DOCSLIB.ORG

Part I: Synthesis of Functionalized Bile Acids Towards The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Part I: Synthesis of Functionalized Bile Acids Towards The PART I: SYNTHESIS OF FUNCTIONALIZED BILE ACIDS TOWARDS THE CONSTRUCTION OF STEROIDAL MACROCYCLES. PART II: EVALUATION AND EXPANSION OF A MODULAR CARD GAME FOR TEACHING ORGANIC CHEMISTRY A DISSERTATION IN Chemistry and Pharmaceutical Sciences Presented to the Faculty of the University of Missouri-Kansas City in partial fulfillment of the requirements for the degree DOCTOR OF PHILOSOPHY by CHRISTOPHER ANTON KNUDTSON B.S., Saint Louis University 2004 M.S., Kansas University 2011 Kansas City, Missouri 2019 © 2019 CHRISTOPHER ANTON KNUDTSON ALL RIGHTS RESERVED PART I: SYNTHESIS OF FUNCTIONALIZED BILE ACIDS TOWARDS THE CONSTRUCTION OF STEROIDAL MACROCYCLES. PART II: EVALUATION AND EXPANSION OF A MODULAR CARD GAME FOR TEACHING ORGANIC CHEMISTRY Christopher A. Knudtson, Candidate for the Doctor of Philosophy Degree University of Missouri-Kansas City, 2019 ABSTRACT In Part I, the synthesis of chenodeoxychoic acid (CDCA) derivatives towards the construction of unique chemical architectures are reported. Building on previously described methods, CDCA based macrocycles with inner cavities have been synthesized and characterized. Attempts toward oxa-Michael coupling of CDCA monomers to form sulfonate ester linked dimmers is described. CDCA was also functionalized with terminal alkynes (pentynyl, hexynyl, and heptynyl) and aryl iodide and cyclized to from the respective macrocycles. These have been coupled together via oxygen-free Sonogashira reaction conditions to form large barrel-like steroidal architectures. These structures were investigated by 1H NMR, 13 C NMR spectroscopy, and HR-MS, and MALDI-TOF spectroscopy. In part II a game to teach organic chemistry, ChemKarta was evaluated as a teaching tool. Analysis of an undergraduate class’s impressions of the game showed that Chemkarta was an easy to learn and enjoyable game, but the amount of information in the game could be overwhelming for some students. Furthermore, the modular nature of the game was demonstrated by iii developing new cards to fit into the examined card set, as well as additional card sets to teach different subjects using the same game rules. iv The faculty listed below, appointed by the Dean of the School of Graduate Studies, have examined a dissertation titled “Synthesis of Functionalized Bile Acids towards the Construction of Steroidal Macrocycles and Evaluation and Expansion of a Modular Card Game for Teaching Organic Chemistry,” presented by Christopher A Knudtson, candidate for the Doctor of Philosophy degree, and certify that in their opinion it is worthy of acceptance. Supervisory Committee Theodore White, Ph.D., Committee Chair College of Biological and Chemical Science J. David Van Horn, Ph.D. Department of Chemistry Kathleen Kilway, Ph.D. Department of Chemistry Thomas Johnston, Ph.D. Department of Pharmaceutical Sciences Bi Botti “Celestin” Youan, Ph.D. Department of Pharmaceutical Sciences v Contents ABSTRACT ............................................................................................................................. iii LIST OF SCHEMES................................................................................................................ ix LIST OF TABLES ................................................................................................................... xi ACKNOWLEDGEMENTS .................................................................................................... xii PART I: SYNTHESIS OF FUNCTIONALIZED BILE ACIDS TOWARDS THE CONSTRUCTION OF STEROIDAL MACROCYCLES Chapter 1. INTRODUCTION ............................................................................................................. 1 1.1 Introduction ................................................................................................................ 1 1.1.1 A Brief Review of Macrocyclic and Supramolecular Chemistry ............................. 1 1.1.2 Bile Acid Derivatives: Preparation, Structure and Applications .............................. 4 1.2 Research Goals ......................................................................................................... 13 1.2.1 Project Aims...................................................................................................... 13 1.2.2 Proposed Methods .................................................................................................. 14 2. LITERATURE REVIEW ................................................................................................... 17 2.1 Introduction ................................................................................................................... 17 2.2 The Physiological Functions of Bile Acids ................................................................... 19 2.3 Methods for Diversification .......................................................................................... 20 2.3.1 Esterification ........................................................................................................... 21 2.3.2 Amidation ............................................................................................................... 