DOCSLIB.ORG

Synthesis of Insecticidal Mono- and Diacylhydrazines for Disruption of K+ Voltage-Gated Channels, Elucidation of Regiochemistry, And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthesis of Insecticidal Mono- and Diacylhydrazines for Disruption of K+ Voltage-Gated Channels, Elucidation of Regiochemistry, And Synthesis of Insecticidal Mono- and Diacylhydrazines for Disruption of K+ Voltage-Gated Channels, Elucidation of Regiochemistry, and Description of Conformational Isomerism by NMR Spectroscopy and Computation Joseph Shelby Clements II Dissertation submitted to the faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Chemistry Paul R. Carlier, Chair David G. I. Kingston James M. Tanko Gordon T. Yee May 2, 2017 Blacksburg, VA Keywords: Hydrazine, acylation, α-effect, regioselectivity, hydrazide, voltage- gated, (E)-/(Z)-, 19F NMR, single electron transfer (SET), rotational barrier, N-N bond rotation, rotational isomerism, helicity, transition state, dihedral angle Copyright 2017, Joseph S. Clements II Synthesis of Insecticidal Mono- and Diacylhydrazines for Disruption of K+ Voltage-Gated Channels, Elucidation of Regiochemistry, and Description of Conformational Isomerism by NMR Spectroscopy and Computation Joseph Shelby Clements II ABSTRACT Based on the success of diacyl-tert-butylhydrazines RH-5849 and RH-1266 in controlling agricultural crop pests, we endeavored to synthesize our own diacylbenzyl- and arylhydrazine derivatives for use against the malaria vector Anopheles gambiae. In the process of producing a library of compounds for assay against An. gambiae, it became clear that employing regioselective acylation techniques (in molecules that feature two nucleophilic, acyclic nitrogen atoms α to one another) would be imperative. Synthesis of the library derivatives proceeded rapidly and after topical assay, we found three compounds that were more toxic than the RH- series leads. One of the three displayed an LD50 value of half that of RH-1266, though patch clamp assay concluded that toxicity was not necessarily linked to inhibition of mosquito K+ channel Kv2.1. The acylation of monoarylhydrazines appears simple, but its regioselectivity is poorly understood when assumed as a function of basicity correlating to nucleophilic strength. We determined the ratio of the rate constants for distal to proximal N-acylation using 19F NMR spectroscopic analysis of reactions of 4-fluorophenylhydrazine with limiting (0.2 equiv) acylating agent in the presence of various bases. Acid anhydrides gave consistent preference for distal acylation. The selectivity of acylation by acyl chlorides when using pyridine gives strong distal preference, whereas use of triethylamine or aqueous base in conjunction with aroyl chlorides showed a moderate preference for proximal acylation. This observation yielded a convenient one-step method to synthesize proximal aroylarylhydrazines in yields comparable or superior to that provided by the standard three-step literature approach. Combined with NMR evidence of the distal nitrogen as the unambigiously stronger base of the two nitrogens, we propose a single electron transfer mechanism that predicts the regiochemistry of arylhydrazines toward acylating agents better than the nucleophilicity model based on pKa values. While synthesizing the acylhydrazine library for assay against An. gambiae, NMR spectroscopy revealed rotational isomerisms of two types: chiral helicity (M)/(P) and acyl (E)/(Z)-isomerism due to hindered rotation. Variable temperature NMR allowed the measurement of N-N bond rotational barriers, as well as estimate the barrier of (E)/(Z) interconversion. We obtained the X-ray crystal structures of four diacylhydrazines to test this hypothesis and revealed both the twist conformation around the N-N bond axis and (E)/(Z)- isomerism around the proximal acyl group. Computation (which agreed with the crystal structures) allowed us to estimate which (E)/(Z)-isomers were most likely being observed in solution at room temperature by NMR spectroscopy. In addition, we were able to calculate transition structures corresponding to N-N bond rotational barriers of (E,Z)- and (Z,Z)-isomers of model molecules and rationalize the difference in coalescence temperatures between (E,Z)- and (Z,Z)-isomers. GENERAL AUDIENCE ABSTRACT Herein we present the work of both synthesizing and characterizing the mosquitocidal and chemical properties of acylhydrazines. Part of the challenge of working