DOCSLIB.ORG

ATROPINE Abdullah A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
ATROPINE Abdullah A ATROPINE Abdullah A. Al-Badr and Farid J. Muhtadi King Saud University Riyadh, Saudi Arabia 1. Description 326 1.1 Nomenclature 326 1.2 Formulae 326 1.3 Molecular Weight 328 1.4 Elemental Composition 328 1.5 Appearance, Color, Odor, and Taste 328 I .6 Dissociation Constant 328 1.7 pH range 328 2. Physical Properties 329 2. I Melting Point 329 2.2 Sublimation Range 329 2.3 Solubility 329 2.4 X-Ray Crystallography 329 2.5 Spectral Properties 330 3. Isolation 340 4. Synthesis 340 4.1 Partial Synthesis 340 4.2 Total Synthesis 340 5. Biosynthesis 352 5.1 Biosynthesis of Tropine 352 5.2 Biosynthesis of Tropic Acid 354 6. Metabolism 355 7. Pharmacokinetics 357 8. Therapeutic Uses of Atropine 358 9. Methods of Analysis 359 9.1 Identification Tests 359 9.2 Microcrystal Tests 360 9.3 Titrimetric Methods 360 9.4 Polarographic Methods 365 9.5 SpectrophotometricMethods 366 9.6 Chromatographic Methods 373 9.7 Radio-immunoassay 378 References 380 ANALYTICAL PROFILES OF DRUG SUBSTANCES Copyright 0 1985 VOLUME 14 325 by the American Pharmaceutical Association ISBN 0-12-260814-3 326 ABDULLAH A. AL-BADR AND FARID J. MUHTADI 1. Description 1.1 Nomenclature 1.1.1 Chemical Names a) endo ( f)- a -( Hydroxymethyl) benzene-acetic acid 8-methyl-8-azabicyclo [ 3.2.11 oct- 3-y1 ester. b) Benzene-acetic acid a-( hydroxymethy1)-, 8-methyl-8-azabicyclo [ 3.2.11 oct-3-yl ester, *-( +)- c) la H,-:a H-tropan-3a -ol( 2)-tropate. 1.1.2 Generic Names Atropine, dl-hyoscyamine, (2)-hyoscyamine, tropic acid ester with tropine, tropine (2) tropate, dl-tropyl tropate , (2) tropyl tropate . 1.2 Formulae 1.2.1 Ebpirical C H NO 17 23 3 1.2.2 Structural 7 6 The structure was confirmed by the total syn- thesis of atropine which was achieved by several authors ( 1-4 ) . ATROPINE 327 1.2.3 CAS Registry No. 51-55-8 I 1.2.4 Wiswesser Line Notation ~56A ANTJ A -GOVYR & 1Q- DL (5) 1.2.5 Stereochemistry Examination of the NMR spectra of some tropane deuterohalides has shown that the N-substitu- ent in tropanes is predominantly equatorial (61. X-ray analysis of tropine hydrobromide has shown the presence of chair conformation (7). Study of the dipole-moment and Kerr-constant measurements of a number of tropane derivati- ves has shown that the piperidine ring is in the chair form with the N-methyl equatorial (8). Another study of the dipole-moments and NMR spectra of some tropane derivatives have confirmed that the piperidine ring is in the chair conformation with the N-methyl group predominantly equatorial (9). In tropine, however, the predominant conformation is the piperidine ring in a deformed chair form to- gether with a minor amount in the boat form (10). HO Tropine In atropine, the a-3-substituent is of grea- ter bulk than the hydroxyl, and the boat form may will be favored because of the increased interactions involving the dimethylene bridge in the chair confirmation (11). ABDULLAH A. AL-BADR AND FARlD J. MUHTADI H N-CH3 0 11 NCH~OH 0-C-CH \ C6H5 A detailed review is available for the boat or chair conformation in tropines (12). Other PMR study suggested a preference for the boat conformation in several tropane derivatives. This study showed strong cross-ring intramolecular inter- actions of the type N--- C-=O and N---H-O were indi- cated by the broadening of the proton signal due to the coupling between 1(5)-H and 2(4)-H protons in the boat conformer compared with the chair. This broad- ening arises as a consequence of eclipsing of these protons in the boat conformer (13). Carbon-13 magne- tic resonance study has also suggested a non-chair conformations in tropane derivatives (14). 