DOCSLIB.ORG

Studies on the Prebiotic Origin of 2-Deoxy-D-Ribose

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Studies on the Prebiotic Origin of 2-Deoxy-D-Ribose Studies on the Prebiotic Origin of 2-Deoxy-D-ribose Andrew Mark Steer Doctor of Philosophy University of York Chemistry August 2017 Abstract DNA is an important biological structure necessary for cell proliferation. The origins of cell- like structures and the building blocks of DNA are therefore also of great concern. As of yet the prebiotic origin of 2-deoxy-D-ribose, the sugar of DNA, has no satisfactory explanation. This research attempts to provide a possible explanation to the chemical origin of 2-deoxy- D-ribose via an aldol reaction between acetaldehyde 1 and D-glyceraldehyde D-2 (Error! Reference source not found.). The sugar mixture is trapped with N,N-diphenylhydrazine 3 for ease of purification and characterisation. The reaction is promoted by amino acids, amino esters and amino nitriles consistently giving selectivities in favour of 2-deoxy-D- ribose. This is the first example of an amino nitrile promoted reaction. Potential prebiotic synthesis of 2-deoxy-D-ribose and subsequent trapping with N,N-diphenyl hydrazine 3. The research is developed further by exploring the formation of 2-deoxy-D-ribose in a “protocell” environment – a primitive cell. Here we suggest that primitive cells may have been simple hydrogel systems. A discussion of the characterisation and catalytic ability of small peptide-based supramolecular structures is included. ii Contents Abstract ............................................................................................................................ ii Contents .......................................................................................................................... iii List of Figures .................................................................................................................. v List of Schemes ............................................................................................................ viii List of Tables ................................................................................................................... x Acknowledgements ....................................................................................................... xii Declaration .................................................................................................................... xiii 1. Introduction ............................................................................................................... 1 1.1. The Origin of Life and the RNA World hypothesis ................................................ 1 1.2. The Origin of Sugars............................................................................................ 6 1.3. Prebiotic Relevance of Amino Acids .................................................................... 8 1.4. Amino acids as catalysts in aldol reactions ........................................................ 15 1.5. Organocatalysis in water ................................................................................... 20 1.6. Peptides in organocatalysis ............................................................................... 30 1.7. Amino acid-catalysed sugar chemistry in a prebiotic scenario ........................... 34 1.8. Amplification of a Small Enantiomeric Excess.................................................... 43 1.9. Approaches to 2-Deoxyribose ............................................................................ 48 1.10. Conclusions and Research Objectives ........................................................... 51 2. A Prebiotic Route to 2-Deoxy-D-Ribose ................................................................ 53 2..1. Initial experimental design ................................................................................. 53 1. Synthesis of Standards and Catalysts ................................................................... 56 2. Results of the Initial reaction trials ......................................................................... 61 3. N, N-Diphenyl hydrazine trap ................................................................................ 67 4. Conclusion ............................................................................................................ 75 3. Amino nitriles – possible progenitors to amino acids ......................................... 76 3.1. Evidence for amino nitriles as prebiotic molecules ............................................. 76 3.2. Synthesis of amino nitriles ................................................................................. 79 3.3. Amino nitriles as potential catalysts ................................................................... 83 3.4. Prebiotic formation of glyceraldehyde ................................................................ 87 3.5. Racemic glyceraldehyde .................................................................................... 91 3.6. One pot synthesis of 2-deoxyribose ................................................................... 96 3.7. Conclusions ..................................................................................................... 103 4. Prebiotic Protocells .............................................................................................. 105 4.1. A Protocell Environment .................................................................................. 105 4.2. Proof of concept using agarose ....................................................................... 111 iii 4.3. Prebiotic protocells based on dipeptide amphiphile hydrogels ......................... 