with hydrazines comes in part from deceptive comparisons to amines and ammonia; hydrazine is as different from ammonia as hydrogen peroxide is from water. We were successful in identifying effective synthetic techniques to obtain our desired acylhydrazines reliably and managed to discover compounds that were better at eliminating Anopheles gambiae (the african malaria mosquito vector) than lead compounds from previous researchers. In the process of making the library of compounds for mosquito testing, we explored hydrazine reactivity toward acylating agents in a direct and deeper way than previous work, as well as their dynamic structural features. We employed a battery of techniques, including NMR, X-ray crystallography, and computational molecular modeling to understand these molecules and possibly contribute insight into their biochemical efficacy. Acknowledgements Firstly, I would like to extend my gratitude to my PhD advisor Dr. Paul R. Carlier. More than once, we would sit down for a 30 minute meeting about some results from the past week and 2 hours later we would have come up with a new idea to test. My work with Paul Carlier has always been mutual collaboration with emphasis on discovery and clarity. He has shown receptiveness to my ideas and independent thinking; all the while, not being afraid to tell me when I’m wrong...and sometimes vice versa. As we transition from the relationship of the student and the teacher to becoming colleagues, I will still look toward Dr. Carlier for his professional advice and counsel. It has been a pleasure to work with him over these past several years. I would also like to thank my advisory committee Drs. Kingston, Tanko, and Yee for their suggestions, patience, and interest in my work and my professional success. Secondly, I would like to thank my fellow graduate students, post-doctoral colleagues, collaborators, and analytical staff for their willingness to work with me to achieve success in my research work. I’d like to thank Drs. Qiao-Hong Chen and Ming Ma for their indispensable and practical guidance at the very beginning of my graduate career in organic synthesis. I’d like to thank Drs. Dinesh Nath and Zhong-Ke Yao for working alongside me on acylhydrazine syntheses at the beginning of that project, as well as my former pupil Michael Black. I thank Dr. Eric Nybo for our long friendship and conversations on our research which has proved inspiring time after time. I extend my gratitude to Dr. Gary Richoux, Dr. Astha Verma, Dr. Eugene Camerino, Dr. Neeraj Patwardhan, Sha Ding, and Lixuan Liu for your time and inclination to discuss my work and offer your thoughts. Maryam Ghavami deserves special thanks for contributing her synthetic prowess to my project on regioselective proximal acylation of aryl hydrazines. I am grateful to Dr. Carla Slebodnick for her expertise and advice toward obtaining v the vital X-ray crystal structures for my research. My sincere gratitude goes to Dr. Narasimhamurthy Shanaiah and Ken Knott for their guidance and hours of time in front of the 600 MHz NMR, helping me learn how to do variable temperature measurements properly. I’d like to thank Bill Bebout and Dr. Mehdi Ashraf-Khorassani for their hard work, troubleshooting, and patience with me and my compounds. I’d like to thank our collaborators Drs. Jeff Bloomquist, Fan Tong, Rafique Islam, and Baonan Sun at the University of Florida Department of Entomology and Nematology for their diligent work in biological assay of my compound library for mosquito toxicity as well as K+ channel inhibition. Finally, those outside of academia have contributed greatly to my success and they too deserve recognition for their part this accomplishment. My parents, Markus and Sharon Clements deserve thanks for their love, their moral and material support, and allowing me to pursue science and encouraging it at a young age. I thank my sister Kristi Wilkinson for her support and protectiveness of her little brother in his vulnerable young years. My Mother and Father in-law, David and Peggy Heimerdinger supported me when I needed it and I will remember it always. Lastly, I would like to thank my wife Rachel Kathryn Heimerdinger most of all. You were there for me when I was at my weakest in mind and body; it was your love, work, patience, courage, and fortitude that have seen me through to this moment and I am forever grateful. vi Dedication I dedicate this work to Rachel Kathryn Heimerdinger and all those who would pursue and facilitate scientific endeavor for the furtherance of our human civilization. vii Chapter 1. Introduction to Hydrazine Chemistry: Nucleophilicity, Synthesis, Conformational Chirality and Isomerism .................................................................................. 