1.3 Molecular Weipht 289.38 1.4 Elemental Composition c, 70.56%; H, 8.01%; N, 4.84%; 0, 16.59% 1.5 Appearance, Color, Odor and Taste Colorless needle-like crystals or white crystalline powder, odorless and has a sharp bitter taste. 1.6 Dissociation Constant PKa 5.93 1.7 BH range pH of 0.0015 molar solution is 10.0 (15),approximate pH of saturated aqueous solution is 9.5 (16). ATROPINE 329 2. Physical Properties 2.1 Melting Point 114 - 116' (15) 114 - 118' (16) 2.2 Sublimation range Atropine sublimes in high vacuum at 93-110'. 2.3 Solubility One gram dissolves in 460 ml water, in 90 ml water at 80°, in 2 ml alcohol, 1.2 ml alcohol at 60°, in 27 ml glycerol, 25 ml ether. Soluble in benzene and dilute acids. 2.4 X-ray crystallography The X-ray crystallography of tropine hydrobromide (7), tropine ethobromide (17) pseudotropine (18) hyoscine hydrobromide (19) and tropic acid in hyoscine N-oxide (20 ) have been reported. 330 ABDULLAH A. AL-BADR AND FARID J. MUHTADI 2.5 Spectral Properties 2.5.1 Ultraviolet Spectrum The W spectrum of atropine in ethanol (Fig.1) was scanned from 200 to 400 nm using DMS 90 'Varian Spectrophotometer. It exhibited the following W data (Table 1). Table 1. UV characteristics of atropine A ma. at nm E A(1%, 1 cm) 20 5 - - 246 147.6 5.1 251.5 175.1 6.05 257 209.8 7-25 263.5 143.3 4.95 271 24.6 0.85 Other reported W spectral data for atropine in 0.1 N sulfuric acid ( 21 ) : h max at. 252 mu (E 1%, 1 cm 5), 258 mu (E I%, 1 cm 6) and 264 mu (E 1%,1 cm 5). 2.5.2 Infrared Spectrum The IR spectrum of atropine as KBr-disc was recorded on a Perkin Elmer 580 B Infrared Spectrophotometer to which Infrared Data stat- ion is attached (Fig. 2). The structural assignments have been correla- ted with the following frequencies (Table 2). Table 2. IR Characteristics of Atropine -1 Frequency cm Assignment 3070 OH (hydrogen bonded) 2930 CH (stretch) 2810 N-CH B 3 1725 0-C - (ester) 1595, 1580 C=C aromatic FIG, 1, THE UV SPECTRUM OF ATROPINE IN ETHANOL 44. i &O# WAVE##H#FR #o asM 2060 fm YO0 1400 1000 800 680 & FIG. 2, THE IR SPECTRUM OF ATROPINE AS KBR-DISC ATROPINE 333 -1 Frequency cm Assignment 1155, 1030 C-0-C (ether ) 770,725,690 5H (mono substituted aromatics) The IR exhibited the following other characteristic bands :- 1450,1420,1370,1355,1335,1270,12~5,~230,~220,~205, 1190,1165,1132,1108,1065,975,920,845,805,515 cm-1. Other IR data for atropine (5,21) have been also reported. 2.5.3 Nuclear Magnetic Resonance Spectra 2.5.3.1 Proton Spectra The PMR spectra of both atropine in CDC13 and in TFA (Trifluoroacetic acid) were recorded on a Varian T- ~OA,60 MHz NMR Spectrometer using TMS (Tetramethylsilane) as an inter- nal reference. These are shown in Fig. 3(a) and 3{b) respectively. The following structural assignments have been made (Table 3). 8 0- C- 9 Other PMR data for atropine are also reported (5,9, 13,22). 3 34 ABDULLAH A. AL-BADR AND FARID J. MUHTADI I 1 I. I I .. I I .I ., ..I. ... I .. .. i ,I,. i , , LO TO 40 a# Rn(,) u B.# 1.. 1.0 FIG.3IA). TPE PYR SPECTnWi OF ATROPI3E Ill CDCL~ ATROPINE 335 Table 3. PMR characteristics of atropine Group Chemical Shift (ppm) CDC13 TFA 5 aromatic protons 7.23(s) 7.36( s 1 13,lb ,15,16,17 3-H 3-H CH2 - OH CH2 - OH, 10 CH- 135 H 8-N-Me 2,4,6,7 H s=singlet , d=doublet , t=triplet , bs=broad singlet , m=mult iplet 2.5.3.2 13C-NMR The I3C-NMR noise decoupled and off resonance spectra are presented in Fig. 4 and Fig. 5 respectively. Both were recorded over 4000 Hz range in deuterated chloroform on a Varian FT 80 A-80 MHz spectrometer, using 10 mm sample tube and tetramethyl sil- ane as a reference standard at 21'. The carbon chemical shifts are assi- gned on the bases of the additivity principals and off resonance splitt- ing pattern (Table 4). 