117 4.4. Conclusions ..................................................................................................... 130 5. Further investigations into hydrogel catalysis ................................................... 131 5.1. A tripeptide hydrogel candidate ....................................................................... 131 5.2. Supramolecular structures of a tripeptide amide .............................................. 137 5.3. Evidence of Micelle Aggregation ...................................................................... 140 5.4. Changing the amino acid sequence ................................................................. 147 5.5. Single amino amides for supramolecular catalysis ........................................... 149 5.6. Conclusions ..................................................................................................... 156 6. Experimental ......................................................................................................... 157 Abbreviations ............................................................................................................... 225 References ................................................................................................................... 228 iv List of Figures Figure 1.1. Central dogma of molecular biology. .................................................................. 1 Figure 1.2. The processes of transcription and translation that occur within a mammalian cell. ....................................................................................................................................... 2 Figure 1.3. Miller-Urey experimental set-up and amino acids synthesised. Reprinted with permission from J. Am .Chem. Soc., 1995, 77, 2351. Copyright 2017 American Chemical Society. ................................................................................................................................. 9 Figure 1.4. Five methyl-α-amino acids found in fragments of the Murchison meteorite. ...... 13 Figure 1.5. Proposed transition states leading to Si-facial attack in the L-histidine L-81 catalysed aldol reaction.67 ................................................................................................... 27 Figure 1.6. Catalyst 86 and relative transition state proposed by Pedatella et al.71 ............. 29 Figure 1.7. Proline derived catalyst 87 synthesised by Lipshutz and Ghorai.72 ................... 30 Figure 1.8. Conversion of amino nitriles to amino amides using pentose sugars and the resultant .............................................................................................................................. 46 Figure 2.1. DNA anti-parallelhelix and a magnified region of the primary structure of DNA showing deoxyribose, phosphate and a nucleic base. ......................................................... 53 Figure 2.2. Product and reagent hydrazone standards. ...................................................... 56 Figure 2.3. ESI mass spectrum for the 2-deoxyribose-forming reaction after 72 hours of trapping. The correct mass of trapped 2-deoxyribose 132 is present. ................................ 66 Figure 2.4. Trapped hydrazone standards and their yields using N,N-diphenyl hydrazine 144 after stirring for 1 hour in methanol and catalytic acetic acid. The crystal structure of 146 is also shown as 50 % ellipsoid. ............................................................................................. 69 Figure 2.5. 500 MHz 1H NMR spectrum of a mixture of hydrazones D-146 and D-147 in methanol d4. ........................................................................................................................ 70 Figure 2.6. 500 MHz 1H NMR spectrum of 2-deoxy-D-ribose hydrazone D-146 in methanol d4. ....................................................................................................................................... 71 Figure 2.7. 500 MHz 1H NMR spectrum of
Load more

Recommended publications
  • Studies Toward Synthesis of Polycyclic Polyprenylated Acylphloroglucinols
    University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2006 STUDIES TOWARD SYNTHESIS OF POLYCYCLIC POLYPRENYLATED ACYLPHLOROGLUCINOLS Roxana Ciochina University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Ciochina, Roxana, "STUDIES TOWARD SYNTHESIS OF POLYCYCLIC POLYPRENYLATED ACYLPHLOROGLUCINOLS" (2006). University of Kentucky Doctoral Dissertations. 291. https://uknowledge.uky.edu/gradschool_diss/291 This Dissertation is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Doctoral Dissertations by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF DISSERTATION Roxana Ciochina The Graduate School University of Kentucky 2006 STUDIES TOWARD SYNTHESIS OF POLYCYCLIC POLYPRENYLATED ACYLPHLOROGLUCINOLS ABSTRACT OF DISSERTATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Arts and Sciences at the University of Kentucky By Roxana Ciochina Lexington, KY Director: Dr. R. B. Grossman, Professor of Chemistry Lexington, KY 2006 ABSTRACT OF DISSERTATION STUDIES TOWARD SYNTHESIS OF POLYCYCLIC POLYPRENYLATED ACYLPHLOROGLUCINOLS Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of compounds that reveal intriguing biological activities and interesting and challenging chemical structures. These products are claimed to possess antioxidant, antiviral, and antimitotic properties. Increasing interest is related to their function in the CNS as modulators of neurotransmitters associated to neuronal damaging and depression. All these features make PPAPs targets for synthesis. We decided to focus our own initial efforts in this area on the type A PPAP, nemorosone because we thought that its fairly simple structure relative to other PPAPs would present fewer hurdles as we developed our methodology.
