DOCSLIB.ORG

(Aminomethyl)Piperidine Derivatives

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(Aminomethyl)Piperidine Derivatives SYNTHESIS AND EVALUATION OF ΑLPHA-FLUORO ANALOGUES OF CAPSAICIN AND 2-(AMINOMETHYL)PIPERIDINE DERIVATIVES Thomas Moraux A Thesis Submitted for the Degree of PhD at the University of St. Andrews 2011 Full metadata for this item is available in Research@StAndrews:FullText at: http://research-repository.st-andrews.ac.uk/ Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/2094 This item is protected by original copyright This item is licensed under a Creative Commons License Synthesis and evaluation of α-fluoro analogues of capsaicin and 2-(aminomethyl)piperidine derivatives A thesis presented for the degree of Doctor of Philosophy to the School of Chemistry - University of St-Andrews Thomas Moraux April 2011 SUBMISSION OF PHD AND MPHIL THESES REQUIRED DECLARATIONS 1. Candidate’s declarations: I, Thomas Moraux, hereby certify that this thesis, which is approximately 35.000 words in length, has been written by me, that it is the record of work carried out by me and that it has not been submitted in any previous application for a higher degree. I was admitted as a research student in October 2005 and as a candidate for the degree of Doctor of Philosophy in August 2006; the higher study for which this is a record was carried out in the University of St Andrews between 2005 and 2010. Date …………………………….. signature of candidate ………………………………………………... 2. Supervisor’s declaration: I hereby certify that the candidate has fulfilled the conditions of the Resolution and Regulations appropriate for the degree of Doctor of Philosophy in the University of St Andrews and that the candidate is qualified to submit this thesis in application for that degree. Date ……………………………. signature of supervisor ………………………………………………... 3. Permission for electronic publication: In submitting this thesis to the University of St Andrews I understand that I am giving permission for it to be made available for use in accordance with the regulations of the University Library for the time being in force, subject to any copyright vested in the work not being affected thereby. I also understand that the title and the abstract will be published, and that a copy of the work may be made and supplied to any bona fide library or research worker, that my thesis will be electronically accessible for personal or research use unless exempt by award of an embargo as requested below, and that the library has the right to migrate my thesis into new electronic forms as required to ensure continued access to the thesis. I have obtained any third-party copyright permissions that may be required in order to allow such access and migration, or have requested the appropriate embargo below. The following is an agreed request by candidate and supervisor regarding the electronic publication of this thesis: Access to printed copy and electronic publication of thesis through the University of St Andrews. Date ………… signature of candidate ……………………… signature of supervisor ………..………… Acknowledgements I would like to express my gratitude to my supervisor Professor David O’Hagan, for having given me the opportunity to work in his group and for the numerous valuable discussions during my PhD. I would like to join to this acknowledgement all the technical staff at the School of Chemistry and the BMS for providing such outstanding working conditions. I thank Professor Alexandra M.Z. Slawin, Dr Tomas Lebl, Melanja Smith, Caroline Horsburgh and Peter Pogorzelec for their respective help in crystal structure, NMR analyses and mass spectroscopic analyses. This PhD also gave me the opportunity to meet numerous people, and I would like to thanks in particular the members of the DOH group, past and present. The three musketeers who read this work were Dr Nawaf Al-Maharzik, Dr Neil Keddie, Dr Michael Corr, and Dr Yi Wang. My thoughts are also going to the old-timers: Matthieu, Guillaume, Vincent, Nelly, Paul, Pitak, Romain, Dr