24 2.3.3 Carbonylation ......................................................................................................... 30 2.3.4 Etherification .......................................................................................................... 32 2.3.5 Click Reaction ........................................................................................................ 34 2.3.6 Sonogashira Coupling............................................................................................. 44 2.4 Conclusion ..................................................................................................................... 48 3. OXA-MICHAEL STRATEGIES TOWARD CDCA DIMERS ..................................... 49 3.1 Introduction ................................................................................................................... 49 3.2 Results and discussion ................................................................................................... 52 3.2.1 Synthesis of oxa-Michael Macrocycles .................................................................. 52 3.2.2 Characterization of Functionalized Bile Acids ....................................................... 59 vi 3.3 Conclusion ..................................................................................................................... 62 3.4 Experimental Section .................................................................................................... 63 3.4.1 General Methods..................................................................................................... 63 3.4.2 Experimental Procedures ........................................................................................ 64 3.6 Supporting Spectra ........................................................................................................ 73 4. SYNTHESIS OF BILE ACIDS DERIVATIVES TOWARDS MACROCYCLE CONSTRUCTION VIA SONOGASHIRA COUPLING ....................................................... 91 4.1 Introduction ................................................................................................................... 91 4.2 Results and Discussion ................................................................................................. 95 4.2.1 Synthesis of Functionalized Steroid Macrocycles .................................................. 95 4.2.2 Characterization of Functionalized Bile Acids. .................................................... 105 4.3 Conclusion ................................................................................................................... 108 4.4 Experimental Section .................................................................................................. 109 4.4.1 General Methods................................................................................................... 109 4.4.2 Experimental Procedures ...................................................................................... 110 4.4.3 Supporting Spectra ............................................................................................... 136 REFERENCES ..................................................................................................................... 213 PART II: EVALUATION AND EXPANSION OF A MODULAR CARD GAME FOR TEACHING ORGANIC CHEMISTRY 5. EVALUATION AND EXPANSION OF CHEMKARTA ............................................... 226 5.1 Introduction ................................................................................................................. 226 5.1.1 The Benefits of Educational Gaming ................................................................... 226 5.2 Results and Discussion ................................................................................................ 229 5.2.1 Design and Set-up ................................................................................................. 229 5.2.2 Basic Rules...................................................................................................... 230 5.2.3 Evaluation ............................................................................................................. 234 5.2.4 Modular Development .......................................................................................... 240 5.3 Conclusion ..................................................................................................................
Load more

Recommended publications
  • International Journal of Scientific Research and Reviews