8 11 15 4 10 17 16 336 ABDULLAH A. AL-BADR AND FARID J. MUHTADI d 111 FIG. 4. THE I3C-NER NOISE DECOUPLED SPECTRUE OF ATROPINE I ATROPINE 337 Table 4. Carbon Chemical Shifts of Atropine Carbon no. Chemical Shift Carbon no. Chemical Shift [PPd [PP~ C 171.92( s ) 59.54(d) 9 c1 c5 136.17 ( s ( d) 52 1 ‘10 54.94 ‘13’ ‘17 128.66( d) ‘8 40.08(q) 128.11 (d) 36.04(t ‘14’ ‘16 c23 c4 127.48 ( d) C 25.31(t) ‘15 7 C 24.93(t 3 67.63 ( d) ‘6 1 cll 63.54(t) s=singlet , d=doublet t=triplet q=quartet . Other l3C-NMR data for atropine ( 14,23 ) atropine hydrochloride (14) and atropine methoiodide (14) have also been reported. 2.5.4 Mass Spectrum The mass spectrum of atropine is presented in Fig. 6. This was obtained by electron im- pact ionization on a Varian MAT 1020 by direct inlet probe at 270’~. The electron energy was 70 eV. The spectrum scanned to mass 300 amu. The spectrum (Fig. 6) shows a molecular ion peak M+ at m/e 289 with relative intensity 9.50%. The base peak is 124 with relative intensity 100%. The most prominent fragments their relative intensities and some proposed ion fragments are given in table 5.
Load more

Recommended publications
  • Hexafluorophosphate Salts with Tropine-Type Cations in The
    RSC Advances PAPER View Article Online View Journal | View Issue Hexafluorophosphate salts with tropine-type cations in the extraction of alkaloids with the same Cite this: RSC Adv.,2018,8,262 nucleus from radix physochlainae† Bing Dong, Jie Tang, Alula Yonannes and Shun Yao * Ionic liquids (ILs) have been widely used in the field of extraction of natural bioactive compounds because of their advantages compared to traditional organic solvents. In this study, the new ‘like dissolves like’ mode was designed and seven types of tropine-based ionic liquids were used to extract tropane alkaloids from radix physochlainae, and then the relationship between their performance and structures together with À1 the effects of main extraction conditions were explored. It was found that 0.05 mol L [C3tr][PF6] aqueous solution had the ideal selectivity and high extraction efficiency of 95.1% at 75 C when the extraction time was 55 min and the solid–liquid ratio was 1 : 35, which was superior to that of 85% ethanol–water and 0.1% hydrochloric acid–water. There was no decomposition and racemization of Creative Commons Attribution-NonCommercial 3.0 Unported Licence. products occurring in the mixture solution when above extraction solvent was applied. In addition, the extraction behavior and mechanism using an ionic liquid aqueous solution was tentatively studied through thermodynamics experiments, near-infrared/infrared spectroscopy (NIR/IR), scanning electron Received 22nd November 2017 microscopy (SEM), and thermogravimetric analysis (TG), and subsequent back-extraction could be Accepted 14th December 2017 efficiently used to further separate alkaloids and ILs. In the developed ‘like dissolves like’ mode, the DOI: 10.1039/c7ra12687e extraction process of target alkaloids was found to be endothermic and spontaneous through the rsc.li/rsc-advances specific interaction between them and the solvent molecules with the same nucleus.