Daniel Farran, Dr Margit Winkler… et al.! Finally, Stefan Lazy German, Maciek Cookie Monster, and particularly Danny Cheeky Chicken have made this lab the most enjoyable place to work in! Abbreviations ACN acetonitrile Bn benzyl br broad BuLi buthyl lithium CM cross-metathesis d doublet DAST diethylaminosulfur trifluoride DCM dichloromethane de diastereomeric excess DIEA diisopropylethyl amine DMAP 4-(N,N-dimethylamino)pyridine DMF N,N-dimethylformamide dr diastereomeric ratio ee enantiomeric excess eq equivalent Hz Hertz HRMS high resolution mass spectroscopy IR infrared spectroscopy J coupling constant LDA Litium diisopropyl amide m multiplet μmol micromol (10-6 mol) Mp melting point NFSI N-fluorobenzene sulfonimide NFOBS N-fluoro-O-benzenedisulfonimide NMR nuclear magnetic resonance ppm parts per million PTFE polytetrafluoroethylene RNA ribonucleic acid RTX resiniferatoxin rt room temperature s singlet t triplet TBAF N-tetrabutylammonium fluoride TfO trifluoromethanesulfonate (triflate) THF tetrahydrofurane TLC thin layer chromatography TMS trimethylsilyl TRPV1 transient receptor potential vanilloid subtype 1 TsO p-methyl benzene sulfonate (tosyl) 19F NMR fluorine nuclear magnetic resonance 19F{1H} NMR proton decoupled fluorine nuclear magnetic resonance Table of contents Chapter 1- Fluorine in bioactive molecules 1.1- Discovery and development of fluorine chemistry 1 1.2- Controversial effects of fluorine on health 6 1.3- Significance of fluorine in natural products 8 1.3.1- Metabolites from plants 9 1.3.2- Metabolites from micro-organisms 10 1.4- Properties of fluorine 11 1.4.1- The fluorine atom 11 1.4.2- Physical properties of the C–F bond 12 1.4.3- Stereoelectronic properties of the C–F bond 13 1.4.3.1- Polarity 13 1.4.3.2- Bond strength 14 1.5- Fluorine in medicinal chemistry 15 1.5.1- Effects of fluorine on the properties of organic molecules 15 1.5.1.1- Perturbation of pKa 15 1.5.1.2- Modulation of lipophilicity 17 1.5.1.3- Steric and conformational changes 18 1.5.2- Metabolic stability 19 1.5.2.1- Oxidative mechanism 19 1.5.2.2- Hydrolytic metabolism 21 1.5.2.3- In vivo racemisation 22 1.5.3- Protein–Ligand interactions 23 1.5.3.1- Electrostatic interactions 23 1.5.3.2- Hydrogen bonding 24 1.5.4- Fluorine in nuclear medicine 26 1.6- Methods of fluorination 28 1.6.1- Nucleophilic reagents for fluorination 29 1.6.2- Electrophilic reagents for fluorination 34 1.6.3- Enantioselective monofluorination 35 1.6.3.1- Substrate control 35 1.6.3.2- Reagent control 36 1.6.3.3- Catalyst control 37 1.7-Conclusion 42 Chapter 2: α-Fluorinated capsaicins to alter the biological response of TRPV1 pain receptor 2.1- Introduction 47 2.2- TRPV1 receptor 53 2.2.1- Structure of TRPV1 54 2.2.2- Activation of the TRPV1 receptor 55 2.2.2.1- The critical residues for binding to TRPV1 56 2.2.2.2- The activation stimuli 58 2.2.3- Recent structural insights 59 2.3- Capsaicinoids 61 2.3.1- Structural elucidation of the capsaicinoids 61 2.3.2- Biosynthesis of capsaicin 62 2.4- Previous syntheses of capsaicin 64 2.4.1- Synthesis of vanillylamine 65 2.4.2- Syntheses of 8-methylnon-6-enoic acid 66 2.4.3- The Wittig approach 67 2.4.4- The Ortho-ester Claisen rearrangement 69 2.5- Aims and objectives 71 2.6- Results and discussion 75 2.6.1- Synthesis of (S)-fluorocapsaicin with Evans’oxazolidinone chiral auxiliary 75 2.6.1.1- Cross-metathesis (CM) strategy 75 2.6.1.2- Wittig strategy 84 2.6.1.3- Inverse Wittig route 85 2.6.1.4- Removal of the Evans auxiliary 89 2.6.1.5- Amide coupling to generate α-fluorocapsaicins 93 2.6.1.6- Route to dehydrocapsaicin 95 2.6.2- The use of imidazolidinones as organocatalyst for asymmetric α-fluorination 98 2.6.3- Analogues of capsaicin 101 2.6.3.1- Synthesis of shorter chain capsaicinoids analogues 101 2.6.3.2- Synthesis of the non-fluorinated short chain analogue 101 2.6.3.3- Deaminative fluorination 102 2.6.3.4- Asymmetric fluorination by organocatalysis 106 2.7- α,α-Difluorinated analogues 110 2.7.1- Theory study of α,α-difluoroamides 110 2.7.2- Synthesis of 