Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis "227
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Enantioselective Synthesis of Bioactive Molecules Via
ENANTIOSELECTIVE SYNTHESIS OF BIOACTIVE MOLECULES VIA ASYMMETRIC HYDROXYLATIONS, AMINOALLYLATION AND SYNTHETIC METHODOLOGIES INVOLVING ACTIVATION OF C-H BONDS A THESIS SUBMITTED TO THE UNIVERSITY OF PUNE FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN CHEMISTRY By TANVEER MAHAMADALI SHAIKH UNDER THE GUIDANCE Dr. A. Sudalai Chemical Engineering and Process Development Division National Chemical Laboratory Pune-411008, INDIA November 2009 Dedicated to my beloved parents & brother Raziya Mahamadali & Sameer NATIONAL CHEMICAL LABOATORY Dr. A. Sudalai Scientist Chemical Engineering & Process Development Division, Pune – 411 008, India Phone (O) : 0091-20-25902174, Fax: 0091-20-25902676, e-mail: [email protected] CERTIFICATE Certified that the work incorporated in the thesis entitled “Enantioselective Synthesis of Bioactive Molecules via Asymmetric Hydroxylations, Aminoallylation and Synthetic Methodologies Involving Activation of C-H Bonds” was carried out by the candidate under my supervision. Such material as had been obtained from other sources has been duly acknowledged in the thesis. November 2009 (Dr. A. Sudalai) Pune Research Supervisor NATIONAL CHEMICAL LABORATORY DECLARATION I here by declare that the thesis entitled “Enantioselective Synthesis of Bioactive Molecules via Asymmetric Hydroxylations, Aminoallylation and Synthetic Methodologies Involving Activation of C-H Bonds” submitted for the degree of Doctor of Philosophy in Chemistry to the University of Pune, has not been submitted by me to any other university or institution. This -
SYNTHESIS Journal Of
Journal of Synthetic Organic SYNTHESIS Chemistry REPRINT With compliments of the Author Thieme SHORT REVIEW ▌2551 short review Conhydrine: An Account of Isolation, Biological Perspectives and Synthesis l ChinmayConhydrine: A Short Review Bhat,*a Sandesh T. Bugde,b Santosh G. Tilve*b a Centre for Nano and Material Sciences, Jain Global Campus, Jakkasandara Post, Kanakapura Road, Ramanagara District, Karnataka 562 112, India b Department of Chemistry, Goa University, Taleigao Plateau, Goa 403 206, India Fax +91(832)6519317; Fax +91(965)7962641; E-mail: [email protected]; E-mail: [email protected] Received: 23.05.2014; Accepted after revision: 06.08.2014 Abstract: Conhydrine is a naturally occurring 2-substituted piperi- dine alkaloid from the plant Conium maculatum L that exists in four different forms and is known for its high toxicity. This article focus- es on the synthesis of conhydrine as its medicinal applications are limited due to its high toxicity. The various asymmetric methods de- veloped for the synthesis of conhydrine are classified based on the methodology: the chiral pool method, the chiral auixiliary method, and asymmetric catalysis. A brief overview of the complete synthet- ic coverage of conhydrine (1948–2014) in different isomeric forms is given. Dr. Chinmay Bhat was born in Sirsi, Karnataka, India. He moved to 1 Introduction the Department of Chemistry, Goa University in 2006 for his M.Sc. 2 Isolation and Biological Perspectives in chemistry. After qualifying CSIR-NET-JRF in 2007, he joined the 3 Synthesis group of Prof. Santosh Tilve in 2008 in the doctoral programme and 3.1 Chiral Pool Methods worked on the asymmetric synthesis of natural products. -
Solanum Alkaloids and Their Pharmaceutical Roles: a Review
Journal of Analytical & Pharmaceutical Research Solanum Alkaloids and their Pharmaceutical Roles: A Review Abstract Review Article The genus Solanum is treated to be one of the hypergenus among the flowering epithets. The genus is well represented in the tropical and warmer temperate Volume 3 Issue 6 - 2016 families and is comprised of about 1500 species with at least 5000 published Solanum species are endemic to the northeastern region. 