxi Cai, a candidate for the degree of doctor of philosophy, and hereby certify that, in their opinion, it is worthy of acceptance. Professor Michael Harmata Professor Susan Z. Lever Professor Timothy E. Glass Professor Paul R. Sharp Professor Peter A. Tipton Dedicated to my daughter Caroline, my wife Jing and my parents. ACKNOWLEDGEMENTS I would like to thank my supervisor, Professor Michael Harmata, for his inspiration and pedagogics. My research and dissertation could not be done without his encouragement and strong support. I also would like to thank all of my committee members: Professor Susan Lever, Professor Timothy Glass, Professor Paul Sharp and Professor Peter Tipton, for their advice and comments. Thanks Carissa and Eric for detailed proofreading of my first craft. Thanks Jing for scanning NMR, IR, etc. I would like to acknowledge Dr. Wei Wycoff, for teaching and helping me on the NMR techniques and Dr. Charles Barnes for his X-ray crystallography support. Thanks Dr. Nathan for mass spectrum assistance. Thanks all of chemistry department staff, especially, Jerry Brightwell for his assistance and great patience.
    [Show full text]
  • Synthetic and Theoretical Studies for Cyclization Reactions to Form C-C and C-N Bonds
    The University of Southern Mississippi The Aquila Digital Community Dissertations Summer 8-1-2018 Synthetic and Theoretical Studies for Cyclization Reactions to Form C-C and C-N Bonds Nicholas Jentsch University of Southern Mississippi Follow this and additional works at: https://aquila.usm.edu/dissertations Part of the Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons, and the Physical Chemistry Commons Recommended Citation Jentsch, Nicholas, "Synthetic and Theoretical Studies for Cyclization Reactions to Form C-C and C-N Bonds" (2018). Dissertations. 1542. https://aquila.usm.edu/dissertations/1542 This Dissertation is brought to you for free and open access by The Aquila Digital Community. It has been accepted for inclusion in Dissertations by an authorized administrator of The Aquila Digital Community. For more information, please contact [email protected]. SYNTHETIC AND THEORETICAL STUDIES FOR CYCLIZATION REACTIONS TO FORM C-C AND C-N BONDS by Nicholas Jentsch A Dissertation Submitted to the Graduate School, the College of Science and Technology and the Department of Chemistry and Biochemistry at The University of Southern Mississippi in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Approved by: Dr. Matthew Donahue, Committee Chair Dr. Julie Pigza Dr. Douglas Masterson Dr. Vijay Rangachari Dr. Ras Pandey ____________________ ____________________ ____________________ Dr. Matthew Donahue Dr. Vijay Rangachari Dr. Karen S. Coats Committee Chair Department Chair Dean of the Graduate School August 2018 COPYRIGHT BY Nicholas Jentsch 2018 Published by the Graduate School ABSTRACT Natural product total synthesis provides an alternative method for obtaining medicinally relevant compounds in a more efficient process with higher yields than what nature can provide.
    [Show full text]