2,2-difluoro-4-methylpentanoic acid 242 113 2.7.2.1- α,α-Difluorination by organocatalysis 113 2.7.2.2- α,α-Difluorination of α-ketoesters 114 2.7.3- Amide coupling of α,α-difluoro acid 115 2.7.4- α,α-Difluorination of α-ketoamides 117 2.8- Biological evaluation 118 2.8.1- Biological assay 119 2.8.1.1- Fluorinated enantiomers of capsaicin 119 2.8.1.2- Short fluorinated analogues of capsaicin 121 2.9- Conclusion 125 Chapter 3: Synthesis and organocatalysis from 2-(aminomethyl)piperidine 3.1- Diamines in medicinal chemistry and catalysis 131 3.1.1- The occurrence of vicinal diamines in natural products 132 3.1.2- Applications in medicinal chemistry 133 3.1.3- Vicinal diamines in synthesis 134 3.1.4- Preparation of vicinal diamines 137 3.2- Synthesis of enantiopure 2-(aminomethyl)piperidine 139 3.2.1- Previous syntheses of 2-(aminomethyl)piperidine 139 3.2.2- Précis 143 3.2.3- Enantioselective synthesis of 2-(aminomethyl)piperidine 144 3.2.3.1- Development of the cyclisation process 144 3.2.3.2- Hydrogenolysis of 318 and preparation of dihydrochloride 251 150 3.2.3.3- Preparation of 2-(aminomethyl)piperidine tetrafluoroborate salt 153 3.2.3.4- Enantiopurity and pKa analysis of dihydrochloride 251 154 3.3- Development of [4,4,0]-1,4-diazobicyclodecane 332 and its derivatives 157 3.4- 2-(Aminomethyl)piperidine as asymmetric organocatalyst 164 3.4.1- N-(Piperidin-2-ylmethyl)benzamide 362 165 3.4.2- 2,2,2-Trifluoro-N-(piperidin-2-ylmethyl)acetamide 363 167 3.4.3- 4-Methyl-N-(piperidin-2-ylmethyl)benzenesulfonamide 364 169 3.5- New catalyst for asymmetric Mannich reactions 175 3.5.1- Reactions catalysed by proline 175 3.5.2- Reaction with trifluoroacetamide organocatalyst 363 178 3.5.3- Reactions with organocatalyst 364 182 3.5.4- Mechanistic insights 184 3.6- Conclusion 186 Chapter 4: Experimental 4.1- General Methods 191 4.1.1- Reagents, solvents and reaction conditions 191 4.1.2- Chromatography and mass spectrometry 192 4.1.3- Nuclear magnetic resonance spectroscopy (NMR) 192 4.1.4- Other analysis 193 4.2- Protocols 194 4.3- Appendix 259 Abstract Chapter 1 gives an overview of the fluorine chemistry field, from its early developments to recent applications in medicinal chemistry.
Load more

Recommended publications
  • TRP Channel Transient Receptor Potential Channels
    TRP Channel Transient receptor potential channels TRP Channel (Transient receptor potential channel) is a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other. These are grouped into two broad groups: Group 1 includes TRPC ("C" for canonical), TRPV ("V" for vanilloid), TRPM ("M" for melastatin), TRPN, and TRPA. In group 2, there are TRPP ("P" for polycystic) and TRPML ("ML" for mucolipin). Many of these channels mediate a variety of sensations like the sensations of pain, hotness, warmth or coldness, different kinds of tastes, pressure, and vision. TRP channels are relatively non-selectively permeable to cations, including sodium, calcium and magnesium. TRP channels are initially discovered in trp-mutant strain of the fruit fly Drosophila. Later, TRP channels are found in vertebrates where they are ubiquitously expressed in many cell types and tissues. TRP channels are important for human health as mutations in at least four TRP channels underlie disease. www.MedChemExpress.com 1 TRP Channel Inhibitors, Antagonists, Agonists, Activators & Modulators (-)-Menthol (E)-Cardamonin Cat. No.: HY-75161 ((E)-Cardamomin; (E)-Alpinetin chalcone) Cat. No.: HY-N1378 (-)-Menthol is a key component of peppermint oil (E)-Cardamonin ((E)-Cardamomin) is a novel that binds and activates transient receptor antagonist of hTRPA1 cation channel with an IC50 potential melastatin 8 (TRPM8), a of 454 nM. Ca2+-permeable nonselective cation channel, to 2+ increase [Ca ]i. Antitumor activity. Purity: >98.0% Purity: 99.81% Clinical Data: Launched Clinical Data: No Development Reported Size: 10 mM × 1 mL, 500 mg, 1 g Size: 10 mM × 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg (Z)-Capsaicin 1,4-Cineole (Zucapsaicin; Civamide; cis-Capsaicin) Cat.