    Saha Sudipta, IJSRR 2018, 7(3), 1749-1768 Review article Available online www.ijsrr.org ISSN: 2279–0543 International Journal of Scientific Research and Reviews Novel Antitussive Agents from Natural Source-A Review Saha Sudipta* Assistant Professor, Department of Chemistry, TrivenideviBhalotia College, Raniganj, PaschimBardhaman, West-Bengal, India, Pin-713347 Email: [email protected]; Mobile No:-+91-94343486121 ABSTRACT Cough, acts as the defender of the foreign materials and secretions from the airways. Cough gives the protection of the lungs and distal parts of airways from chocking and infected mucus. Cough is one of the major worldwide problem as patients suffering from this visit physician. In this way it leads to the economical problem in the society. The mostly used and available antitussive agents in the markets are codeine and dextromethorphan. Although they are good cough suppressing but they have also numerous side effects e.g., sedation, nausea, addictive potential, and constipation. Although a new class of antitussive drugs are not coming into the market for a long time. To solve this problem pharmacists and researchers are searching novel, less toxic, more effective antitussive drugs from the nature. Plant derived medicines act as the supplementary to the synthetic drugs followed by engineered protein and gene therapy. In this context pharmacotherapy provides some novel alkaloids, triterpenoids, phenolglycosides, polysaccharides, flavonoids, as more effective and less toxic antitussive agents. These said phytochemicals isolated from botanical source play a major role in the treatment of many respiratory diseases including cough. Some of the above mentioned extracts from the shrubs are used in the Indian traditional medicine, they can be used as a safe antitussive agents.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2013/0253056A1 Nemas Et Al
    US 20130253 056A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0253056A1 Nemas et al. (43) Pub. Date: Sep. 26, 2013 (54) CONTINUOUS ADMINISTRATION OF (60) Provisional application No. 61/179,511, filed on May LEVODOPA AND/OR DOPA 19, 2009. DECARBOXYLASE INHIBITORS AND COMPOSITIONS FOR SAME Publication Classification (71) Applicant: NEURODERM, LTD., Ness-Ziona (IL) (51) Int. Cl. A63L/216 (2006.01) (72) Inventors: Mara Nemas, Gedera (IL); Oron (52) U.S. Cl. Yacoby-Zeevi, Moshav Bitsaron (IL) CPC .................................... A6 IK3I/216 (2013.01) USPC .......................................................... 514/538 (73) Assignee: Neuroderm, Ltd., Ness-Ziona (IL) (57) ABSTRACT (21) Appl. No.: 13/796,232 Disclosed herein are for example, liquid aqueous composi (22) Filed: Mar 12, 2013 tions that include for example an ester or salt of levodopa, or an ester or salt of carbidopa, and methods for treating neuro Related U.S. Application Data logical or movement diseases or disorders such as restless leg (63) Continuation-in-part of application No. 12/961,534, syndrome, Parkinson's disease, secondary parkinsonism, filed on Dec. 7, 2010, which is a continuation of appli Huntington's disease, Parkinson's like syndrome, PSP. MSA, cation No. 12/836,130, filed on Jul. 14, 2010, now Pat. ALS, Shy-Drager syndrome, dystonia, and conditions result No. 7,863.336, which is a continuation of application ing from brain injury including carbon monoxide or manga No. 12/781,357, filed on May 17, 2010, now Pat. No. nese intoxication, using Substantially continuous administra 8,193,243. tion of levodopa and/or carbidopa or ester and/or salt thereof.
    [Show full text]
  • Parkinson Disease-Associated Cognitive Impairment
    PRIMER Parkinson disease-associated cognitive impairment Dag Aarsland 1,2 ✉ , Lucia Batzu 3, Glenda M. Halliday 4, Gert J. Geurtsen 5, Clive Ballard 6, K. Ray Chaudhuri 3 and Daniel Weintraub7,8 Abstract | Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment. Parkinson disease (PD) is the most common movement The full spectrum of cognitive impairment occurs in disorder and the second most common neurodegenera­ individuals with PD, from subjective cognitive decline tive disorder after Alzheimer disease (AD).
    [Show full text]
  • Azilect, INN-Rasagiline
    SCIENTIFIC DISCUSSION 1. Introduction AZILECT is indicated for the treatment of idiopathic Parkinson’s disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations. Rasagiline is administered orally, at a dose of 1 mg once daily with or without levodopa. Parkinson’s disease is a common neurodegenerative disorder typified by loss of dopaminergic neurones from the basal ganglia, and by a characteristic clinical syndrome with cardinal physical signs of resting tremor, bradikinesia and rigidity. The main treatment aims at alleviating symptoms through a balance of anti-cholinergic and dopaminergic drugs. Parkinson’s disease (PD) treatment is complex due to the progressive nature of the disease, and the array of motor and non-motor features combined with early and late side effects associated with therapeutic interventions. Rasagiline is a chemical inhibitor of the enzyme monoamine oxidase (MAO) type B which has a major role in the inactivation of biogenic and diet-derived amines in the central nervous system. MAO has two isozymes (types A and B) and type B is responsible for metabolising dopamine in the central nervous system; as dopamine deficiency is the main contributing factor to the clinical manifestations of Parkinson’s disease, inhibition of MAO-B should tend to restore dopamine levels towards normal values and this improve the condition. Rasagiline was developed for the symptomatic treatment of Parkinson’s disease both as monotherapy in early disease and as adjunct therapy to levodopa + aminoacids decarboxylase inhibitor (LD + ADI) in patients with motor fluctuations. 2. Quality Introduction Drug Substance • Composition AZILECT contains rasagiline mesylate as the active substance.