1Department of Botany, India Many Solanum species are widely used in popular medicine or as vegetables. The 2Department of Botany, Trivandrum University College, India presenceregions. About of the 20 steroidal of these alkaloid solasodine, which is potentially an important starting material for the synthesis of steroid hormones, is characteristic of *Corresponding author: Murugan K, Plant Biochemistry the genus Solanum. Soladodine, and its glocosylated forms like solamargine, and Molecular Biology Lab, Department of Botany, solosonine and other compounds of potential therapeutic values. India, Email: Keywords: Solanum; Steroidal alkaloid; Solasodine; Hypergenus; Glocosylated; Trivandrum University College, Trivandrum 695 034, Kerala, Injuries; Infections Received: | Published: October 21, 2016 December 15, 2016 Abbreviations: TGA: Total Glycoalkaloid; SGA: Steroidal range of biological activities such as antimicrobial, antirheumatics, Glycoalkaloid; SGT: Sergeant; HMG: Hydroxy Methylglutaryl; LDL: Low Density Lipoprotein; ACAT: Assistive Context Aware Further, these alkaloids are of paramount importance in drug Toolkit; HMDM: Human Monocyte Derived Macrophage; industriesanticonvulsants, as they anti-inflammatory, serve as precursors antioxidant or lead molecules and anticancer. for the synthesis of many of the steroidal drugs which have been used CE: Cholesterol Ester; CCl4: Carbon Tetrachloride; 6-OHDA: 6-hydroxydopamine; IL: Interleukin; TNF: Tumor Necrosis Factor; DPPH: Diphenyl-2-Picryl Hydrazyl; FRAP: Fluorescence treatments. -
Ethno-Botanic Treatments for Paralysis (Falij) in the Middle East
Chinese Medicine, 2012, 3, 157-166 http://dx.doi.org/10.4236/cm.2012.34025 Published Online December 2012 (http://www.SciRP.org/journal/cm) Ethno-Botanic Treatments for Paralysis (Falij) in the Middle East Aref Abu-Rabia Ben-Gurion University of the Negev, Beer-Sheva, Israel Email: [email protected] Received April 12, 2012; revised July 24, 2012; accepted August 9, 2012 ABSTRACT The goal of this paper is to describe beliefs and treatments for specific forms of Paralysis (falij) and other nervous dis- orders in the Middle East. Themes to be investigated include, the traditional medicinal practices used to treat Paralysis, as well as their curative methods using traditional herbal medicine. This paper is based on first and secondary sources; interviews with traditional healers, as well as patients who suffered from these disorders. The author found 152 plants species belonging to 58 families (see Appendix) that treat paralysis and other nervous disorders. The most significant plants species are found in the six families of herbs: Labiatae, Compositae, Umbelliferae, Papilionaceae, Liliaceae, and Solanaceae. Keywords: Paralysis; Ethno Botanic Medicine; Middle East 1. Introduction peak in the thirteenth through sixteenth centuries, and later declined during the seventeenth through the nine- The use of plant medicines in the Middle East has his- teenth centuries. Medical information grounded in Arab torical roots in Ancient Arabic medicine, which itself classical medical scholarship of the Middle Ages was was influenced by the ancient medicinal practices of gradually transferred to local traditional healers and to Mesopotamia, Greece, Rome, Persia, and India. During the general public. Arabs relied primarily on their tradi- the Umayyad rule (661-750 A.D.), translations of ancient tional medicine [2]. -
Structural Studies and Spectroscopic Properties of Quinolizidine Alkaloids (+) and (-)-Lupinine in Different Media
Journal of Materials and J. Mater. Environ. Sci., 2019, Volume 10, Issue 9, Page 854-871 Environmental Sciences ISSN : 2028-2508 CODEN : JMESCN http://www.jmaterenvironsci.com Copyright © 2019, University of Mohammed Premier Oujda Morocco Structural Studies and Spectroscopic properties of Quinolizidine Alkaloids (+) and (-)-Lupinine in different media José Ruiz Hidalgo, Maximiliano A. Iramain, Silvia Antonia Brandán* Cátedra de Química General, Instituto de Química Inorgánica, Facultad de Bioquímica. Química y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, (4000) San Miguel de Tucumán, Tucumán, Argentina. Received 21 Aug 2019, Abstract Revised 07 Sept 2019, The quinolizidine alkaloids, as numerous species of lupine (Lupinus spp.), are toxic and Accepted 09 Sept 2019 have biological effect on the nervous system. Hence, four (+) and (-)- molecular structures of quinolizidine alkaloid lupinine, named C0, C1a, C1b and C1c have been theoretically Keywords determined in gas phase and in aqueous solution by using hybrid B3LYP/6-31G* (-)-Lupinine, calculations. The studied properties have evidenced that the most stable C1c form present 1 Structural properties, the higher populations in both media while the predicted infrared, Raman, H-NMR and 13 Force fields, C-NMR and ultra-visible spectra suggest that probably other forms in lower proportion could be also present in water, chloroform and benzene solutions, as evidenced by the low Vibrational analysis, 1 13 DFT calculations. RMSD values observed in the H- and C-NMR chemical shifts. The C1c form presents the lower corrected solvation energy in water while the NBO and AIM studies suggest for *[email protected] this form a high stability in both media. -