    [Show full text]
  • Tropane and Granatane Alkaloid Biosynthesis: a Systematic Analysis
    Office of Biotechnology Publications Office of Biotechnology 11-11-2016 Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis Neill Kim Texas Tech University Olga Estrada Texas Tech University Benjamin Chavez Texas Tech University Charles Stewart Jr. Iowa State University, [email protected] John C. D’Auria Texas Tech University Follow this and additional works at: https://lib.dr.iastate.edu/biotech_pubs Part of the Biochemical and Biomolecular Engineering Commons, and the Biotechnology Commons Recommended Citation Kim, Neill; Estrada, Olga; Chavez, Benjamin; Stewart, Charles Jr.; and D’Auria, John C., "Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis" (2016). Office of Biotechnology Publications. 11. https://lib.dr.iastate.edu/biotech_pubs/11 This Article is brought to you for free and open access by the Office of Biotechnology at Iowa State University Digital Repository. It has been accepted for inclusion in Office of Biotechnology Publicationsy b an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis Abstract The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring ot their core ring structures. Throughout much of human history, humans have cultivated tropane- and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis.
    [Show full text]
  • Introduction to Alkaloids
    MASARYKOVA UNIVERZITA Pedagogická fakulta Katedra fyziky, chemie a odborného vzdělávání Introduction to Alkaloids Bakalářská práce Brno 2017 Vedoucí práce: Autor práce: Mgr. Jiří Šibor, Ph.D. Aleš Bárta Prohlášení: „Prohlašuji, že jsem bakalářskou práci vypracoval samostatně, s využitím pouze citovaných pramenů, dalších informací a zdrojů v souladu s Disciplinárním řádem pro studenty Pedagogické fakulty Masarykovy univerzity a se zákonem č. 121/2000 Sb., o právu autorském, o právech souvisejících s právem autorským a o změně některých zákonů (autorský zákon), ve znění pozdějších předpisů.“ V Brně dne: 28.3.2017 ………………….. Aleš Bárta 2 Acknowledgement: I would like to thank to Mgr. Jiří Šibor, Ph.D. not only for the help he provided me with but also for his endless patience during our sessions which helped me complete this bachelor thesis. 3 Obsah INTRODUCTION AND GOALS .............................................................................................. 6 WORKING APPROACH .......................................................................................................... 7 1 ALKALOIDS – CHARACTERISTICS ................................................................................. 8 1.1 HISTORY OF ALKALOID CHEMISTRY ................................................................................ 11 1.2 SIGNIFICANCE OF ALKALOID FORMATION FOR THE PRODUCER ORGANISM .................... 11 1.3 APPLICATIONS ................................................................................................................... 11
    [Show full text]
  • Tropine Dehydrogenase: Purification, Some Properties and an Evaluation of Its Role in the Bacterial Metabolism of Tropine Barbara A
    Biochem. J. (1995) 307, 603-608 (Printed in Great Britain) 603 Tropine dehydrogenase: purification, some properties and an evaluation of its role in the bacterial metabolism of tropine Barbara A. BARTHOLOMEW, Michael J. SMITH, Marianne T. LONG, Paul J. DARCY, Peter W. TRUDGILL and David J. HOPPER* Institute of Biological Sciences, University of Wales, Aberystwyth, Dyfed SY23 3DD, Wales, U.K. Tropine dehydrogenase was induced by growth of Pseudomonas number of related compounds. The apparent Kms were 6.06 ,uM AT3 on atropine, tropine or tropinone. It was NADP+-dependent for tropine and 73.4,M for nortropine with the specificity and gave no activity with NADI. The enzyme was very unstable constant (Vmax/Km) for tropine 7.8 times that for pseudotropine. but a rapid purification procedure using affinity chromatography The apparent Km for NADP+ was 48 ,uM. The deuterium of [3- that gave highly purified enzyme was developed. The enzyme 2H]tropine and [3-2H]pseudotropine was retained when these gave a single band on isoelectric focusing with an isoelectric compounds were converted into 6-hydroxycyclohepta- 1 ,4-dione, point at approximately pH 4. The native enzyme had an Mr of an intermediate in tropine catabolism, showing that the tropine 58000 by gel filtration and 28000 by SDS/PAGE and therefore dehydrogenase, although induced by growth on tropine, is not consists of two subunits of equal size. The enzyme displayed a involved in the catabolic pathway for this compound. 6-Hydroxy- narrow range of specificity and was active with tropine and cyclohepta-1,4-dione was also implicated as an intermediate in nortropine but not with pseudotropine, pseudonortropine, or a the pathways for pseudotropine and tropinone catabolism.