    [Show full text]
  • Xylose Fermentation to Ethanol by Schizosaccharomyces Pombe Clones with Xylose Isomerase Gene." Biotechnology Letters (8:4); Pp
    NREL!TP-421-4944 • UC Category: 246 • DE93000067 l I Xylose Fermenta to Ethanol: A R ew '.) i I, -- , ) )I' J. D. McMillan I ' J.( .!i �/ .6' ....� .T u�.•ls:l ., �-- • National Renewable Energy Laboratory II 'J 1617 Cole Boulevard Golden, Colorado 80401-3393 A Division of Midwest Research Institute Operated for the U.S. Department of Energy under Contract No. DE-AC02-83CH10093 Prepared under task no. BF223732 January 1993 NOTICE This report was prepared as an account of work sponsored by an agency of the United States government. Neither the United States government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, com­ pleteness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily con­ stitute or imply its endorsement, recommendation, or favoring by the United States government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States government or any agency thereof. Printed in the United States of America Available from: National Technical Information Service U.S. Department of Commerce 5285 Port Royal Road Springfield, VA22161 Price: Microfiche A01 Printed Copy A03 Codes are used for pricing all publications. The code is determined by the number of pages in the publication. Information pertaining to the pricing codes can be found in the current issue of the following publications which are generally available in most libraries: Energy Research Abstracts (ERA); Govern­ ment Reports Announcements and Index ( GRA and I); Scientific and Technical Abstract Reports(STAR); and publication NTIS-PR-360 available from NTIS at the above address.
    [Show full text]
  • United States Patent Office
    - 2,926,180 United States Patent Office Patented Feb. 23, 1960 2 cycloalkyl, etc. These substituents R and R' may also be substituted with various groupings such as carboxyl 2,926,180 groups, sulfo groups, halogen atoms, etc. Examples of CONDENSATION OF AROMATIC KETONES WITH compounds which are included within the scope of this CARBOHYDRATES AND RELATED MATER ALS 5 general formula are acetophenone, propiophenone, benzo Carl B. Linn, Riverside, Ill., assignor, by mesne assign phenone, acetomesitylene, phenylglyoxal, benzylaceto ments, to Universal Oil Products Company, Des phenone, dypnone, dibenzoylmethane, benzopinacolone, Plaines, Ill., a corporation of Delaware dimethylaminobenzophenone, acetonaphthalene, benzoyl No Drawing. Application June 18, 1957 naphthalene, acetonaphthacene, benzoylnaphthacene, ben 10 zil, benzilacetophenone, ortho-hydroxyacetophenone, para Serial No. 666,489 hydroxyacetophenone, ortho - hydroxy-para - methoxy 5 Claims. (C. 260-345.9) acetophenone, para-hydroxy-meta-methoxyacetophenone, zingerone, etc. This application is a continuation-in-part of my co Carbohydrates which are condensed with aromatic pending application Serial No. 401,068, filed December 5 ketones to form a compound selected from the group 29, 1953, now Patent No. 2,798,079. consisting of an acylaryl-desoxy-alditol and an acylaryl This invention relates to a process for interacting aro desoxy-ketitol include simple sugars, their desoxy- and matic ketones with carbohydrates and materials closely omega-carboxy derivatives, compound sugars or oligo related to carbohydrates. The process relates more par saccharides, and polysaccharides. ticularly to the condensation of simple sugars, their 20 Simple sugars include dioses, trioses, tetroses, pentoses, desoxy- and their omega-carboxy derivatives, compound hexoses, heptoses, octoses, nonoses, and decoses. Com sugars or oligosaccharides, and polysaccharides with aro pound sugars include disaccharides, trisaccharides, and matic ketones in the presence of a hydrogen fluoride tetrasaccharides.