1 1.1 Introduction ........................................................................................................................... 1 1.2 Insecticidal action of diacylhydrazines ................................................................................. 5 1.3 The α-effect ........................................................................................................................... 9 1.4 Direct alkylation of phenylhydrazine by alkylhalides. ....................................................... 17 1.5 Acylation
Load more

Recommended publications
  • Monoamine Oxydases Et Athérosclérose : Signalisation Mitogène Et Études in Vivo
    UNIVERSITE TOULOUSE III - PAUL SABATIER Sciences THESE Pour obtenir le grade de DOCTEUR DE L’UNIVERSITE TOULOUSE III Discipline : Innovation Pharmacologique Présentée et soutenue par : Christelle Coatrieux le 08 octobre 2007 Monoamine oxydases et athérosclérose : signalisation mitogène et études in vivo Jury Monsieur Luc Rochette Rapporteur Professeur, Université de Bourgogne, Dijon Monsieur Ramaroson Andriantsitohaina Rapporteur Directeur de Recherche, INSERM, Angers Monsieur Philippe Valet Président Professeur, Université Paul Sabatier, Toulouse III Madame Nathalie Augé Examinateur Chargé de Recherche, INSERM Monsieur Angelo Parini Directeur de Thèse Professeur, Université Paul Sabatier, Toulouse III INSERM, U858, équipes 6/10, Institut Louis Bugnard, CHU Rangueil, Toulouse Résumé Les espèces réactives de l’oxygène (EROs) sont impliquées dans l’activation de nombreuses voies de signalisation cellulaires, conduisant à différentes réponses comme la prolifération. Les EROs, à cause du stress oxydant qu’elles génèrent, sont impliquées dans de nombreuses pathologies, notamment l’athérosclérose. Les monoamine oxydases (MAOs) sont deux flavoenzymes responsables de la dégradation des catécholamines et des amines biogènes comme la sérotonine ; elles sont une source importante d’EROs. Il a été montré qu’elles peuvent être impliquées dans la prolifération cellulaire ou l’apoptose du fait du stress oxydant qu’elles génèrent. Ce travail de thèse a montré que la MAO-A, en dégradant son substrat (sérotonine ou tyramine), active une voie de signalisation mitogène particulière : la voie métalloprotéase- 2/sphingolipides (MMP2/sphingolipides), et contribue à la prolifération de cellules musculaire lisses vasculaires induite par ces monoamines. De plus, une étude complémentaire a confirmé l’importance des EROs comme stimulus mitogène (utilisation de peroxyde d’hydrogène exogène), et a décrit plus spécifiquement les étapes en amont de l’activation de MMP2, ainsi que l’activation par la MMP2 de la sphingomyélinase neutre (première enzyme de la cascade des sphingolipides).
    [Show full text]
  • Transport of Dangerous Goods
    ST/SG/AC.10/1/Rev.16 (Vol.I) Recommendations on the TRANSPORT OF DANGEROUS GOODS Model Regulations Volume I Sixteenth revised edition UNITED NATIONS New York and Geneva, 2009 NOTE 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 Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. ST/SG/AC.10/1/Rev.16 (Vol.I) Copyright © United Nations, 2009 All rights reserved. No part of this publication may, for sales purposes, be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical, photocopying or otherwise, without prior permission in writing from the United Nations. UNITED NATIONS Sales No. E.09.VIII.2 ISBN 978-92-1-139136-7 (complete set of two volumes) ISSN 1014-5753 Volumes I and II not to be sold separately FOREWORD The Recommendations on the Transport of Dangerous Goods are addressed to governments and to the international organizations concerned with safety in the transport of dangerous goods. The first version, prepared by the United Nations Economic and Social Council's Committee of Experts on the Transport of Dangerous Goods, was published in 1956 (ST/ECA/43-E/CN.2/170). In response to developments in technology and the changing needs of users, they have been regularly amended and updated at succeeding sessions of the Committee of Experts pursuant to Resolution 645 G (XXIII) of 26 April 1957 of the Economic and Social Council and subsequent resolutions.