Site of Lupanine and Sparteine Biosynthesis in Intact Plants and in Vitro Organ Cultures
Site of Lupanine and Sparteine Biosynthesis in Intact Plants and in vitro Organ Cultures Michael Wink Genzentrum der Universität München, Pharmazeutische Biologie, Karlstraße 29, D-8000 München 2, Bundesrepublik Deutschland Z. Naturforsch. 42c, 868—872 (1987); received March 25/May 13, 1987 Lupinus, Alkaloid Biosynthesis, Turnover, Lupanine, Sparteine [14C]Cadaverine was applied to leaves of Lupinus polyphyllus, L. albus, L. angustifolius, L. perennis, L. mutabilis, L. pubescens, and L. hartwegii and it was preferentially incorporated into lupanine. In Lupinus arboreus sparteine was the main labelled alkaloid, in L. hispanicus it was lupinine. A pulse chase experiment with L. angustifolius and L. arboreus showed that the incorporation of cadaverine into lupanine and sparteine was transient with a maximum between 8 and 20 h. Only leaflets and chlorophyllous petioles showed active alkaloid biosynthesis, where as no incorporation of cadaverine into lupanine was observed in roots. Using in vitro organ cultures of Lupinus polyphyllus, L. succulentus, L. subcarnosus, Cytisus scoparius and Laburnum anagyroides the inactivity of roots was confirmed. Therefore, the green aerial parts are the major site of alkaloid biosynthesis in lupins and in other legumes. Introduction Materials and Methods Considering the site of secondary metabolite for Plants mation in plants, two possibilities are given: 1. All Plants of Lupinus polyphyllus, L. arboreus, the cells of plant are producers. 2. Secondary meta L. subcarnosus, L. hartwegii, L. pubescens, L. peren bolite formation is restricted to a specific organ and/ nis, L. albus, L. mutabilis, L. angustifolius, and or to specialized cells. L. succulentus were grown in a green-house at 23 °C Alkaloids are often found in the second class (for and under natural illumination or outside in an review [1, 2]), but whether a given alkaloid is synthe experimental garden. -
Maculatum L.).-Ii Evidence for a Rapid Turnover of the Major Alkaloids
Phytochcmistry.1961. Vol. 1. pp. 38to 46. Pqamon PressLtd. Printedin lh&id THE ALKALOIDS OF HEMLOCK (CONIUM MACULATUM L.).-II EVIDENCE FOR A RAPID TURNOVER OF THE MAJOR ALKALOIDS J. W. FAIRBAIRN and P. N. SUWAL School of Pharmacy, Brunswick Square, London, W.C.1 (Received 14 February 1961) Abstract-Previous work, based on analyses of samples of &loping fruits collected at weekly intervatS, has been confirmed. Samples wem also collected at 4-hourly and 2-hourly intervals and analyses showed that remarkably rapid changes in the alkaloidal picture took place at short intervals during 24 hr. Further- more, as the coniine (I) content increased, the y-coniceine (II) content decreased and vice versa. This interrelationship was particularly marked during the critical stages of pericarp development, but was not obvious during the development of the vegetative parts, where y-coniceine and conhydrine (III) were the only known alkaloids detected. Since coniine and yconiceine differ only by two hydrogen atoms, it is suggested that these two alkaloids are involved in oxidation-reduction processes in the developing pericarp. The occurrence of the minor alkaloids conhydriie and N-methyl coniine (1V) and the presence of some unknown alkaloids are also reported and commented on. INTRODUCTION IN A previous communication’ it was shown that the total alkaloidal content and the CH(OH)CH$H, proportions of individual alkaloids in hemlock fruit varied with the development of the fruit and with the season. It was suggested that y-coniceine (11) was the precursor of the saturated alkaloids, such as coniine (I), and that this change, which appeared to be rever- sible, is associated with active grbwth. -
Identification and Determination of Unusual Functional Groups