    [Show full text]
  • Fifty Years of Alkaloid Biosynthesis in Phytochemistry Q ⇑ Geoffrey A
    Phytochemistry 91 (2013) 29–51 Contents lists available at SciVerse ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem Review Fifty years of alkaloid biosynthesis in Phytochemistry q ⇑ Geoffrey A. Cordell Natural Products Inc., Evanston, IL, USA Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA article info abstract Article history: An overview is presented of the studies related to the biosynthesis of alkaloids published in Phytochem- Available online 20 June 2012 istry in the past 50 years. Ó 2012 Elsevier Ltd. All rights reserved. Keywords: Alkaloids Biosynthesis Overview Contents 1. Introduction . ....................................................................................................... 30 1.1. Ornithine-derived alkaloids . .......................................................................... 30 1.2. Nicotine . .......................................................................................... 31 1.3. Tropane alkaloids . .......................................................................................... 33 1.4. Calystegines . .......................................................................................... 34 1.5. Pyrrolizidine alkaloids. .......................................................................................... 34 1.6. Retronecine . .......................................................................................... 34 1.7. Lysine-derived alkaloids . .........................................................................................
    [Show full text]
  • Synthesis of Novel Biologically Active Tropanes
    Synthesis of Novel Biologically Active Tropanes Anna L. Wallis A thesis subm Degree of Doctor Faculty of University July 1999 UMI Number: U133359 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI U133359 Published by ProQuest LLC 2014. Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 STATEMENT The accompanying thesis submitted for the degree of PhD entitled “Synthesis of Novel Biologically Active Tropanes” is based on work conducted by the author in the Department of Chemistry at the University of Leicester mainly during the period between October 1995 and October 1998. All work recorded in this thesis is original unless otherwise acknowledged in the text or references. None of the work has been submitted for another degree in this or any other university. Signed:. To Mum and (Dad ‘With Cove JLc^now(edgments Firstly, I would like to express my gratitude to John Malpass for his guidance and support over the past three years. I am also indebted to other members of staff in the department who have helped me during my PhD, in particular: Gerald Griffith for NMR spectroscopy; Graham Eaton for mass spectrometry; Mick Lee for his expert technical assistance and Martin Sparks for his cheerful and efficient help in the main store.