    [Show full text]
  • June 2009 MONTHLY MEETING : PLEASE PAY YOUR DUES: WHEN? Monday, June 22, 2009 – the Fourth Monday of in Accordance with the By-Laws, Dues, in the the Month
    Spore-Addct The Newsletter of the Pikes PeakTime Mycological Society 1974 – 2009 Vol. XXXV ISSUE 3 June 2009 MONTHLY MEETING : PLEASE PAY YOUR DUES: WHEN? Monday, June 22, 2009 – The fourth Monday of In accordance with the By-laws, dues, in the the month. amount of $15.00, are due and payable on or before the April monthly meeting. If you still WHAT TIME? 6:30 pm; the meeting will come to order at have not paid, please pay at the June meeting or 7:00 pm. mail the payment to PPMS, PO Box 39, Colorado Springs, CO 80901-0039. Thanks! WHERE? Pikes Peak National Bank, 2401 W. Colorado Ave. (across from Bancroft Park). Enter at the door on Colorado Ave., just west of the bank door. There you will find stairs and an elevator. You may use either. The FORAY REPORT: room is on the second floor near the head of the stairs. May 30th 2009: Ten of us (including 2 newcomers to WEBSITE: http://www.pikespeakmushrooms.com/ PPMS) gathered at the Red Rocks Safeway parking lot at 8:30 a.m. All had either been contacted by e-mail or PROGRAM: personal phone call. All club forays will be scheduled like this. Our eager forayers found only 6 small morels, A NAMA Educational Program: 2 L.B.Ms, and some dubious polypors. We did come “Guide to the Major Genera of Gilled Mushrooms: The across 6 Calypso orchids (unaccompanied by morels). Light Spored Mushrooms I: Pluteaceae, Pleurotaceae, It was a beautiful day on Rampart Range Road. Rain Entolomataceae, Marasmiaceae and Others” and warmer temperatures have brought out city This program covers the best edible and most mushrooms galore.
    [Show full text]
  • Screening of Potentially Genotoxic Impurities in Pharmaceuticals by LC-MS and CE-MS
    Screening of potentially genotoxic impurities in pharmaceuticals by LC-MS and CE-MS Screening van potentieel genotoxische onzuiverheden in farmaceutische producten met LC-MS en CE-MS (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof. dr. G.J. van der Zwaan, ingevolge van het besluit van het college voor promoties in het openbaar te verdedigen op maandag 21 november 2016 des middags te 2.30 uur. door Anthonius Maria van Wijk geboren op 3 juli 1968 te Oostflakkee Promotor: Prof. dr. G.J. de Jong Copromotor: Dr. H.A.G. Niederländer Index Chapter 1 Introduction 5 Chapter 2 The potential for screening of potentially genotoxic impurities 19 in pharmaceutical products Chapter 3 A new approach for generic screening and quantitation of 71 potential genotoxic alkylation compounds by pre-column derivatization and LC-MS/MS analysis Chapter 4 A new derivatization reagent for LC–MS/MS screening of 91 potential genotoxic alkylation compounds Chapter 5 Capillary electrophoresis – mass spectrometry for impurity 115 profiling of basic pharmaceuticals using non-volatile background electrolytes Chapter 6 Sensitive CE-MS analysis of potentially genotoxic alkylation 137 compounds using derivatization and electrokinetic injection Chapter 7 Summary and general conclusions 159 Summary in Dutch/Nederlandse samenvatting 174 Curriculum Vitae 182 List of publications 183 Acknowledgements/Dankwoord 184 Chapter 1 Introduction 5 Chapter 1 1.1 Control of genotoxic impurities Trace analysis of potential genotoxic impurities (PGIs) is one of the greatest challenges in pharmaceutical analysis. Traces of toxic impurities, i.e.
    [Show full text]
  • Silybum Marianum (Milk Thistle) Flower in Vitro and on Human Explants
    Molecules 2015, 20, 3549-3564; doi:10.3390/molecules20033549 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Anti-Glycation Activities of Phenolic Constituents from Silybum marianum (Milk Thistle) Flower in Vitro and on Human Explants Seoungwoo Shin, Jung-A Lee, Minkyung Kim, Hyunwoo Kum, Eunsun Jung * and Deokhoon Park * Biospectrum Life Science Institute, Eines Platz 11th FL, 442-13 Sangdaewon Dong, Seoungnam City, Gyunggi Do 462-807, Korea; E-Mails: [email protected] (S.S.); [email protected] (J.-A.L.); [email protected] (M.K.); [email protected] (H.K.) * Authors to whom correspondence should be addressed; E-Mails: [email protected] (E.J.); [email protected] (D.P.); Tel.: +82-31-750-9400 (E.J. & D.P.); Fax: +82-31-750-9494 (E.J. & D.P.). Academic Editor: Derek J. McPhee Received: 25 November 2014 / Accepted: 15 February 2015 / Published: 19 February 2015 Abstract: Glycation is an ageing reaction of naturally occurring sugars with dermal proteins, with clinical signs appearing in vivo around age 30, and increasing steadily/regularly with age. The suppleness of the dermis is affected by the formation of bridges between proteins and sugars (Maillard’s reaction). The accumulation of advanced glycation end products (AGEs) in skin plays a very important role in skin ageing. Therefore, natural compounds or extracts that possess antiglycation activities may have great anti-ageing potential. In the present study, Silybum marianum flower extract (SMFE) was demonstrated to possess antiglycation activity. We found that SMFE inhibits glycation reaction between BSA and glucose. In addition, antiglycation activity of SMFE was confirmed in a human skin explants model.