    [Show full text]
  • Determination of Capsaicinoid Profile of Some Peppers Sold in Nigerian Markets
    Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2014, 6(4):648-654 ISSN : 0975-7384 Research Article CODEN(USA) : JCPRC5 Determination of capsaicinoid profile of some peppers sold in Nigerian markets 1N. C. Nwokem *, 2C. O. Nwokem, 2Y. O. Usman, 1O. J. Ocholi, 2M. L. Batari and 3A. A. Osunlaja 1Department of Chemistry, Ahmadu Bello University, Zaria, Nigeria 2National Research Institute for Chemical Technology, Zaria, Nigeria 3Umar Suleiman College of Education, Gashua, Nigeria ____________________________________________________________________________________________ ABSTRACT The capsaicinoid profile of six different peppers sold in Nigerian markets was determined by Gas Chromatography- Mass Spectrometry. The capsaicinoids were extracted from the peppers using methanol as extractant and analyzed without need for derivatization. A total of eight (8) capsaicinoids were identified and quantitated: Capsaicin, Dihydrocapsaicin Dihydrocapsaicin 1, Dihydrocapsaicin 2, Norcapsaicin, Nordihydrocapsaicin 1, Nordihydrocapsaicin 2 and Nornordihydrocapsaicin though, not fully present in all the varieties. Dihydrocapsaicin 1, Dihydrocapsaicin 2, Nordihydrocapsaicin 1, Nordihydrocapsaicin 2 and Nornordihydrocapsaicin are isomers. Seven were identified in the Cameroun pepper variety, six in “Zaria atarugu” and Miango, and five in each of the remaining varieties. In all the peppers analyzed, capsaicin had the highest relative concentration, which ranged from 27.3% in the Cameroun variety to 49.38% in the “Zaria atarugu” variety. The sum of the relative concentrations of capsaicin and dihydrocapsaicin ranged from 47.03% in the “Miango” variety to 87.3% in the “Zaria atarugu” variety. Keywords: Capsaicinoids, Gas Chromatography-Mass Spectrometry, Methanol, Pepper ____________________________________________________________________________________________ INTRODUCTION Peppers are widely used in many parts of the world as a result of their valued sensory attributes; colour, purgency and aroma.
    [Show full text]
  • Determination of Capsaicinoids in Peppers by Microwave-Assisted Extraction–High-Performance Liquid Chromatography with fluorescence Detection Gerardo F
    Analytica Chimica Acta 578 (2006) 227–233 Determination of capsaicinoids in peppers by microwave-assisted extraction–high-performance liquid chromatography with fluorescence detection Gerardo F. Barbero, Miguel Palma ∗, Carmelo G. Barroso Grupo de Investigaci´on Qu´ımico Anal´ıtica del Vino y Productos Agroalimentarios, Departamento de Qu´ımica Analitica, Facultad de Ciencias, Universidad de C´adiz, Apartado 40, 11510 Puerto Real, C´adiz, Spain Received 30 March 2006; received in revised form 27 June 2006; accepted 28 June 2006 Available online 4 July 2006 Abstract A new method has been developed for the extraction of capsaicinoids (nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin) in peppers employing microwave-assisted extraction. The parameters studied are: extraction solvent (methanol, ethanol, acetone, ethyl acetate and water), temperature (50–200 ◦C), sample quantity (0.1–1 g), volume of solvent (15–50 mL) and the extraction time (5–20 min). The results found for the optimum conditions are: 125 ◦C as extraction temperature, 25 mL of solvent, 0.5 g of freshly triturated peppers and extraction for 5 min, employing 100% ethanol as solvent. The capsaicinoids obtained were stable under the optimised extraction conditions. The resulting method presents a high degree of reproducibility (R.S.D. < 6%). © 2006 Elsevier B.V. All rights reserved. Keywords: Microwave-assisted extraction; Capsaicinoids; Peppers 1. Introduction Many techniques for the extraction of capsaicinoids from peppers have been studied, such as maceration [9], magnetic stir- Hot or spicy peppers are savoury food additives that are ring [10], Soxhlet [11,12], ultrasound-assisted extraction [13], widely utilised in many parts of the world, and are highly valued extraction by means of supercritical fluids [14], extraction by for their attributes of colour, pungency, and aroma.