    [Show full text]
  • Laszlo Gyermek: the Role of the Tropane Skeleton in Drug Research
    1 Laszlo Gyermek: The role of the tropane skeleton in drug research This review describes certain reminiscences about an area of chemical pharmacology I have been involved with, on and off, for many years. Specifically, it focuses on tropane, a fascinating, naturally occurring bicyclic chemical ring system that lends itself to many pharmaceutical and therapeutic applications. My involvement with the tropane ring started more than 60 years ago in 1949, when, as a young assistant in the Institute of Pharmacology at the Medical Faculty of the University of Budapest, I started out to probe some, yet unexplored chemical pharmacological aspects of the best known tropane alkaloid, atropine, which is the tropic acid ester of tropine, the simplest, naturally occurring tropane compound, the structure of which is shown in Figure 1. The bicyclic ring system of tropane can be construed as a condensation product of a piperidine and pyrrolidine ring with a shared N atom as shown in Figure 2. Figure 3 calls attention to the numbering of the atoms of the tropane ring. Thus, the exact chemical name of tropane is: 8 Methyl azabicyclo (3.2.1) octane. This name also characterizes the manner of how this bicyclic ring system is branched, which has distinct pharmacological significance. 2 There exist about 230 naturally occurring tropane derivatives (Lounasmaa and Tamminen 1993). The number of synthetically produced tropane compounds is, however, much higher and runs to the thousands. As mentioned, tropine (or tropane-3-alpha-ol) with a molecular weight of 141.21 g/mol. and a molecular volume of 142 cubic Angstrom is the smallest tropane alkaloid, while the largest is grahamine, a trimer, with three fused tropane rings, with a molecular weight of 860 g/mol.
    [Show full text]
  • PRODUCT INFORMATION Tropine Item No
    PRODUCT INFORMATION Tropine Item No. 18627 CAS Registry No.: 120-29-6 Formal Name: (3-endo)-8-methyl-8- Azabicyclo[3.2.1]octan-3-ol Synonyms: NSC 43870, 3-Tropanol MF: C8H15NO N FW: 141.2 OH Purity: ≥95% Stability: ≥2 years at -20°C Supplied as: A crystalline solid Laboratory Procedures For long term storage, we suggest that tropine be stored as supplied at -20°C. It should be stable for at least two years. Tropine is supplied as a crystalline solid. A stock solution may be made by dissolving the tropine in the solvent of choice. Tropine is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide, which should be purged with an inert gas. The solubility of tropine in these solvents is approximately 30 mg/ml. Further dilutions of the stock solution into aqueous buffers or isotonic saline should be made prior to performing biological experiments. Ensure that the residual amount of organic solvent is insignificant, since organic solvents may have physiological effects at low concentrations. Organic solvent-free aqueous solutions of tropine can be prepared by directly dissolving the crystalline solid in aqueous buffers. The solubility of tropine in PBS, pH 7.2, is approximately 10 mg/ml. We do not recommend storing the aqueous solution for more than one day. Description Tropine is a naturally-occurring tropane alkaloid extracted primarily from plants of the Solanaceae family.1 It serves as an intermediate in the synthesis of a variety of bioactive alkaloids, including atropine (Item No. 12008), benztropine (Item No. 18214), and scopolamine, many of which have potent neurological actions.1,2 References 1.
    [Show full text]
  • Plant Tropane Alkaloid Biosynthesis Evolved Independently in the Solanaceae and Erythroxylaceae
    Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae Jan Jirschitzkaa, Gregor W. Schmidta, Michael Reichelta, Bernd Schneiderb, Jonathan Gershenzona, and John Charles D’Auriaa,1 aDepartment of Biochemistry, Max Planck Institute for Chemical Ecology, D-07745 Jena, Germany; and bNMR Research Group, Max Planck Institute for Chemical Ecology, D-07745 Jena, Germany Edited by Jerrold Meinwald, Cornell University, Ithaca, NY, and approved May 4, 2012 (received for review January 11, 2012) The pharmacologically important tropane alkaloids have a scat- Studies of the biosynthesis of tropane alkaloids have been tered distribution among angiosperm families, like many other predominantly performed with members of the Solanaceae and groups of secondary metabolites. To determine whether tropane to a lesser extent with cultivated species of the Erythroxylaceae. alkaloids have evolved repeatedly in different lineages or arise The majority of these studies used in vivo feeding of radiolabeled from an ancestral pathway that has been lost in most lines, we precursors (4–6) to elucidate the outlines of a general tropane investigated the tropinone-reduction step of their biosynthesis. In alkaloid biosynthetic pathway (7, 8). Biosynthesis is initiated species of the Solanaceae, which produce compounds such as from the polyamine putrescine, which is derived from the amino atropine and scopolamine, this reaction is known to be catalyzed acids ornithine or arginine (Fig. S1). Putrescine becomes N- by enzymes of the short-chain dehydrogenase/reductase family. methylated via the action of putrescine methyltransferase in what However, in Erythroxylum coca (Erythroxylaceae), which accumu- is generally considered to be the first committed step in tropane lates cocaine and other tropane alkaloids, no proteins of the short- alkaloid production (9).