IDENTIFICATION AND DETERMINATION OF UNUSUAL FUNCTIONAL GROUPS E. SAWICKI U.S. Department of Health, Education and Weifare, Cincinnati, Ohio 45226, U.S.A. INTRODUCTION Many of the unusual and unfamiliar analytical methods of yesterday have become the common methods of today. Therefore, when we speak of "unusual" functional groups we refer to those that are now novel but that may evolve with time and use into the usual and well-known. With advances in knowledge of the physical and chemical properties of organic molecules, new types of functional groups are being found, some of which appear strange and unusual at the moment while others are more sharply delineated sub-divisions of well-known functional groups. The sub-divisional functional group contains the original functional group with additional atoms; for example, one sub-division of a ketonic C =Ü func tional group is the -CHz-CO-CH3 grouping. Methods of analysis for compounds containing such a sub-divisional grouping are usually more highly selective. Examples will be given of some well-known families of compounds, each theoretically containing a common functional group which, until recently, had not been exploited for analytical purposes. Environmental health problems have proliferated tremendously in the past 40 years mainly because of the growing complex.ity of the chemical environment in which we live. Examples of this phenomenon are smog and the growing dinginess of the urban atmosphere; this dinginess indicates the accelerating infiltration of our air by man-made pollutants. Because of the increasing chemical pollution of our environment and its sometimes adverse effect on man, other life forms, and man-made objects, it is necessary first to determine the composition of the complicated mixtures with which we are in contact and then to decrease the concentrations ofthe harmful compounds. -
Piperidine Alkaloids: Human and Food Animal Teratogens ⇑ Benedict T
Food and Chemical Toxicology 50 (2012) 2049–2055 Contents lists available at SciVerse ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox Review Piperidine alkaloids: Human and food animal teratogens ⇑ Benedict T. Green a, , Stephen T. Lee a, Kip E. Panter a, David R. Brown b a Poisonous Plant Research Laboratory, Agricultural Research Service, United States Department of Agriculture, USA b Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108-6010, USA article info abstract Article history: Piperidine alkaloids are acutely toxic to adult livestock species and produce musculoskeletal deformities Received 7 February 2012 in neonatal animals. These teratogenic effects include multiple congenital contracture (MCC) deformities Accepted 10 March 2012 and cleft palate in cattle, pigs, sheep, and goats. Poisonous plants containing teratogenic piperidine alka- Available online 20 March 2012 loids include poison hemlock (Conium maculatum), lupine (Lupinus spp.), and tobacco (Nicotiana tabacum) [including wild tree tobacco (Nicotiana glauca)]. There is abundant epidemiological evidence in humans Keywords: that link maternal tobacco use with a high incidence of oral clefting in newborns; this association may be Anabaseine partly attributable to the presence of piperidine alkaloids in tobacco products. In this review, we summa- Anabasine rize the evidence for piperidine alkaloids that act as teratogens in livestock, piperidine alkaloid -
Open Sacher - Phd Dissertation.Pdf
The Pennsylvania State University The Graduate School Eberly College of Science PROGRESS TOWARD A TOTAL SYNTHESIS OF THE LYCOPODIUM ALKALOID LYCOPLADINE H A Dissertation in Chemistry by Joshua R. Sacher © 2012 Joshua R. Sacher Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy May 2012 ii The dissertation of Joshua Sacher was reviewed and approved* by the following: Steven M. Weinreb Russell and Mildred Marker Professor of Natural Products Chemistry Dissertation Advisor Chair of Committee Raymond L. Funk Professor of Chemistry Gong Chen Assistant Professor of Chemistry Ryan J. Elias Frederik Sr. and Faith E. Rasmussen Career Development Professor of Food Science Barbara Garrison Shapiro Professor of Chemistry Head of the Department of Chemistry *Signatures are on file in the Graduate School iii ABSTRACT In work directed toward a total synthesis of the Lycopodium alkaloid lycopladine H (21), several strategies have been explored