    [Show full text]
  • 1. Nucleotides A. Pentose Sugars – 5-Carbon Sugar 1) Deoxyribose – in DNA 2) Ribose – in RNA B. Phosphate Group C. Nitroge
    1. Nucleotides a. Pentose sugars – 5-Carbon sugar 1) Deoxyribose – in DNA 2) Ribose – in RNA b. Phosphate group c. Nitrogenous bases 1) Purines a) Adenine b) Guanine 2) Pyrimidines a) Cytosine b) Thymine 2. Types of Nucleic Acids a. DNA 1) Locations 2) Functions b. RNA 1) Locations 2) Functions E. High Energy Biomolecules 1. Adenosine triphosphate a. Uses 1) Active transport 2) Movement 3) Biosynthesis reactions b. Regeneration 1) ADP + Pi + Energy → ATP 4. Classes of proteins a. Structural – ex. Collagen, keratin b. Transport – Hemoglobin, many β-globulins c. Contractile – Actin and Myosin of muscle tissue d. Regulatory - Hormones e. Immunologic - Antibodies f. Clotting – Thrombin and Fibrin g. Osmotic - Albumin h. Catalytic – Enzymes 1) Characteristics of enzymes • Proteins (most); ribonucleoproteins (few/ribozymes) • Act as organic catalysts • Lower the activation energy of reactions • Not changed by the reaction • Bind to their substrates o Lock-and-key model of enzyme activity o Induced-fit model • Highly specific • Named by adding -ase to substrate name; e.g., maltose/maltase • May require cofactors which may be: o Nonprotein metal ions such as copper, manganese, potassium, sodium o Small organic molecules known as coenzymes. The B vitamins like thiamine (B1) riboflavin (B2) and nicotinamide are precursors of coenzymes. • May require activation; e.g., pepsinogen pepsin in stomach chief cells 4. Factors Affecting Enzyme Action • pH o pepsin (stomach) @ pH = 2; trypsin (small int.) @ pH = 8 • Temperature o Denatured by high temp’s. • Enzyme inhibitors o Competitive inhibitors o Noncompetitive inhibitors • Effect of substrate concentration and reversible reactions and the Law of Mass D.
    [Show full text]
  • PENTOSE PHOSPHATE PATHWAY — Restricted for Students Enrolled in MCB102, UC Berkeley, Spring 2008 ONLY
    Metabolism Lecture 5 — PENTOSE PHOSPHATE PATHWAY — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY Bryan Krantz: University of California, Berkeley MCB 102, Spring 2008, Metabolism Lecture 5 Reading: Ch. 14 of Principles of Biochemistry, “Glycolysis, Gluconeogenesis, & Pentose Phosphate Pathway.” PENTOSE PHOSPHATE PATHWAY This pathway produces ribose from glucose, and it also generates 2 NADPH. Two Phases: [1] Oxidative Phase & [2] Non-oxidative Phase + + Glucose 6-Phosphate + 2 NADP + H2O Ribose 5-Phosphate + 2 NADPH + CO2 + 2H ● What are pentoses? Why do we need them? ◦ DNA & RNA ◦ Cofactors in enzymes ● Where do we get them? Diet and from glucose (and other sugars) via the Pentose Phosphate Pathway. ● Is the Pentose Phosphate Pathway just about making ribose sugars from glucose? (1) Important for biosynthetic pathways using NADPH, and (2) a high cytosolic reducing potential from NADPH is sometimes required to advert oxidative damage by radicals, e.g., ● - ● O2 and H—O Metabolism Lecture 5 — PENTOSE PHOSPHATE PATHWAY — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY Two Phases of the Pentose Pathway Metabolism Lecture 5 — PENTOSE PHOSPHATE PATHWAY — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY NADPH vs. NADH Metabolism Lecture 5 — PENTOSE PHOSPHATE PATHWAY — Restricted for students enrolled in MCB102, UC Berkeley, Spring 2008 ONLY Oxidative Phase: Glucose-6-P Ribose-5-P Glucose 6-phosphate dehydrogenase. First enzymatic step in oxidative phase, converting NADP+ to NADPH. Glucose 6-phosphate + NADP+ 6-Phosphoglucono-δ-lactone + NADPH + H+ Mechanism. Oxidation reaction of C1 position. Hydride transfer to the NADP+, forming a lactone, which is an intra-molecular ester.