    [Show full text]
  • Toxicological Profile for Hydrazines. US Department Of
    TOXICOLOGICAL PROFILE FOR HYDRAZINES U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry September 1997 HYDRAZINES ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. HYDRAZINES iii UPDATE STATEMENT Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE, E-29 Atlanta, Georgia 30333 HYDRAZINES vii CONTRIBUTORS CHEMICAL MANAGER(S)/AUTHOR(S): Gangadhar Choudhary, Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Hugh IIansen, Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Steve Donkin, Ph.D. Sciences International, Inc., Alexandria, VA Mr. Christopher Kirman Life Systems, Inc., Cleveland, OH THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 1 . Green Border Review. Green Border review assures the consistency with ATSDR policy. 2 . Health Effects Review. The Health Effects Review Committee examines the health effects chapter of each profile for consistency and accuracy in interpreting health effects and classifying end points. 3. Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to substance-specific minimal risk levels (MRLs), reviews the health effects database of each profile, and makes recommendations for derivation of MRLs. HYDRAZINES ix PEER REVIEW A peer review panel was assembled for hydrazines. The panel consisted of the following members: 1. Dr.
    [Show full text]
  • Synthetic and Naturally Occurring Hydrazines As Possible Cancer Causative Agents
    [CANCER RESEARCH 35, 3693-3697 December 1975] Synthetic and Naturally Occurring Hydrazines as Possible Cancer Causative Agents Bela Toth' The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68105 SUMMARY SYNTHETIC HYDRAZINES The various synthetic substituted hydrazines, which cause tumors in animals, are briefly enumerated. To date, 19 of Studies on the carcinogenic potentialities of synthetic them have proved to be tumorigenic in animals. A number substituted hydrazines began in 1962, when it was shown of these chemicals are found today in the environment, in that the base compound hydrazine sulfate induced lung industry, in agriculture, and in medicine, and the human neoplasms in mice (1). Subsequently, a series of hydrazine population is exposed to a certain degree to some of them. derivatives were investigated in various laboratories for Hydrazine also occurs in nature in tobacco and tobacco tumor-inducing capabilities. These studies clearly demon smoke. The three other naturally occurring hydrazine strated that these chemicals are indeed powerful tumori compounds are N-methyl-N-formylhydrazine, which oc genic substances in mice, hamsters, and rats, due to their curs in the wild edible mushroom, Gyromitra esculenta, tumor-inducing abilities in the intestines, brain, lungs, and @-N-[―y-L(+)-glutamylJ-4-hydroxymethylphenyl blood vessels, liver, breasts, kidneys, etc. Now, we know of hydrazine and 4-hydroxymethylphenylhydrazine, whkh 19 hydrazine derivatives that have been shown to be tumor are found in the commonly eaten cultivated mushroom, inducers. These include, in addition to hydrazine (1, 32), Agaricus bisporus. Tumorigenesis studies with the natu methyl- (35, 40), 1,2-dimethyl- (6, 27, 36, 46, 52), 1,1- rally occurring hydrazines are in progress.
