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Other___________________________________________________________________________ UMI Part 1 Isolation and Structure Elucidation of Ditcrpcncs from Amphiachyris amoena (Shinners) Solbrig Part 2 Synthesis of Mcthoxy-Mcthy lenedioxy Isoquinolones DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Donal P. O'Mathuna, B.Sc.(Pharm.) The Ohio State University 1988 Dissertation Committee: Approved by Raymond W. Doskotch, Ph.D. Duane D. Miller, Ph.D. Larry W. Robertson, Ph.D. Robert W. Brucggemcier, Ph.D. Raymond W. Doskotch, Adviser College of Pharmacy DEDICATION To my Mother and Father, and Cheri - ii - ACKNOWLEDGEMENTS I express sincere gratitude to the following organizations and individuals for their assistance during the course of my graduate studies: The Ohio State University, the College of Pharmacy and the Division of Medicinal Chemistry and Pharmacognosy, for their generous financial support. The faculty of the Division of Medicinal Chemistry and Pharmacognosy, for their complete availability, and eagerness to share their experience and knowledge. The staff of the Division of Medicinal Chemistry and Pharmacognosy who have helped me so much over the years, especially Jack Fowble, Ernie Corrigan, Carol Settles, and Rose Smith. Paul Campbell, the resident computer expert at the College of Pharmacy, for his invaluable advice and many hours of help, without which the printing of this document would not have been possible. My colleagues in the lab, Shoei-Shcng l/cc, Jocelyn Burke, Fathalla Harraz, Tim Driscoll, Chayan Picheansoonthan, Mike Pcolinski, Jeff Engle, and Mike Darson, for their friendship, support, and help. Mr. R. Wcisenburger, and Dr. D. Chang, at the Ohio State University Chemical Instrument Center, for the high resolution-mass spectra. Dr. R. Doskotch, for his advise, and guidance, and helping me to mature as a scientist and a person. My parents, without whom I would not have had the opportunity to obtain this education, nor the character to attempt it. Mairc, Eamonn, and F-oin, for their support and friendship. Cheri, my wonderful wife, for keeping me going when things were rough, building me up when I was down, making so many sacrifices, and being such a delight to come home to. Finally, my Lord, Jesus Christ, through Whose power what I have investigated was created, for giving me all that I have, including the ability and the opportunity to do this research. VITA April 16, 1961 Bom - Ballyshannon, Ireland 1982 B.Sc. Pharmacy, Trinity College, Dublin, Ireland 1983 - 1988 Graduate Teaching Associate, College of Pharmacy, The Ohio State University FIELDS OF STUDY Major Field: Natural Products Chemistry TABLE OF CONTENTS PAGE D ED ICA TIO N ............................................................................................................................... ii ACKNOWLEDGEMENTS.................................................................. iii VITA ...................................................................................... iv LIST OF T A B L E S ............................................................................................................................ ix LIST OF FIGURES ......................................................................................................................... xi LIST OF ABBREVIATIONS....................................................................................................... xvii RESULTS AND DISCUSSION Part I: Isolation and Structure Elucidation of Ditcrpcncs from Amphiachyris amocna (Sliinners) Solbrig .......................................................................................................... I INTRODUCTION ................................................................................................................ 2 ELUCIDATION OF DITERPENE STRUCTURES....................................................... 7 Extraction of Plant Material .......................................................................................... 7 Amoenolidc A 6,19-diacetate ( 1 ) ........................................................................................10 Amocnolide A ( 4 ) ................................................................................................................20 Amoenolide A 19-Acetate ( 8 ) ............................................................................................. 28 Amoenolidc A 6 -Acetatc (9) ............................................................................................. 29 Amoenolidc A 19-Glucoside (1 0 ) ....................................................................................... 30 Amoenolide A 19-AJdchyde ( 1 2 ) ....................................................................................... 33 Amoenolide B (14) 36 Amoenolide C (15) 39 Amoenolide D (16) ............................................................................................................ 41 Amoenolide E (17) 46 Amocnolide F (19) 50 - v - Amoenolide G (21) ......................................................................................................... 53 Amoenolide II (23) 61 Amocnolide J ( 2 5 ) ............................................................................................................... 65 Amoenolide K (29) ......................................................................................................... 70 Amoenolidc K 19-Acetate ( 3 0 ) ......................................................................................... 75 Amoenolide L (32) 77 PIIOTOOXYGENATION OF AMOENOLIDE A 2,6,19-TRIACETATE ..................... 87 Hydroperoxide 37 ................................................................................................ 90 Epoxide 3 9 .......................................................................................................................... 93 Epoxide 4 0 .......................................................................................................................... 96 Grindelane 41 99 Alcohol 44 ........................................................................................................................ 102 EXPERIMENTAL ............................................................................................................... 105 Plant Material .................................................................................................................. 105 Equipment and Reagents ................................................................................................ 105 R cagpnts ..................................................................................................................... 105 Thin Layer Chromatography .................................................................................... 106 Column Chromatography Adsorbents ....................................................................