1 UNIVERSITY COLLEGE LONDON The Asymmetric Synthesis of Decalin Synthons for Use in Flavour and Fragrance Compounds Michael Paul Morris Supervisor: Dr H. C. Hailes PhD 1998 ProQuest Number: U644026 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U644026 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 CONTENTS CONTENTS...........................................................................................................................................2 LIST OF ABBREVIATIONS.............................................................................................................10 ABSTRACT.........................................................................................................................................12 ACKNOWLEDGEMENTS................................................................................................................14 CHAPTER ONE: INTRODUCTION TO GEOSMINAND DEHYDROGEOSMIN 1.0 INTRODUCTION TO GEOSMIN............................................................................................. 18 1.1 SYNTHESES OF GEOSMIN...................................................................................................... 18 1.2 BUSH BOAKE ALLEN AND GEOSMIN................................................................................. 24 1.3 INTRODUCTION TO DEHYDROGEOSMIN......................................................................... 25 1.4 SYNTHESES OF DEHYDROGEOSMIN................................................................................. 25 1.5 THIS PROJECT........................................................................................................................... 27 CHAPTER TWO: BUTAN-2,3-DIOL 2.0 OBJECTIVE................................................................................................................................. 29 2.1 APPROACHES............................................................................................................................ 30 Chemical synthesis ........................................................................................................................... 30 Enzymatic enantioselective resolution .............................................................................................30 Physical enantioselective resolution .................................................................................................31 Enzymatic enantioselective oxidation^reduction .............................................................................. 31 Bacterial fermentation ......................................................................................................................32 Selected approach ............................................................................................................................. 32 2.2 BACTERIAL FERMENTATION APPROACH....................................................................... 33 The carbon source ............................................................................................................................ 33 The temperature............................................................................................................................... 33 The rate of aeration ..........................................................................................................................34 2.2.1 ORIGIN OF STEREOSELECTIVITY IN FERMENTATIONS....................................... 34 Existence of an acetoin racemase .....................................................................................................35 Absence of an acetoin racemase .......................................................................................................36 THE FERMENTATION STUDY.....................................................................................................38 2.3 RESULTS AND DISCUSSION...................................................................................................38 Page 2 2.3.1 GLUCOSE FERMENTATIONS............................................................................................. 39 Reaction time ....................................................................................................................................39 Initial inoculum concentration ......................................................................................................... 39 Initial glucose concentration.............................................................................................................39 Agitation ............................................................................................................................................39 Aeration .............................................................................................................................................39 Analysis .............................................................................................................................................39 Results...............................................................................................................................................41 2.3.2 INFERENCES............................................................................................................................44 Effect of time (graph 2 and graph 3) ................................................................................................ 44 Effect of agitation (graph 4 and graph 5 ) ......................................................................................... 44 Effect of inoculum Concentration .................................................................................................... 44 Effect of initial glucose concentration ............................................................................................. 45 Effect of aeration .............................................................................................................................. 45 Isomer specificity ..............................................................................................................................45 2.3.3 FURTHER INVESTIGATIONS.............................................................................................. 45 Extraction procedure ........................................................................................................................ 45 Carbon source .................................................................................................................................. 47 Variation of strain ............................................................................................................................ 47 2.3.4 CONCLUSIONS OF THE FERMENTATION STUDY........................................................ 48 2.4 ENZYMATIC RESOLUTIONS................................................................................................. 49 2.4.1 MODE OF A C TIO N ..................................................................................................................49 Water-miscible organic co-solvent system ....................................................................................... 50 Anhydrous organic solvents ............................................................................................................. 50 Diphasic systems of water and a water immiscible organic solvent ................................................. 51 2.4.2 SPECIFICITY IN ORGANIC SOLVENTS............................................................................ 51 2.4.3 ENZYME SELECTION........................................................................................................... 51 THE ENZYMATIC RESOLUTION STUDY.................................................................................. 52 2.5 RESULTS AND DISCUSSION ................................................................................................... 52 Enzyme and acyl donor selection ..................................................................................................... 52 Experimental protocol ...................................................................................................................... 53 Analysis ............................................................................................................................................ 53 2.5.1 RESULTS: CANDIDA CYLINDRACEA AND PORCINE PANCREATIC LIPASES.......... 54 Candida cylindracea lipase (C C L) ...................................................................................................54 Porcine pancreatic lipase (PPL) ....................................................................................................... 54 2.5.2 INFERENCES ........................................................................................................................... 55 2.5.3 RESULTS: CANDIDA ANTARCTICA LIPASE..................................................................... 56 Product distribution over time.........................................................................................................