    [Show full text]
  • Hydrazine 1 Hydrazine
    Hydrazine 1 Hydrazine Hydrazine Identifiers [1] CAS number 302-01-2 , 7803-57-8 (hydrate) [2] EC number 206-114-9 UN number 2029 (anhydrous) 2030 (aq. soln., 37–64%) 3293 (aq. soln., <37%) RTECS number MU7175000 Properties Molecular formula N H 2 4 Molar mass 32.05 g/mol (anhydrous) 50.06 g/mol (hydrate) Appearance Colourless liquid Density 1.0045 g/cm3 (anhydrous) 1.032 g/cm3 (hydrate) Melting point 1 °C (274 K, anhydrous) -51.7 °C (hydrate) Boiling point 114 °C (387 K), anhydrous 119 °C (hydrate) Solubility in water miscible Acidity (pK ) 8.1 a Refractive index (n ) [3] D 1.46044 (22 °C, anhydrous) 1.4284 (hydrate) Viscosity 0.876 cP (25 °C) Structure Hydrazine 2 Molecular shape pyramidal at N [4] Dipole moment 1.85 D Hazards [5] MSDS ICSC 0281 EU Index 007-008-00-3 EU classification Carc. Cat. 2 Toxic (T) Corrosive (C) Dangerous for the environment (N) R-phrases R45, R10, R23/24/25, R34, R43, R50/53 S-phrases S53, S45, S60, S61 NFPA 704 Flash point 52 °C Autoignition 24–270 °C (see text) temperature Explosive limits 1.8–100% LD [6] 50 59–60 mg/kg (oral in rats, mice) Related compounds Related nitrogen hydrides Ammonia Hydrazoic acid Related compounds monomethylhydrazine dimethylhydrazine phenylhydrazine [7] (what is this?) (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox references Hydrazine is an inorganic chemical compound with the formula N H . It is a colourless liquid with an 2 4 ammonia-like odor and is derived from the same industrial chemistry processes that manufacture ammonia.
    [Show full text]
  • SOMA NEWS EDITOR Tom Cruckshank [email protected] Meet at Woodside Campground in Salt Point State Park at 10 AM
    VOLUME 22 ISSUE 1 September 2009 SOMA IS AN EDUCATIONAL ORGANIZATION DEDICATED TO MYCOLOGY. WE ENCOURAGE ENVIRONMENTAL AWARENESS BY SHARING OUR ENTHUSIASM THROUGH PUBLIC PARTICIPATION AND GUIDED FORAYS. 2009/2010 SPEAKER OF THE MONTH SEASON CALENDAR David Campbell September Sept. 17th » Meeting—7pm September 17th—7pm—Farm Bureau Sonoma County Farm Bureau Speaker: David Campbell Rocky Monsoon Mushrooms: Foray Sept. 19th » Salt Point A peek at summer fungi of southwestern Colorado October avid Campbell… has been collecting, studying, eating, teaching and writing about Oct. 15th » Meeting—7pm D wild mushrooms for 40 years. He has served many years on the council of the Sonoma County Farm Bureau Mycological Society of San Francisco (MSSF), including 2 years as president. For many Speaker: Don Hemmes years, David has served the San Francisco Poison Control Center for mushroom poisoning incident response in Marin County and the greater Bay Area. With a primary Foray Oct. 17th » Salt Point focus on edible and poisonous mushrooms, he leads innumerable fungal forays for November MSSF and the Sonoma Mycological Association (SOMA). David was foray leader and event facilitator for several years at author David Arora's annual mycological field Nov. 20th » Meeting—7pm seminars. As an expert mycophagist (one who safely eats a wide variety of wild Sonoma County Farm Bureau mushrooms) and experienced outdoor group foray leader, David is ‘Foray Director’ for Speaker: TBA Wild About Mushrooms Company, guiding organized wild mushroom adventures, locally Foray Nov. 21st » Salt Point and afar. He recently formed his own company, MycoVentures, Inc., expanding his horizons to include the rest of the planet, for events such as Porcini hunts in the December Potluck on the 11th.
    [Show full text]
  • (10) Patent No.: US 8119385 B2
    US008119385B2 (12) United States Patent (10) Patent No.: US 8,119,385 B2 Mathur et al. (45) Date of Patent: Feb. 21, 2012 (54) NUCLEICACIDS AND PROTEINS AND (52) U.S. Cl. ........................................ 435/212:530/350 METHODS FOR MAKING AND USING THEMI (58) Field of Classification Search ........................ None (75) Inventors: Eric J. Mathur, San Diego, CA (US); See application file for complete search history. Cathy Chang, San Diego, CA (US) (56) References Cited (73) Assignee: BP Corporation North America Inc., Houston, TX (US) OTHER PUBLICATIONS c Mount, Bioinformatics, Cold Spring Harbor Press, Cold Spring Har (*) Notice: Subject to any disclaimer, the term of this bor New York, 2001, pp. 382-393.* patent is extended or adjusted under 35 Spencer et al., “Whole-Genome Sequence Variation among Multiple U.S.C. 154(b) by 689 days. Isolates of Pseudomonas aeruginosa” J. Bacteriol. (2003) 185: 1316 1325. (21) Appl. No.: 11/817,403 Database Sequence GenBank Accession No. BZ569932 Dec. 17. 1-1. 2002. (22) PCT Fled: Mar. 3, 2006 Omiecinski et al., “Epoxide Hydrolase-Polymorphism and role in (86). PCT No.: PCT/US2OO6/OOT642 toxicology” Toxicol. Lett. (2000) 1.12: 365-370. S371 (c)(1), * cited by examiner (2), (4) Date: May 7, 2008 Primary Examiner — James Martinell (87) PCT Pub. No.: WO2006/096527 (74) Attorney, Agent, or Firm — Kalim S. Fuzail PCT Pub. Date: Sep. 14, 2006 (57) ABSTRACT (65) Prior Publication Data The invention provides polypeptides, including enzymes, structural proteins and binding proteins, polynucleotides US 201O/OO11456A1 Jan. 14, 2010 encoding these polypeptides, and methods of making and using these polynucleotides and polypeptides.