    [Show full text]
  • Monosaccharide Disaccharide Oligosaccharide Polysaccharide Monosaccharide
    Carbohydrates Classification of Carbohydrates monosaccharide disaccharide oligosaccharide polysaccharide Monosaccharide is not cleaved to a simpler carbohydrate on hydrolysis glucose, for example, is a monosaccharide Disaccharide is cleaved to two monosaccharides on hydrolysis these two monosaccharides may be the same or different C12H22O11 + H2O C6H12O6 + C6H12O6 glucose sucrose (a monosaccharide) fructose (a disaccharide) (a monosaccharide) Higher Saccharides oligosaccharide: gives two or more monosaccharide units on hydrolysis is homogeneous—all molecules of a particular oligosaccharide are the same, including chain length polysaccharide: yields "many" monosaccharide units on hydrolysis mixtures of the same polysaccharide differing only in chain length Some Classes of Carbohydrates No. of carbons Aldose Ketose 4 Aldotetrose Ketotetrose 5 Aldopentose Ketopentose 6 Aldohexose Ketopentose 7 Aldoheptose Ketoheptose 8 Aldooctose Ketooctose Fischer Projections and D-L Notation Fischer Projections Fischer Projections Fischer Projections of Enantiomers Enantiomers of Glyceraldehyde CH O CH O H OH HO H D L CH2OH CH2OH (+)-Glyceraldehyde (–)-Glyceraldehyde The Aldotetroses An Aldotetrose 1 CH O 2 H OH 3 H OH D 4 CH2OH stereochemistry assigned on basis of whether configuration of highest-numbered stereogenic center is analogous to D or L-glyceraldehyde An Aldotetrose 1 CH O 2 H OH 3 H OH 4 CH2OH D-Erythrose The Four Aldotetroses CH O CH O H OH HO H D-Erythrose and L-erythrose are H OH HO H enantiomers CH2OH CH2OH D-Erythrose L-Erythrose The Four
    [Show full text]
  • Multi-Enzymatic Cascades in the Synthesis of Modified Nucleosides
    biomolecules Article Multi-Enzymatic Cascades in the Synthesis of Modified Nucleosides: Comparison of the Thermophilic and Mesophilic Pathways Ilja V. Fateev , Maria A. Kostromina, Yuliya A. Abramchik, Barbara Z. Eletskaya , Olga O. Mikheeva, Dmitry D. Lukoshin, Evgeniy A. Zayats , Maria Ya. Berzina, Elena V. Dorofeeva, Alexander S. Paramonov , Alexey L. Kayushin, Irina D. Konstantinova * and Roman S. Esipov Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16/10, 117997 GSP, B-437 Moscow, Russia; [email protected] (I.V.F.); [email protected] (M.A.K.); [email protected] (Y.A.A.); [email protected] (B.Z.E.); [email protected] (O.O.M.); [email protected] (D.D.L.); [email protected] (E.A.Z.); [email protected] (M.Y.B.); [email protected] (E.V.D.); [email protected] (A.S.P.); [email protected] (A.L.K.); [email protected] (R.S.E.) * Correspondence: [email protected]; Tel.: +7-905-791-1719 ! Abstract: A comparative study of the possibilities of using ribokinase phosphopentomutase ! nucleoside phosphorylase cascades in the synthesis of modified nucleosides was carried out. Citation: Fateev, I.V.; Kostromina, Recombinant phosphopentomutase from Thermus thermophilus HB27 was obtained for the first time: M.A.; Abramchik, Y.A.; Eletskaya, a strain producing a soluble form of the enzyme was created, and a method for its isolation and B.Z.; Mikheeva, O.O.; Lukoshin, D.D.; chromatographic purification was developed. It was shown that cascade syntheses of modified nu- Zayats, E.A.; Berzina, M.Y..; cleosides can be carried out both by the mesophilic and thermophilic routes from D-pentoses: ribose, Dorofeeva, E.V.; Paramonov, A.S.; 2-deoxyribose, arabinose, xylose, and 2-deoxy-2-fluoroarabinose.