    [Show full text]
  • Historical Group
    Historical Group NEWSLETTER and SUMMARY OF PAPERS No. 64 Summer 2013 Registered Charity No. 207890 COMMITTEE Chairman: Prof A T Dronsfield | Prof J Betteridge (Twickenham, 4, Harpole Close, Swanwick, Derbyshire, | Middlesex) DE55 1EW | Dr N G Coley (Open University) [e-mail [email protected]] | Dr C J Cooksey (Watford, Secretary: Prof. J. W. Nicholson | Hertfordshire) School of Sport, Health and Applied Science, | Prof E Homburg (University of St Mary's University College, Waldegrave | Maastricht) Road, Twickenham, Middlesex, TW1 4SX | Prof F James (Royal Institution) [e-mail: [email protected]] | Dr D Leaback (Biolink Technology) Membership Prof W P Griffith | Dr P J T Morris (Science Museum) Secretary: Department of Chemistry, Imperial College, | Mr P N Reed (Steensbridge, South Kensington, London, SW7 2AZ | Herefordshire) [e-mail [email protected]] | Dr V Quirke (Oxford Brookes Treasurer: Dr J A Hudson | University) Graythwaite, Loweswater, Cockermouth, | Prof. H. Rzepa (Imperial College) Cumbria, CA13 0SU | Dr. A Sella (University College) [e-mail [email protected]] Newsletter Dr A Simmons Editor Epsom Lodge, La Grande Route de St Jean, St John, Jersey, JE3 4FL [e-mail [email protected]] Newsletter Dr G P Moss Production: School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS [e-mail [email protected]] http://www.chem.qmul.ac.uk/rschg/ http://www.rsc.org/membership/networking/interestgroups/historical/index.asp 1 RSC Historical Group Newsletter No. 64 Summer 2013 Contents From the Editor 2 Obituaries 3 Professor Colin Russell (1928-2013) Peter J.T.
    [Show full text]
  • Utilizing LC/UV and LC/MS for the Characterization, Isolation, And
    Utilizing LC/UV and LC/MS for the Characterization, Isolation, and Quantitation of Capsaicinoids in Chili Peppers and Hot Sauces J Preston, Seyed Sadjadi, Zeshan Aqeel, and Sky Countryman Phenomenex, Inc., 411 Madrid Ave., Torrance, CA 90501 USA PO19040114_W_2 PO14400613_W_2 Abstract Hot and spicy food has dramatically increased in popu- al different chili peppers and commercially available hot larity over the past 10-20 years. Capsaicin is the most sauces. Prep HPLC is then used to isolate individual cap- abundant compound found in chili peppers giving them saicinoids from the pepper extracts. Finally, a triple qua- their fiery flavor. Capsaicin is formed when vanillylamine druple MS system is employed to identify and quantitate is coupled to a 10 carbon fatty acid through an amide link- the observed capsaicinoids. age. However, there are other related compounds often called capsaicinoids. These compounds have the same Capsaicin was found to be the most prevalent capsaicinoid vanillylamine group but differ by the associated fatty acid species in all of the studied matrices. Significant amounts chain and are responsible for the perception of different of Nordihydrocapsaicin were found in a cayenne hot sauce heat profiles for different chili peppers. Some peppers are and in Thai chili pepper extract. Dihydrocapsaicin and Ho- described as having a high initial flash of heat while other modihydrocapsaicin were also identified in many of the in- peppers are described by a long and late burning profile. vestigated chili extracts and hot sauces but at lower levels. The typical concentration of these compounds were found The work presented here, initially uses HPLC with UV to be in the µg/g range but varied widely among the differ- detection to profile capsaicinoids extracted from sever- ent chili peppers and hot sauces.
