UNIVERSITY OF NAIROBI COLLEGE OF PHYSICAL AND BIOLOGICAL SCIENCES DEPARTMENT OF CHEMISTRY PHYTOCHEMICAL INVESTIGATION OF THREE ERYTHR1NA SPECIES AND TECLEA NOBILIS BY CHEPKIRUI CAROLYNE A THESIS SUBMITED IN PARTIAL FULFILMENT FOR THE AWARD OF THE DEGREE OF MASTER OF SCIENCE, UNIVERSITY OF NAIROBI 2012 DECLARATION This thesis is my original work and has never been presented for a degree in any university. ..... ( f e - ............ CHEPKJRUI CAROLYNE 156/60646/2011 SUPERVISORS / PROF ABIY YENESEW Department of Chemistry University o f Nairobi Dr MARTIN MBUGUA Department o f Chemistry University o f Nairobi DEDICATION This thesis is dedicated to my beloved parents; Mr. Peter Kenduiwo, Mrs. Mary Kenduiwo and my beloved son Gideon Kipngetich. Thank you for your great love, support and for giving me direction in life. iii ACKNOWLEDGEMENT My deepest gratitude goes to my supervisors Prof. Abiy Yenesew, Dr. Martin Mbugua for their continuous guidance, encouragement and support throughout the research and write-up of the thesis. 1 would like to sincerely thank Dr. Albert Ndakala for his guidance and feedback on developments from the Department of Chemistry and the School of Postgraduate studies. Thank you very much. 1 am sincerely grateful to Dr. Matthias Heydenreich, University of Potsdam, for analyzing samples on high resolution NMR. 1 am grateful to the academic and technical staff of the Department of Chemistry, University of Nairobi for their assistance and support. I am also thankful to the former and current members of the Natural Product Research Group, Department of chemistry University of Nairobi, for their support and assistance during the course of my study. / I sincerely thank PhD students Martha Induli and Negara Abdisa, Msc student Daisy Nyawira and undergraduate student Dickens Ouma for their support, encouragement and their advice throughout the entire period. I sincerely thank my parents for giving me an opportunity to achieve my goals by paying my tuition fees; 1 also thank my siblings, colleagues and George for their endless love and support. IV LIST OF ABBREV IATIONS AND SYMBOLS HMQC Heteronuclear Multiple Quantum Coherence (1 Jen) HMBC Hetronuclear Multiple Bond Correlation CJ c h , 3J c i i ) COSY Correlated Spectroscopy NOESY Nuclear Overhauser and Exchange Spectroscopy NMR Nuclear Magnetic Resonance ID One Dimensional analysis 2D Two Dimensional analysis UV Ultra Violet MHz Mega Hertz Hz Hertz J Coupling constant S Singlet cl Doublet del Doublet of a doublet t Triplet TLC Thin Layer Chromatography PTLC Preparative Thin Layer Chromatography IC50 Concentration of 50% Inhibition RB Root bark SB Stem bark F Flower v TABLE OF CONTENTS DEDICATION.................................................................................................................................... iii ACKNOWLEDGEMENT....................................................................................................................iv LIST OF ABBREVIATIONS AND SYMBOLS.................................................................................... v ABSTRACT.......................................................................................................................................xiii CHAPTER ONE.................................................................................................................................. 1 1.0 INTRODUCTION.................................................................................................................... 1 1.1 General......................................................................................................................................1 1.2 Problem statement...................................................................................................................... 2 1.3 Justification.............................................................................................................................. 2 1.4 Objectives................................................................................................................................. 3 1.4.1 General objectives..................................................................................................................3 1.4.2 Specific objectives................................................................................................................. 4 CHAPTER TWO.................................................................................................................................5 2.0 LITERATURE REVIEW...........................................................................................................5 2.1 Alkaloids..................................................................................................................................6 2.2 BOTANICAL INFORMATION................................................................................................8 2.2.1 THE FAMILY FABACEAE..................................................................................................8 2.2.2 The genus Erythrina.................................................................................................................... 9 2.2.2.1 Erythrina abyssinica.............................................................................................................. 9 2.2.2.2 Erythrina burttii................................................................................................................... 9 2.2.2.3 Erythrina brucei.......................................................................................................................10 2.2.3 Ethnomedical information on the genusErythrina ..................................................................11 2.2.4 Biological activities of Erythrina species............................................................................... 13 2.3 Phytochemical information....................................................................................................... 15 VI 2.3.1 Compounds reported from the genus Erythrina.....................................................................15 2.3.1.1 Flavonoids........................................................................................................................... 15 2.3.1.1.1 Flavanones of Erythrina .................................................................................................. 17 2.3.1.1.2 Isoflavonoids of Erythrina................................................................................................ 22 2.3.1.1.3 Isoflavanones of Erythrina............................................................................................... 23 23.1.1.4 isoflavans of Erythrina..................................................................................................... 26 2.3.1.1.5 Isoflavones of Erythrina................................................................................................... 27 2.3.1.1.6 Isoflav-3-enes of Erythrina............................................................................................... 29 2.3.1.1.7 Pterocarpanoids of Erythrina.............................................................................................30 2.3.1.1.8 Other minor flavonoids of tythrina....................................................................................33 2.4 Alkaloids................................................................................................................................35 2.4.1 Structural classification of Erythrina alkaloids........................................................................... 35 2.4.1.1 Aromatic erythrinan alkaloids..................................................................................................35 2.4.1.2 Non-aromatic erythrinan alkaloids...........................................................................................36 2.5 The family rutaceae.................................................................................................................40 2.5.1 The genus teclea.................. 40 2.5.3 Botanical information on Teclea nobilis............................................................................... 40 2.5.4 Ethnomedical information on the genus Teclea.................................................................... 41 2.5.5 Biological activities of the genus Teclea............................................................................... 42 2.6 Compounds reported the genus Teclea..................................................................................... 42 2.6.1 Furoquinoline alkaloids........................................................................................................43 2.6.2 Acridone alkaloids of the genus Teclea................................................................................. 48 CHAPTER THREE.............................. ,........................................................................................... 51 3.0 EXPERIMENTAL.................................................................................................................51 3.1. Instrumentation....................................................................................................................... 51 vii 3.2 Chromatographic methods.................... 51 3.3 Plant material.......................................................................................................................... 52 3.3.1 Teclea nobilis.....................................................................................................................