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Towards the Total Synthesis of 7-Epi-Clusianone

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Towards the Total Synthesis of 7-Epi-Clusianone University of Kentucky UKnowledge Theses and Dissertations--Chemistry Chemistry 2017 TOWARDS THE TOTAL SYNTHESIS OF 7-EPI-CLUSIANONE Shubhankar Dutta University of Kentucky, [email protected] Digital Object Identifier: https://doi.org/10.13023/ETD.2017.266 Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Dutta, Shubhankar, "TOWARDS THE TOTAL SYNTHESIS OF 7-EPI-CLUSIANONE" (2017). Theses and Dissertations--Chemistry. 79. https://uknowledge.uky.edu/chemistry_etds/79 This Doctoral Dissertation is brought to you for free and open access by the Chemistry at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Chemistry by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained needed written permission statement(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine) which will be submitted to UKnowledge as Additional File. I hereby grant to The University of Kentucky and its agents the irrevocable, non-exclusive, and royalty-free license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless an embargo applies. I retain all other ownership rights to the copyright of my work. I also retain the right to use in future works (such as articles or books) all or part of my work. I understand that I am free to register the copyright to my work. REVIEW, APPROVAL AND ACCEPTANCE The document mentioned above has been reviewed and accepted by the student’s advisor, on behalf of the advisory committee, and by the Director of Graduate Studies (DGS), on behalf of the program; we verify that this is the final, approved version of the student’s thesis including all changes required by the advisory committee. The undersigned agree to abide by the statements above. Shubhankar Dutta, Student Dr. Robert B. Grossman, Major Professor Dr. Mark A. Lovell, Director of Graduate Studies TOWARDS THE TOTAL SYNTHESIS OF 7-EPI-CLUSIANONE DISSERTATION A dissertation submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in the College of Arts and Sciences at the University of Kentucky By Shubhankar Dutta Lexington, Kentucky Director: Dr. Robert B. Grossman, Professor of Chemistry Lexington, Kentucky 2017 Copyright © Shubhankar Dutta 2017 ABSTRACT OF DISSERTATION TOWARDS THE TOTAL SYNTHESIS OF 7-EPI-CLUSIANONE Polycyclic polyprenylated acylphloroglucinols (PPAPs) are plant- (Guttiferae) derived natural products. They have fascinating bicyclo[3.3.1]nonane-2,4,9-trione or [3.2.1]nonane-2,4,8-trione cores decorated with prenyl or geranyl groups. More than 200 PPAPs have been isolated, but only a few of them have been synthesized, although most of the synthesized PPAPs are of type A and have an exo substituent at C (7). Here, we are trying to make a type B 7-endo PPAP, 7-epi-clusianone. The synthetic plan involves an alkynylation–aldol strategy to construct the bicyclic core. Having established the bicyclic core, the synthesis presents a new challenge: the oxidation of a very hindered 2-alkenone to the β-hydroxy 2-alkenone. KEYWORDS: Polycyclic polyprenylated acylphloroglucinols, 7-epi-clusianone, bicyclo[3.3.1]nonane, 2-alkenone, β-hydroxy 2-alkenone Shubhankar Dutta 07/10/2017 TOWARDS THE TOTAL SYNTHESIS OF 7-EPI-CLUSIANONE By Shubhankar Dutta Dr. Robert B. Grossman Director of Dissertation Dr. Mark A. Lovell Director of Graduate studies 07/10/2017 Date Dedicated to My Mother, Sumita Dutta Acknowledgements Born in a family of lawyers, where every household member is destined to become a gen-next lawyer to carry forward the legacy of the family business, a ‘renegade’ appeared—who never thought of studying in the United States, let alone dreaming about a Ph.D. in Chemistry. I owe this incredible feat to some extraordinary people, or perhaps better to say some pristine minds, who have left an impression on me. First and foremost, I shall start with Dr. Robert B. Grossman, my research advisor, whom I admire and thank for providing me with the opportunity to research in his group. He gave me hope and restored my confidence that I could be a research scientist when my career hit rock-bottom. His stoic endurance has always spellbound me and he never discouraged me from discussing ideas, no matter how puerile they may be. In many ways, he is, I believe, reminiscent of great Napoléon, who once said, there are no bad soldiers, only bad generals. I express my sincere gratitude to my committee member, Dr. Cammers, who always inspired me to push the boundaries of knowledge. Dr. Selegue and Dr. Röhr from the UK College of Pharmacy have always enriched my knowledge by offering insightful thoughts during committee meetings and discussions. I cordially thank them for accepting my request to be on my research committee. John Layton and Art Sebesta are the other two pillars of my research. John always helped me understand NMR, while Art has provided me with assistance fixing the instruments in the lab, even on Saturdays. Dr. Patwardhan was instrumental in guiding me through difficult times. Thank you, Dr. Patwardhan. My friends at UK also deserve credit. Subbu, Aman, Nikhil, and Rahul have always ‘tolerated’ me and helped me to grow as a scientist. I am grateful to them. I am also grateful to my lab mates, especially Meenakshi for her support and encouragements. iii Life is full of subtle moments, and each moment tells a story that might not have a logical conclusion at the time when it was told, but it altered my course. I solemnly bow my head to those people who were the center of those moments. Dr. Subhabrata Sen was one of such persons who laid the ‘seed’ for me to pursue a Ph.D. Without him, I could not have reached the US to continue my journey as a student. Dr. Debasis Chakraborty was instrumental in nurturing the plant that sprouted from that early seed. I am grateful to the late Biresh Chandra Bose, whom I revered because of his memory and command of English literature. He would be happy today to know that I have written 250 pages of a dissertation in English, which is not my native language. And I am thankful to all those teachers who have enlightened my young mind in times of confusion. Here, I cannot forget Debiprasad Chakraborty who compelled me to switch to Chemistry from English for some unknown reason. Now, I feel that it was ‘destined’ to happen—a term scientists always have avoided. My math teacher, Paresh Govinda Sinha, needs a special mention since he sent an application form for Chemistry for me, and I did not know that fact. And Chand aunt, who is no more, used to be a tutor till my seventh grade and subconsciously taught me that there is no alternative to hard work. Charity begins at home, the adage says. Everyone has first teachers in the form of parents. My mother, Sumita Dutta, is my first teacher who has been the bedrock of my character, ever since I got a conscience. She did not complete her bachelor's, but she always surprises me with her intellect and poses to me a question—what does education mean? My father, Soumyen Dutta, has been a great teacher without losing his temper—keeping his calm in dire situations indicating how astute a lawyer he is, and teaching me how to live a peaceful life. He always tells me how to fight back after a defeat. Without my parents' iv support, I could not be here. My only little sister, Soumi, has supported me through these years by taking care of my parents. I am very much thankful to her. Last but not least, Sayantani Guha, my wife, my lady love, I say, thank you for your unconditional support. She has suffered the most because of me, a capricious husband, and it was not easy to take care of a graduate student like me, although she has never complained about it. Thank you. v Table of Contents Acknowledgements ............................................................................................................ iii List of Figures ..................................................................................................................... x List of Tables .................................................................................................................... xii List of Schemes ................................................................................................................ xiii 1 Introduction to natural products ................................................................................ 18 1.1 Introduction ................................................................................................................... 18 1.2 Introduction to PPAPs ................................................................................................... 20 1.3 Classification of PPAPs ................................................................................................ 22 1.4 History of PPAPs .......................................................................................................... 24 1.5 Revisiting some structures of type B endo PPAPs .......................................................
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