    [Show full text]
  • Note: the Letters 'F' and 'T' Following the Locators Refers to Figures and Tables
    Index Note: The letters ‘f’ and ‘t’ following the locators refers to figures and tables cited in the text. A Acyl-lipid desaturas, 455 AA, see Arachidonic acid (AA) Adenophostin A, 71, 72t aa, see Amino acid (aa) Adenosine 5-diphosphoribose, 65, 789 AACOCF3, see Arachidonyl trifluoromethyl Adlea, 651 ketone (AACOCF3) ADP, 4t, 10, 155, 597, 598f, 599, 602, 669, α1A-adrenoceptor antagonist prazosin, 711t, 814–815, 890 553 ADPKD, see Autosomal dominant polycystic aa 723–928 fragment, 19 kidney disease (ADPKD) aa 839–873 fragment, 17, 19 ADPKD-causing mutations Aβ, see Amyloid β-peptide (Aβ) PKD1 ABC protein, see ATP-binding cassette protein L4224P, 17 (ABC transporter) R4227X, 17 Abeele, F. V., 715 TRPP2 Abbott Laboratories, 645 E837X, 17 ACA, see N-(p-amylcinnamoyl)anthranilic R742X, 17 acid (ACA) R807X, 17 Acetaldehyde, 68t, 69 R872X, 17 Acetic acid-induced nociceptive response, ADPR, see ADP-ribose (ADPR) 50 ADP-ribose (ADPR), 99, 112–113, 113f, Acetylcholine-secreting sympathetic neuron, 380–382, 464, 534–536, 535f, 179 537f, 538, 711t, 712–713, Acetylsalicylic acid, 49t, 55 717, 770, 784, 789, 816–820, Acrolein, 67t, 69, 867, 971–972 885 Acrosome reaction, 125, 130, 301, 325, β-Adrenergic agonists, 740 578, 881–882, 885, 888–889, α2 Adrenoreceptor, 49t, 55, 188 891–895 Adult polycystic kidney disease (ADPKD), Actinopterigy, 223 1023 Activation gate, 485–486 Aframomum daniellii (aframodial), 46t, 52 Leu681, amino acid residue, 485–486 Aframomum melegueta (Melegueta pepper), Tyr671, ion pathway, 486 45t, 51, 70 Acute myeloid leukaemia and myelodysplastic Agelenopsis aperta (American funnel web syndrome (AML/MDS), 949 spider), 48t, 54 Acylated phloroglucinol hyperforin, 71 Agonist-dependent vasorelaxation, 378 Acylation, 96 Ahern, G.
    [Show full text]
  • TRP CHANNELS AS THERAPEUTIC TARGETS TRP CHANNELS AS THERAPEUTIC TARGETS from Basic Science to Clinical Use
    TRP CHANNELS AS THERAPEUTIC TARGETS TRP CHANNELS AS THERAPEUTIC TARGETS From Basic Science to Clinical Use Edited by ARPAD SZALLASI MD, PHD Department of Pathology, Monmouth Medical Center, Long Branch, NJ, USA AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London, EC2Y 5AS, UK 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 225 Wyman Street, Waltham, MA 02451, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK First published 2015 Copyright © 2015 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangement with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein.