    [Show full text]
  • Production of Malonic Acid Through the Fermentation of Glucose
    University of Pennsylvania ScholarlyCommons Department of Chemical & Biomolecular Senior Design Reports (CBE) Engineering 4-20-2018 Production of Malonic Acid through the Fermentation of Glucose Emily P. Peters University of Pennsylvania, [email protected] Gabrielle J. Schlakman University of Pennsylvania, [email protected] Elise N. Yang University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/cbe_sdr Part of the Biochemical and Biomolecular Engineering Commons Peters, Emily P.; Schlakman, Gabrielle J.; and Yang, Elise N., "Production of Malonic Acid through the Fermentation of Glucose" (2018). Senior Design Reports (CBE). 107. https://repository.upenn.edu/cbe_sdr/107 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/cbe_sdr/107 For more information, please contact [email protected]. Production of Malonic Acid through the Fermentation of Glucose Abstract The overall process to produce malonic acid has not drastically changed in the past 50 years. The current process is damaging to the environment and costly, requiring high market prices. Lygos, Inc., a lab in Berkeley, California, has published a patent describing a way to produce malonic acid through the biological fermentation of genetically modified easty cells. This proposed technology is appealing as it is both better for the environment and economically friendly. For the process discussed in this report, genetically modified Pichia Kudriavzevii yeast cells will be purchased from the Lygos lab along with the negotiation of exclusive licensing rights to the technology. The cells will be grown in fermentation vessels, while being constantly fed oxygen, glucose and fermentation media. The cells will excrete malonic acid in the 101 hour fermentation process.
    [Show full text]
  • Preparation of Amine Alanes
    Europaisches Patentamt J European Patent Office 00 Publication number: 0 273 229 Office europeen des brevets A2 EUROPEAN PATENT APPLICATION © Application number: 87117901.6 © mt. ci.<: C01B 6/06 , C07C 87/00 © Date of filing: 03.12.87 © Priority: 22.12.86 US 945286 © Applicant: ETHYL CORPORATION Ethyl Tower 451 Florida Boulevard ® Date of publication of application: Baton Rouge Louisiana 70801 (US) 06.07.88 Bulletin 88/27 @ Inventor: Marlett, Everett Michael ® Designated Contracting States: 9355 Greenbriar Drive AT BE CH DE ES FR GB IT LI LU NL SE Baton Rouge Louisiana 7081 5(US) 0 Representative: Sandmair, Kurt, Dr. Patentanwalte Schwabe, Sandmair, Marx Stuntzstrasse 16 D-8000 MUnchen 80(DE) © Preparation of amine alanes. © Process for the preparation of an amine alane, said process comprising reacting: (a) an alkali metal aluminum tetrahydride having the formula MAIH4, wherein M is an alkali metal selected from the class consisting of lithium, sodium and potassium, (b) a hydrogen halide, and (c) a complexing tertiary amine. In this process, NaAlhU, HCI, and (C2H5)3N are preferred reactants. CM CM a. LU Xerox Copy Centre 0 273 229 PREPARATION OF AM1NE ALANES The invention pertains to the formation of amine alanes AIH3«NR3. These materials are useful as chemical intermediates. For example, they can be reacted with a silicon halide such as SiCU or SiF4 to produce silane. Reference is made to U.S. 4,474,743. It pertains to production of silane and aluminum fluoride from silicon tetrafluoride and amine alanes. Reference is also made to U.S. 4,006,095. It teaches, inter alia, that SiCU reacts with a toluene solution of AIH3 containing dimethyl ether or a stabilizing amine.
    [Show full text]