based on key tandem oxidative dearomatization/Diels-Alder reactions of o-quinone ketals. Both intra- and intermolecular approaches were examined, with the greatest success coming from dearomatization of bromophenol 84b followed by cycloaddition of the resulting dienone with nitroethylene to provide the bicyclo[2.2.2]octane core 203 of the natural product. The C-5 center was established via a stereoselective Henry reaction with formaldehyde to form 228, and the C-12 center was set through addition of vinyl cerium to the C-12 ketone to give 272. A novel intramolecular hydroaminomethylation of vinyl amine 272 was used to construct the 8-membered azocane ring in intermediate 322, resulting in establishment of 3 of the 4 rings present in the natural product 21 in 9 steps from known readily available compounds. -
Quinolizidine Alkaloid Profiles of Lupinus Varius Orientalis , L
Quinolizidine Alkaloid Profiles of Lupinus varius orientalis , L. albus albus, L. hartwegii, and L. densiflorus Assem El-Shazlya, Abdel-Monem M. Ateya 3 and Michael W inkb * a Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt b Institut für Pharmazeutische Biologie der Universität, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. Email: [email protected] * Author for correspondence and reprint requests Z. Naturforsch. 56c, 21-30 (2001); received September 20/0ctober 25, 2000 Quinolizidine Alkaloids, Biological Activity Alkaloid profiles of two Lupinus species growing naturally in Egypt (L. albus albus [syn onym L. termis], L. varius orientalis ) in addition to two New World species (L. hartwegii, L. densiflorus) which were cultivated in Egypt were studied by capillary GLC and GLC-mass spectrometry with respect to quinolizidine alkaloids. Altogether 44 quinolizidine, bipiperidyl and proto-indole alkaloids were identified; 29 in L. albus, 13 in L. varius orientalis, 15 in L. hartwegii, 6 in L. densiflorus. Some of these alkaloids were identified for the first time in these plants. The alkaloidal patterns of various plant organs (leaves, flowers, stems, roots, pods and seeds) are documented. Screening for antimicrobial activity of these plant extracts demonstrated substantial activity against Candida albicans, Aspergillus flavus and Bacillus subtilis. Introduction muscarinic acetylcholine receptors (Schmeller et al., 1994) as well as Na+ and K+ channels (Körper Lupins represent a monophyletic subtribe of the et al., 1998). In addition, protein biosynthesis and Genisteae (Leguminosae) (Käss and Wink, 1996, membrane permeability are modulated at higher 1997a, b). Whereas more than 300 species have doses (Wink and Twardowski, 1992). -
Scientific Opinion
SCIENTIFIC OPINION ADOPTED: DD Month 20YY doi:10.2903/j.efsa.20YY.NNNN 1 Scientific opinion on the risks for animal and human health 2 related to the presence of quinolizidine alkaloids in feed 3 and food, in particular in lupins and lupin-derived products 4 EFSA Panel on Contaminants in the Food Chain (CONTAM) 5 Dieter Schrenk, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl-Kraupp, Christer 6 Hogstrand, Laurentius (Ron) Hoogenboom, Jean-Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, 7 Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather 8 Wallace, Jan Alexander, Bruce Cottrill, Birgit Dusemund, Patrick Mulder, Davide Arcella, Katleen Baert, 9 Claudia Cascio, Hans Steinkellner and Margherita Bignami 10 Abstract 11 The European Commission asked EFSA for a scientific opinion on the risks for animal and human 12 health related to the presence of quinolizidine alkaloids (QAs) in feed and food. This risk assessment 13 is limited to QAs occurring in Lupinus species/varieties relevant for animal and human consumption in 14 Europe (i.e. L. albus, L. angustifolius, L. luteus and L. mutabilis). Information on the toxicity of QAs in 15 animals and humans is limited. Following acute exposure to sparteine (reference compound), 16 anticholinergic effects and changes in cardiac electric conductivity are considered to be critical for 17 human hazard characterisation. The CONTAM Panel used a margin of exposure (MOE) approach 18 identifying a lowest single oral effective dose of 0.16 mg sparteine/kg body weight as reference point 19 to characterise the risk following acute exposure. No reference point could be identified to 20 characterise the risk of chronic exposure.