    [Show full text]
  • Capsicum Annum L.) in Southern USA
    ACTA AGRÍCOLA Y PECUARIA 6: E0061006 SCIENTIFIC ARTICLE https://doi.org/10.30973/aap/2020.6.0061006 (April 27, 2020) Effect of water stress on functional and marketable properties of roasted Big Jim chili pepper (Capsicum annum L.) in Southern USA Efecto del estrés hídrico en las propiedades funcionales y comerciales del chile rostizado Big Jim (Capsicum annum L.) en el sur de Estados Unidos Nancy Flores¹, Efrén Delgado¹, Stephanie Walker¹, Juan Rojas-Contreras², Gerardo Pámanes-Carrasco³* 1College of Agricultural, Consumer and Environmental Sciences, New Mexico State University, 1780 E University Ave, 88003, Las Cruces, New Mexico, United States of America. 2Instituto Tecnológico de Durango, Tecnológico Nacional de México, Boulevard Felipe Pescador #1830 Oriente, 34080, Durango, Durango, México. 3CONACYT-UJED, Instituto de Silvivultura e Industria de la Madera, Universidad Juárez del Estado de Durango, Boulevard Guadiana #501, Ciudad Universitaria, 34120, Durango, Durango, México. *Corresponding author: [email protected] Reception date: abstract January 19, 2020 This study aimed to evaluate the effect of water stress on spiciness, fatty acids, and aroma compound profile of roasted Big Jim chili. A flooded furrow irrigation system for chili Acceptance date: peppers production was utilized with 4 irrigation treatments: every 7, 9, 11, and 13 days March 18, 2020 for W1, W2, W3, and W4, respectively, in a completely randomized block design. Capsai- Online publication date: cinoid content was increased (~160%) by increasing water stress (P<0.05). However, the April 27, 2020 roasting process reduced the capsaicinoids content (P<0.05). Contents of linoleic, palmitic, and arachidonic acids were not affected. Water stress reduced hexanal and linalool content by approximately 64 and 72%, respectively (P<0.05), whereas 2-isobutyl-3-methoxypyrazi- ne content increased (P<0.05).
    [Show full text]
  • The Automated Flow Synthesis of Fluorine Containing Organic Compounds
    The automated flow synthesis of fluorine containing organic compounds by CHANTAL SCHOLTZ Submitted in partial fulfilment of the requirements for the degree PHILOSOPHAE DOCTOR In the Faculty of Natural & Agricultural Sciences UNIVERSITY OF PRETORIA PRETORIA Supervisor: Dr D.L. Riley February 2019 DECLARATION I, Chantal Scholtz declare that the thesis/dissertation, which I hereby submit for the degree PhD Chemistry at the University of Pretoria, is my own work and has not previously been submitted by me for a degree at this or any other tertiary institution. Signature :.......................................... Date :..................................... ii ACKNOWLEDGEMENTS I would herewith sincerely like to show my gratitude to the following individuals for their help, guidance and assistance throughout the duration of this project: My supervisor, Doctor Darren Riley, for his knowledge and commitment. Thank you for being a fantastic supervisor and allowing me the opportunity to learn so many valuable skills. My husband, Clinton, for all your love, support and patience and for always being there for me. You are the best. My family, for all the encouragement and support you gave me as well as always believing in me. I will always appreciate what you have done for me. Mr Drikus van der Westhuizen and Mr Johan Postma for their assistance at the Pelchem laboratories with product isolation and characterisation. Dr Mamoalosi Selepe for NMR spectroscopy services, Jeanette Strydom for XRF services and Gerda Ehlers at the UP library for her invaluable assistance. All my friends and colleagues for the continuous moral support, numerous helpful discussions and necessary coffee breaks. My colleagues at Chemical Process Technologies for their ongoing support and motivation, especially Dr Hannes Malan and Prof.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0053319 A1 Perry (43) Pub
    US 2009.0053319A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0053319 A1 Perry (43) Pub. Date: Feb. 26, 2009 (54) SORE THROAT RELIEF COMPOSITION AND Publication Classification METHOD OF PRODUCING SAME (51) Int. Cl. A6II 3/165. (2006.01) (76) Inventor: Wye Jeffrey Perry, Albany, NY A6IPA6II 35/64II/00 (2006.01) (52) U.S. Cl. .......................... 424/537; 514/625; 514/627 Correspondence Address: (57)57 ABSTRACT AMIN HALLIHAN, LLC The present invention provides a sore throat relief composi 444 NORTHORLEANS STREET, SUITE 400 tion and a method of producing the composition comprising CHICAGO, IL 60654 (US) oleoresin capsicum containing capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, and homocap saicin as active ingredients, combined with vegetable glyc (21) Appl. No.: 11/842,458 erin, purified water, spearmint oil, wild cherry bark, clove honey, and ascorbic acid for fully relieving and preventing chronic and occasional Sore throat symptoms, including pain, (22) Filed: Aug. 21, 2007 dryness, and inflammation. US 2009/00533 19 A1 Feb. 26, 2009 SORE THROAT RELEF COMPOSITION AND drocapsaicin is an irritant and has a similar pungency to METHOD OF PRODUCING SAME capsaicin. Nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicinare also irritants and have a pungency of about FIELD OF THE INVENTION 8,600,000-9,100,000 Scoville units. 0001. The present invention relates to a sore throat relief 0003. Each capsaicinoid and its corresponding chemical composition containing natural capsaicinoids for relieving structure is shown below. Capsaicin H O Dihydrocapsaicin O Nordihydrocapsaicin O Homodihydrocapsaicin O N O Homocapsaicin H O Sore throat pain, dryness, and inflammation along with pro 0004 Capsaicinoids are irritants and produce a sensation viding antimicrobial properties.