    [Show full text]
  • Functional Heptagon-Centred Polyaromatics
    Durham E-Theses Functional Heptagon-Centred Polyaromatics TURLEY, ANDREW,THOMAS How to cite: TURLEY, ANDREW,THOMAS (2020) Functional Heptagon-Centred Polyaromatics, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/13533/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk Functional Heptagon-Centred Polyaromatics Andrew Thomas Turley A Thesis Submitted for the Degree of Doctor of Philosophy January 2020 Dedicated to my loving Friends and Family ii Table of Contents Abstract ...................................................................................................................... vii Declaration ............................................................................................................... viii Conferences Attended and Presentations Given ........................................................
    [Show full text]
  • United States Patent Office
    Patented Jan. 9, 1945 2,366,760 UNITED STATES PATENT OFFICE PRODUCTION OF TROPINE Jacob van de Kamp, Westfield, N.J., and Meyer Sletzinger, Bronx, N.Y., assignors to Merck & Co.,Jersey Inc., Rahway, N.J. ., a corporation of New No Drawing. Application June 5, 1942, '. Serial No. 445,988 4 Claims. (C1.260-292) This invention relates to the preparation of the hydrogen may be brought to reaction with tropine from tropinone. the tropinone solution in any other suitable man Several methods have been proposed in th ner Well known in the hydrogenation art. prior art for the reduction of tropinone to tropine, When operating within the preferred Scope. Of Such as electrolytic reduction, in acid or alka the invention, the conversion of tropinone to line media, reduction with zinc dust and hydro tropine is substantially quantitative. iodic acid and similar procedures. However, such The following example illustrates a method of prior art methods yield products containing rela tively large amounts of objectionable impurities, carrying out the present invention, but it is to be comprising among other products, pseudotropine understood that this example is given by way. and tropane (the oxygen-free base of tropine). 10 of illustration and not of limitation. ." Tropine is used in the synthesis of atropine, and Eacample When So used, the presence of appreciable To 10 parts by weight of tropinone dissolved amounts of the pseudo product causes difficulties in 100 parts by volume of absolute ethanol is in isolating a good yield of pure atropine or its added 0.5 part by weight of Raney nickel catalyst.
    [Show full text]
  • Monitoring of Tropane Alkaloids in Foods As
    FINAL REPORT Monitoring of tropane alkaloids in foods FS 102116 March 2017 J. Stratton, J. Clough, I. Leon, M. Sehlanova and S. MacDonald Fera Science Ltd. Page 1 of 103 This report has been produced by FeraScience Ltd. under a contract placed by the UK Food Standards Agency. The views expressed herein are not necessarily those of the funding body. Fera Science Ltd. warrants that all reasonable skill and care has been used in preparing this report. Notwithstanding this warranty, Fera Science Ltd. shall not be under any liability for loss of profit, business, revenues or any special indirect or consequential damage of any nature whatsoever or loss of anticipated saving or for any increased costs sustained by the client or his or her servants or agents arising in any way whether directly or indirectly as a result of reliance on this report or of any error or defect in this report. Page 2 of 103 1. Summary A literature review was undertaken to understand the potential sources of tropane alkaloids (TAs) in the diet. Following the literature review a sampling plan was developed to carry out a survey of UK foods to determine their tropane alkaloid content. Sources of contamination were identified as Datura type seeds and the increase of Convulvulus type weeds in fields of food crops. Sampling was carried out for the UK FSA and as a part of a wider EFSA survey. A total of 286 samples were analysed for TAs and calystegines for the EFSA survey. 227 UK samples (197 cereal products, 10 green beans and stir fry vegetables and 20 teas) were analysed for TAs, and 59 UK samples (44 potatoes and 15 aubergines) were analysed for calystegines as part of the EFSA survey.
    [Show full text]