    [Show full text]
  • DNA Stands for Deoxyribose Nucleic Acid
    DNA and Protein Synthesis DNA • DNA stands for deoxyribose nucleic acid. • This chemical substance is found in the nucleus of all cells in all living organisms • DNA controls all the chemical changes which take place in cells • The kind of cell which is formed, (muscle, blood, nerve etc) is controlled by DNA Ribose is a sugar, like glucose, but with only five carbon atoms in its molecule. Deoxyribose is almost the same but lacks one oxygen atom. The nitrogen bases are: o ADENINE (A) o THYMINE (T) o CYTOSINE (C) o GUANINE (G) Nucleotides • A molecule of DNA is formed by millions of nucleotides joined together in a long chain. • DNA is a very large molecule made up of a long chain of sub-units. • The sub-units are called nucleotides. • Each nucleotide is made up of a sugar called deoxyribose, a phosphate group -PO4 and an organic (Nitrogen) base: A, T, C, G BASE PAIRING RULE amount of C= amount of G AND amount of A= amount of T • Adenine always pairs with thymine, and guanine always pairs with cytosine. DNA STRUCTURE • The nucleotide bases will point to the inside of the DNA molecule while the outside (backbone) of the DNA molecule will be made of the sugar and phosphate molecules. • When complete the DNA molecule forms a double helix (two spiral sides wrapped together). • The paired strands are coiled into a spiral called A DOUBLE HELIX. Genes • Each chromosome contains hundreds of genes. • Most of your characteristics: hair color, height, how things taste to a person, are determined by the kinds of proteins cells make (gene).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,604,000 B2 De Kort Et Al
    USOO8604000B2 (12) United States Patent (10) Patent No.: US 8,604,000 B2 de Kort et al. (45) Date of Patent: Dec. 10, 2013 (54) PALATABLE NUTRITIONAL COMPOSITION 2011/0027391 A1 2/2011 De Kort et al. COMPRISING ANUCLEOTDE AND/ORA 2013, OO12469 A1 1/2013 De Kort et al. NUCLEOSDE AND A TASTE MASKING 2013, OO18012 A1 1/2013 Hageman et al. AGENT FOREIGN PATENT DOCUMENTS (75) Inventors: Esther Jacqueline de Kort, Wageningen EP O 175468 A2 3, 1986 (NL); Martine Groenendijk, EP 1216 041 B1 6, 2002 EP 1282 365 B1 2, 2003 Barendrecht (NL); Patrick Joseph EP 1656 839 A1 5, 2006 Gerardus Hendrikus Kamphuis, EP 1666 092 A2 6, 2006 Utrecht (NL) EP 18OO 675 A1 6, 2007 JP 64-080250 A 3, 1989 (73) Assignee: N.V. Nutricia, Zoetermeer (NL) JP 06-237734. A 8, 1994 JP 10-004918 A 1, 1998 JP 10-136937 A 5, 1998 (*) Notice: Subject to any disclaimer, the term of this JP 11-071274. A 3, 1999 patent is extended or adjusted under 35 WO WO-0038829 A1 T 2000 U.S.C. 154(b) by 213 days. WO WO-01 (32034 A1 5, 2001 WO WO-02/088159 A1 11, 2002 WO WO-02/096464 A1 12/2002 (21) Appl. No.: 12/809,431 WO WO-03 (013276 A1 2, 2003 WO WO-03/041701 A2 5, 2003 (22) PCT Filed: Dec. 22, 2008 WO WO-2005/039597 A2 5, 2005 WO WO-2006/031683 A2 3, 2006 (86). PCT No.: PCT/NL2O08/050843 WO WO-2006,118665 A2 11/2006 WO WO-2006, 127620 A2 11/2006 S371 (c)(1), WO WO-2007/001883 A2 1, 2007 (2), (4) Date: Dec.
    [Show full text]
  • Synthesis of Alkynyl Ribofuranosides
    City University of New York (CUNY) CUNY Academic Works Dissertations and Theses City College of New York 2011 Synthesis of Alkynyl Ribofuranosides Christian Rodriguez CUNY City College How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/cc_etds_theses/25 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] SYNTHESIS OF ALKYNYL RIBOFURANOSIDES A Thesis Presented to The Faculty of the Chemistry Program The City College of New York In (Partial) Fulfillment of the Requirements for the Degree Master of Arts by Christian Rodriguez December, 2010 - 1 - Synthesis of Alkynyl Ribofuranosides By Christian Rodriguez Mentor: P. Meleties Table of Contents Chapter 1 1.1 Introduction 6 1.2 Preparation of ribonolactone template 8 1.3 Synthesis of protected ribonolactone 9 Chapter 2 2.1 Preparation of ethynyl ribofuranosides 10 2.2 Reaction with ethynylmagnesium bromide 12 2.3 Intramolecular cyclization of diyne diol 14 2.4 Reaction of ribonolactone with lithium acetylide 15 2.5 Boron trifluoride hemiacetal deoxygenation 15 2.6 Alternative deacetylation 16 Chapter 3 3.1 Selecting appropriate protecting group 19 3.2 Preparation of trimethylsilyl alkynyl 5-O-benzyl-2,3-O isopropylidene 19 ribofuranoside 3.3 Lewis acid promoted triethylsilane dehydroxylation mechanism 20 Chapter 4 4.1 Hemiacetal alkynylation 25 4.2 Hemiacetal nucleophilic addition mechanism 26 4.3 Intramolecular