    [Show full text]
  • Cv1p0149.Pdf
    A Publication of Reliable Methods for the Preparation of Organic Compounds Working with Hazardous Chemicals The procedures in Organic Syntheses are intended for use only by persons with proper training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011; the full text can be accessed free of charge at http://www.nap.edu/catalog.php?record_id=12654). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices. In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red “Caution Notes” within a procedure. It is important to recognize that the absence of a caution note does not imply that no significant hazards are associated with the chemicals involved in that procedure. Prior to performing a reaction, a thorough risk assessment should be carried out that includes a review of the potential hazards associated with each chemical and experimental operation on the scale that is planned for the procedure. Guidelines for carrying out a risk assessment and for analyzing the hazards associated with chemicals can be found in Chapter 4 of Prudent Practices. The procedures described in Organic Syntheses are provided as published and are conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
    [Show full text]
  • Genl:VE 1970 © World Health Organization 1970
    Nathan B. Eddy, Hans Friebel, Klaus-Jiirgen Hahn & Hans Halbach WORLD HEALTH ORGANIZATION ORGANISATION .MONDIALE DE LA SANT~ GENl:VE 1970 © World Health Organization 1970 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. Nevertheless governmental agencies or learned and professional societies may reproduce data or excerpts or illustrations from them without requesting an authorization from the World Health Organization. For rights of reproduction or translation of WHO publications in toto, application should be made to the Division of Editorial and Reference Services, World Health Organization, Geneva, Switzerland. The World Health Organization welcomes such applications. Authors alone are responsible for views expressed in signed articles. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Director-General of the World Health Organization concerning the legal status of any country or territory or of its authorities, or concerning the delimitation of its frontiers. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. © Organisation mondiale de la Sante 1970 Les publications de l'Organisation mondiale de la Sante beneficient de la protection prevue par les dispositions du Protocole n° 2 de la Convention universelle pour la Protection du Droit d'Auteur. Les institutions gouvernementales et les societes savantes ou professionnelles peuvent, toutefois, reproduire des donnees, des extraits ou des illustrations provenant de ces publications, sans en demander l'autorisation a l'Organisation mondiale de la Sante. Pour toute reproduction ou traduction integrate, une autorisation doit etre demandee a la Division des Services d'Edition et de Documentation, Organisation mondiale de la Sante, Geneve, Suisse.
    [Show full text]
  • Multicatalytic, Asymmetric Michael/Stetter Reaction Of
    Multicatalytic, asymmetric Michael/Stetter reaction SPECIAL FEATURE of salicylaldehydes and activated alkynes Claire M. Filloux, Stephen P. Lathrop, and Tomislav Rovis1 Department of Chemistry, Colorado State University, Fort Collins, CO 80523 Edited by David W. C. MacMillan, Princeton University, Princeton, NJ, and accepted by the Editorial Board May 30, 2010 (received for review March 22, 2010) We report the development of a multicatalytic, one-pot, asymmetric Ar Ar Michael/Stetter reaction between salicylaldehydes and electron- N H deficient alkynes. The cascade proceeds via amine-mediated OO 3 OTMS (20 mol %) Me HO Me Michael addition followed by an N-heterocyclic carbene-promoted Me Me 1 Ar = 3,5-(CF3)2C6H3 O intramolecular Stetter reaction. A variety of salicylaldehydes, dou- + O O BF4 N bly activated alkynes, and terminal, electrophilic allenes participate 2 Me 5 Me in a one-step or two-step protocol to give a variety of benzofura- NNC F 4a 6 5 One-Pot Two - Po t none products in moderate to good yields and good to excellent (10 mol %) 93% yield 46% yield NaOAc (10 mol %) 85:15:<1:<1 dr 5:1 dr enantioselectivities. The origin of enantioselectivity in the reaction 86% ee 58% ee CHCl3, 23 C is also explored; E∕Z geometry of the reaction intermediate as well as the presence of catalytic amounts of catechol additive are O found to influence reaction enantioselectivity. O Me * O Me ∣ ∣ catalysis organic synthesis tandem catalysis Me 6 ascade catalysis has garnered significant recent attention Scheme 1. Multicatalytic Michael/Benzoin cascade. Cfrom the synthetic community as a means to swiftly assemble CHEMISTRY complex molecules from simple starting materials with minimal benzofuranones.