    [Show full text]
  • Fast Method for Capsaicinoids Analysis from Capsicum Chinense Fruits
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Food Research International 64 (2014) 718–725 Contents lists available at ScienceDirect Food Research International journal homepage: www.elsevier.com/locate/foodres Fast method for capsaicinoids analysis from Capsicum chinense fruits Marla Sganzerla a, Janclei Pereira Coutinho a, Arlete Marchi Tavares de Melo b, Helena Teixeira Godoy a,⁎ a Department of Food Science, Faculty of Food Engineering, University of Campinas (UNICAMP), P.O. Box 6121, 13083-862 Campinas, SP, Brazil b Horticultural Center, Agronomic Institute of Campinas (IAC), P.O. Box 28, 13012-970 Campinas, SP, Brazil article info abstract Article history: Chili peppers are widely utilized in the world as savory food additives due the pungency induced by the Received 28 January 2014 capsaicinoids. Also, these compounds have functional properties as antimutagenic, antitumoral, antioxidant Accepted 14 August 2014 and analgesic. These characteristics increase the interest in this compound class, hence the capsaicinoid analysis Available online 21 August 2014 must be reproducible and accurate. This study aimed to develop and validate a fast, efficient and reproducible method to analyze capsaicinoids in Brazilian Capsicum chinense fruits. The extracts were obtained after an opti- Keywords: Chili pepper mization step that indicated the condition 100% of methanol and 10 min on ultrasound assisted extraction. The Method development analyses were carried out in an ultra high performance liquid chromatographic system with detection by Ultrasound assisted extraction a photo diode array and mass spectrometer. The analytical method developed permits the separation of Ultra high performance liquid chromatography 8 capsaicinoids in 4 min of time analysis expending only 2 mL of solvent as mobile phase.
    [Show full text]
  • Things to Be Done
    DRAFT MAY 2003 ANNEX 1: CHEMICAL AGENTS 1. Introduction The large-scale use of toxic chemicals as weapons first became possible during the First World War (1914–1918) thanks to the growth of the chemical industry. More than 110 000 tonnes were disseminated over the battlefields, the greater part on the western front. Initially, the chemicals were used, not to cause casualties in the sense of putting enemy combatants out of action, but rather to harass. Though the sensory irritants used were powerful enough to disable those who were exposed to them, they served mainly to drive enemy combatants out of the trenches or other cover that protected them from conventional fire, or to disrupt enemy artillery or supplies. About 10% of the total tonnage of chemical warfare agents used during the war were chemicals of this type, namely lacrimators (tear gases), sternutators and vomiting agents. However, use of more lethal chemicals soon followed the introduction of disabling chemicals. In all, chemical agents caused some 1.3 million casualties, including 90 000 deaths. During the First World War, almost every known noxious chemical was screened for its potential as a weapon, and this process was repeated during the Second World War (1939–1945), when substantial stocks of chemical weapons were accumulated, although rarely used in military operations. Between the two world wars, a high proportion of all the new compounds that had been synthesized, or isolated from natural materials, were examined to determine their utility as lethal or disabling chemical weapons. After 1945, these systematic surveys continued, together with a search for novel agents based on advances in biochemistry, toxicology and pharmacology.
    [Show full text]