    [Show full text]
  • Nucleosides & Nucleotides
    Nucleosides & Nucleotides Biochemistry Fundamentals > Genetic Information > Genetic Information NUCLEOSIDE AND NUCLEOTIDES SUMMARY NUCLEOSIDES  • Comprise a sugar and a base NUCLEOTIDES  • Phosphorylated nucleosides (at least one phosphorus group) • Link in chains to form polymers called nucleic acids (i.e. DNA and RNA) N-BETA-GLYCOSIDIC BOND  • Links nitrogenous base to sugar in nucleotides and nucleosides • Purines: C1 of sugar bonds with N9 of base • Pyrimidines: C1 of sugar bonds with N1 of base PHOSPHOESTER BOND • Links C3 or C5 hydroxyl group of sugar to phosphate NITROGENOUS BASES  • Adenine • Guanine • Cytosine • Thymine (DNA) 1 / 8 • Uracil (RNA) NUCLEOSIDES • =sugar + base • Adenosine • Guanosine • Cytidine • Thymidine • Uridine NUCLEOTIDE MONOPHOSPHATES – ADD SUFFIX 'SYLATE' • = nucleoside + 1 phosphate group • Adenylate • Guanylate • Cytidylate • Thymidylate • Uridylate Add prefix 'deoxy' when the ribose is a deoxyribose: lacks a hydroxyl group at C2. • Thymine only exists in DNA (deoxy prefix unnecessary for this reason) • Uracil only exists in RNA NUCLEIC ACIDS (DNA AND RNA)  • Phosphodiester bonds: a phosphate group attached to C5 of one sugar bonds with - OH group on C3 of next sugar • Nucleotide monomers of nucleic acids exist as triphosphates • Nucleotide polymers (i.e. nucleic acids) are monophosphates • 5' end is free phosphate group attached to C5 • 3' end is free -OH group attached to C3 2 / 8 FULL-LENGTH TEXT • Here we will learn about learn about nucleoside and nucleotide structure, and how they create the backbones of nucleic acids (DNA and RNA). • Start a table, so we can address key features of nucleosides and nucleotides. • Denote that nucleosides comprise a sugar and a base.
    [Show full text]
  • Production of Natural and Rare Pentoses Using Microorganisms and Their Enzymes
    EJB Electronic Journal of Biotechnology ISSN: 0717-3458 Vol.4 No.2, Issue of August 15, 2001 © 2001 by Universidad Católica de Valparaíso -- Chile Received April 24, 2001 / Accepted July 17, 2001 REVIEW ARTICLE Production of natural and rare pentoses using microorganisms and their enzymes Zakaria Ahmed Food Science and Biochemistry Division Faculty of Agriculture, Kagawa University Kagawa 761-0795, Kagawa-Ken, Japan E-mail: [email protected] Financial support: Ministry of Education, Science, Sports and Culture of Japan under scholarship program for foreign students. Keywords: enzyme, microorganism, monosaccharides, pentose, rare sugar. Present address: Scientific Officer, Microbiology and Biochemistry Division, Bangladesh Jute Research Institute, Shere-Bangla Nagar, Dhaka- 1207, Bangladesh. Tel: 880-2-8124920. Biochemical methods, usually microbial or enzymatic, murine tumors and making them useful for cancer treatment are suitable for the production of unnatural or rare (Morita et al. 1996; Takagi et al. 1996). Recently, monosaccharides. D-Arabitol was produced from D- researchers have found many important applications of L- glucose by fermentation with Candida famata R28. D- arabinose in medicine as well as in biological sciences. In a xylulose can also be produced from D-arabitol using recent investigation, Seri et al. (1996) reported that L- Acetobacter aceti IFO 3281 and D-lyxose was produced arabinose selectively inhibits intestinal sucrase activity in enzymatically from D-xylulose using L-ribose isomerase an uncompetitive manner and suppresses the glycemic (L-RI). Ribitol was oxidized to L-ribulose by microbial response after sucrose ingestion by such inhibition. bioconversion with Acetobacter aceti IFO 3281; L- Furthermore, Sanai et al. (1997) reported that L-arabinose ribulose was epimerized to L-xylulose by the enzyme D- is useful in preventing postprandial hyperglycemia in tagatose 3-epimerase and L-lyxose was produced by diabetic patients.
    [Show full text]