    [Show full text]
  • UNIVERSITE DE NANTES Thomas Gelineau
    UNIVERSITE DE NANTES __________ FACULTE DE MEDECINE __________ Année 2011 N° 139 THESE pour le DIPLÔME D’ÉTAT DE DOCTEUR EN MÉDECINE DES de médecine générale par Thomas Gelineau né le 29 janvier 1983 à Cholet __________ Présentée et soutenue publiquement le 06/12/2011 __________ LE RHUME DE L'ENFANT ET SON TRAITEMENT: DECISION PARTAGEE AVEC LES PARENTS D'APRES UN QUESTIONNAIRE __________ Président : Monsieur le Professeur Olivier MALARD Directeur de thèse : Madame le Professeur Jacqueline LACAILLE 1 Table des matières IIntroduction................................................................................................................ 7 IIDéfinition, état des connaissances...........................................................................8 1Le rhume.......................................................................................................................................8 APhysiopathologie............................................................................................................................. 8 aL'origine virale.................................................................................................................................... 8 bLa saisonnalité................................................................................................................................... 8 cL'âge de survenue.............................................................................................................................. 9 dLe sexe..................................................................................................................................................
    [Show full text]
  • Note to Users
    NOTE TO USERS This reproduction is the best copy available Synthetic Approaches to Coniochaetones A & B Leo James Patrick Martyn A thesis submitted in conformity with the requirements for the degree of Master of Science Graduate Department of Chemistry University of Toronto @ Copyright by Leo James Patrick Martyn 1999 National Library Bibliothèque nationale * of Canada du Canada Acquisitions and Acquisitions et Bibliographie Services seMces bibliographiques 395 Wellington Street 395, nie Wellington OltawaûN KIAW OnawaON K1AW Canada Canada The author has granted a non- L'auteur a accordé une licence non exclusive licence allowing the exclusive permettant à la National Library of Canada to Bibliothèque nationale du Canada de reproduce, loan, distribute or seU reproduire, prêter, distribuer ou copies of this thesis in microform, vendre des copies de cette thèse sous paper or electronic formats. la forme de microfiche/film, de reproduction sur papier ou sur format électronique. The author retains ownership of the L'auteur conserve la propriété du copyright in this thesis. Neither the droit d'auteur qui protège cette thèse. thesis nor substantial extracts fiom it Ni la thèse ni des extraits substantiels may be printed or otherwise de celle-ci ne doivent être imprimés reproduced without the author's ou autrement reproduits sans son permission. autorisation. Abstract Several routes to the synthesis of coniochaetones A and B, two natural products isolated from a liquid culture of Coniochaeta soccardoi,' were explored. Two different pathways which we believe will eventually lead to the synthesis of coniochaetones A and B have been focused upon. Utilizing a mode1 senes, key intermediates for each synthetic route have been synthesized and characterized.
    [Show full text]
  • 3 Drugs That May Cause Delirium Or Problem Behaviors CARD 03 19 12 JUSTIFIED.Pub
    Drugs that May Cause Delirium or Problem Behaviors Drugs that May Cause Delirium or Problem Behaviors This reference card lists common and especially problemac drugs that may Ancholinergics—all drugs on this side of the card. May impair cognion cause delirium or contribute to problem behaviors in people with demena. and cause psychosis. Drugs available over‐the‐counter marked with * This does not always mean the drugs should not be used, and not all such drugs are listed. If a paent develops delirium or has new problem Tricyclic Andepressants Bladder Anspasmodics behaviors, a careful review of all medicaons is recommended. Amitriptyline – Elavil Darifenacin – Enablex Be especially mindful of new medicaons. Clomipramine – Anafranil Flavoxate – Urispas Desipramine – Norpramin Anconvulsants Psychiatric Oxybutynin – Ditropan Doxepin – Sinequan Solifenacin – VESIcare All can cause delirium, e.g. All psychiatric medicaons should be Imipramine – Tofranil Tolterodine – Detrol Carbamazepine – Tegretol reviewed as possible causes, as Nortriptyline – Aventyl, Pamelor Gabapenn – Neuronn effects are unpredictable. Trospium – Sanctura Anhistamines / Allergy / Leveracetam – Keppra Notable offenders include: Insomnia / Sleep Valproic acid – Depakote Benzodiazepines e.g. Cough & Cold Medicines *Diphenhydramine – Sominex, ‐Alprazolam – Xanax *Azelasne – Astepro Pain Tylenol‐PM, others ‐Clonazepam – Klonopin *Brompheniramine – Bromax, All opiates can cause delirium if dose *Doxylamine – Unisom, Medi‐Sleep ‐Lorazepam – Avan Bromfed, Lodrane is too high or
    [Show full text]
  • Drug-Induced Movement Disorders
    Medical Management of Early PD Samer D. Tabbal, M.D. May 2016 Associate Professor of Neurology Director of The Parkinson Disease & Other Movement Disorders Program Mobile: +961 70 65 89 85 email: [email protected] Conflict of Interest Statement No drug company pays me any money Outline So, you diagnosed Parkinson disease .Natural history of the disease .When to start drug therapy? .Which drug to use first for symptomatic treatment? ● Levodopa vs dopamine agonist vs MAOI Natural History of Parkinson Disease Before levodopa: Death within 10 years After levodopa: . “Honeymoon” period (~ 5-7 years) . Motor (ON/OFF) fluctuations & dyskinesias: ● Drug therapy effective initially ● Surgical intervention by 10-15 years - Deep brain stimulation (DBS) therapy Motor Response Dyskinesia 5-7 yrs >10 yrs Dyskinesia ON state ON state OFF state OFF state time time Several days Several hours 1-2 hour Natural History of Parkinson Disease Prominent gait impairment and autonomic symptoms by 20-25 years (Merola 2011) Behavioral changes before or with motor symptoms: . Sleep disorders . Depression . Anxiety . Hallucinations, paranoid delusions Dementia at anytime during the illness . When prominent or early: diffuse Lewy body disease Symptoms of Parkinson Disease Motor Symptoms Sensory Symptoms Mental Symptoms: . Cognitive and psychiatric Autonomic Symptoms Presenting Symptoms of Parkinson Disease Mood disorders: depression and lack of motivation Sleep disorders: “acting out dreams” and nightmares Early motor symptoms: Typically Unilateral . Rest tremor: chin, arms or legs or “inner tremor” . Bradykinesia: focal and generalized slowness . Rigidity: “muscle stiffness or ache” Also: (usually no early postural instability) . Facial masking with hypophonia: “does not smile anymore” or “looks unhappy all the time” .
    [Show full text]
  • Synthesis and Antidepressant Activity of Some New Coumarin Derivatives
    Scientia Pharmaceutica (Sci. Pharm.) 74, 193-216 (2005) O Osterreichische Apotheker-Verlagsgesellschafl m. b. H., Wien, Printed in Austria Synthesis and Antidepressant Activity of Some New Coumarin Derivatives Nehad A. Abdel-Latif Natural Compounds Department, National Research Centre, Dokki, Cairo, Egypt; E-mail: [email protected] Abstract The coumarin-3-cinnamoyl derivatives 2a-d were prepared via Claisen- Schmidt condensation of 3-acetylcoumarin 1 with different aromatic aldehydes. Cycloaddition reaction of 2b,e with guanidine and thiourea yielded the corresponding aminopyrmimidine 3a,b and thioxypyrimidine derivatives 4a,b, respectively. Compounds 4a,b were condensed with chloroacetic acid or 3- bromopropionic acid to yield coumarin 3-thiazolo-pyrimidine 5a,b and thiazinopyrimidine 6a,b derivatives, respectively. Compounds 4a,b were condensed with chloroacetic acid and aromatic aldehyde to yield the aryl methylene derivatives 7a,b which could be prepared directly by condensation of compounds 5a,b with aromatic aldehydes. Compounds 2a-e were condensed with malononitrile or ethyl cyano acetate in presence of ammonium acetate to yield cyanopyridine 8a,b and cyanopyridone 9a- d derivatives, respectively, which were prepared by condensation of 3- acetylcoumarin 1, malononitrile or ethylcyanoacetate and aromatic aldehydes in presence of ammonium acetate. Condensation of compounds 2a,b,e with o-phenylenediamine in refluxing ethanol led to the formation of 10a-c as intermediate, followed by cleavage by thermolysis to benzimidazole derivative 11 along with compounds 12a-c as mixture, which were obtained directly by fusion of a,&unsaturated ketones 2 with o- phenylene diamine at 200-220°C, while compound 11 could be prepared in pure form by fusion of 1 with o-phenylene diamine at the same temperature.
    [Show full text]