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Synthesis and Evaluation of Novel Biologically Active Compounds University of New Orleans ScholarWorks@UNO University of New Orleans Theses and Dissertations Dissertations and Theses Spring 5-22-2020 Synthesis and Evaluation of Novel Biologically Active Compounds Madhurima Das University of New Orleans, [email protected] Follow this and additional works at: https://scholarworks.uno.edu/td Part of the Medicinal-Pharmaceutical Chemistry Commons, and the Organic Chemistry Commons Recommended Citation Das, Madhurima, "Synthesis and Evaluation of Novel Biologically Active Compounds" (2020). University of New Orleans Theses and Dissertations. 2736. https://scholarworks.uno.edu/td/2736 This Dissertation is protected by copyright and/or related rights. It has been brought to you by ScholarWorks@UNO with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Dissertation has been accepted for inclusion in University of New Orleans Theses and Dissertations by an authorized administrator of ScholarWorks@UNO. For more information, please contact [email protected]. Synthesis and Evaluation of Novel Biologically Active Compounds A Dissertation Submitted to the Graduate Faculty of the University of New Orleans in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry by Madhurima Das B.S. University of Delhi, 2012 M.S. University of Leeds, 2014 M.S. University of New Orleans, 2018 May, 2020 To my family for their continued love and support ii ACKNOWLEDGEMENTS I would like to express my deep and sincere gratitude to my advisor Prof. Mark L Trudell for giving me the opportunity to do research in his laboratory. I would also like to thank him for his continuous support and guidance during my doctoral studies and research, for his patience, motivation, enthusiasm, and immense knowledge. His dynamism, vision, sincerity and motivation have deeply inspired me. He has taught me the methodology to carry out independent research and to present the research as clearly as possible. It was a great privilege and honor to work and study under his guidance. I could not have imagined having a better advisor and mentor for my doctoral research. I would like to extend my heartfelt thanks to Dr. Stacey Lomenzo for guiding me through my teaching assistant duties. She was always patient, had excellent organizational skills and strong work ethic. I would like to thank her for being so friendly and approachable. She has been like my family and made it easier for me settle down in a new environment. I would like to thank the rest of my thesis committee: Dr. Branko Jursic, Dr. Steven Rick and Dr. Viktor Poltavets, for their encouragement and insightful comments. I would like to thank Dr. Nicolas G Bazan and Dr. Surjyadipta Bhattacharjee at Louisiana State University Health Sciences Center for completing all the preliminary biological evaluations for my compounds. I would like to thank Dr. Phoebe Zito for guiding me through the hydrophobicity studies and for teaching me UV-vis spectroscopy. iii I would like to express my thanks to my fellow colleagues in the Trudell group: Maria Lindsay and Ryan McKinnie, who helped me settle in when I first joined the group. They were extremely supportive and I am grateful for their generosity and encouragement. A big thanks to my dear friends and labmates Jumanah Hamdi and Nichole Pianovich who have stood by me through all the ups and down in the past 5 years. I could not have asked for better labmates and friends. I will always cherish the memories of working with them and will be forever grateful for their support and encouragement. Last but not the least I am extremely grateful to my parents for their love, prayers, and sacrifices for educating and preparing me for my future. I could not have done this without them. iv TABLE OF CONTENTS List of schemes .................................................................................................................. vi List of figures ..................................................................................................................... xi List of tables ..................................................................................................................... xiv List of abbreviations ........................................................................................................ xvi Abstract .......................................................................................................................... xviii Chapter 1 ..............................................................................................................................1 Chapter 2 ............................................................................................................................62 Chapter 3 ..........................................................................................................................114 References ........................................................................................................................157 Appendix ..........................................................................................................................170 Vita ...................................................................................................................................185 v LIST OF SCHEMES Scheme 1 Synthesis of organic nitrates ...........................................................................5 Scheme 2 Alkaline hydrolysis of nitrate esters ................................................................5 Scheme 3 Synthesis of 12 (Route 1) ..............................................................................13 Scheme 4 Synthesis of 12 (Route 2) ..............................................................................13 Scheme 5 Synthesis of SCP-1 (Route A) ...................................................................... 14 Scheme 6 Synthesis of SCP-1 (Route B) .......................................................................15 Scheme 7 Synthesis of SCP-123 ....................................................................................16 Scheme 8 Retrosynthetic route for synthesis of NO-SCP-1 analogs .............................17 Scheme 9 Synthesis of chloroalkanoyl esters of SCP-1 ................................................22 Scheme 10 Attempted synthesis of 24b ...........................................................................24 Scheme 11 Synthesis of nitrate esters 24a-d using optimized conditions .......................29 Scheme 12 Attempted synthesis of nitrate ester analogs of SCP-123 (strategy 1) ....................................................................................................34 Scheme 13 Attempted synthesis of nitrate ester analogs of SCP-123 (strategy 2) .....................................................................................................35 Scheme 14 Synthesis of -glycoside tetraacetate of 18 using POCl3 as catalyst ............34 Scheme 15 Synthesis of O-glycoside tetraacetate of 18 using BF3•OEt2 as catalyst.......37 Scheme 16 Synthesis of -O-glycoside tetraacetate of SCP-1 ........................................38 vi Scheme 17 Synthesis of -O-glycoside of SCP-1 ...........................................................39 Scheme 18 Synthesis of amides of SCP-1 using amino alcohols 32-37 ..........................40 Scheme 19 Synthesis of amide 44 ...................................................................................41 Scheme 20 Synthesis of amides of SCP-1 using amino acids 45 and 46 ........................42 Scheme 21 Synthesis of diarylmethane using Friedel-Crafts alkylation .........................65 Scheme 22 Synthesis of diarylmethanes using indium (III) chloride as catalyst ............66 Scheme 23 Bronsted and Lewis acid catalyzed arylation ................................................67 Scheme 24 Synthesis of diarylmethanes using metal free C-C bond formation ..............67 Scheme 25 Synthesis of diarylmethanes using triphenylphosphine ditriflate .................68 Scheme 26 Copper catalyzed synthesis of diarylmethanes using Grignard reagent ............................................................................................................68 Scheme 27 Palladium catalyzed synthesis of diarylmethanes using organostannates ..............................................................................................69 Scheme 28 Synthesis of diarylmethanes using Suzuki-Miyaura coupling ......................69 Scheme 29 Synthesis of diarylmethanes using potassium aryltrifluoroborates ...............70 Scheme 30 Synthesis of diarylmethanes using Stille coupling ........................................70 Scheme 31 Synthesis of diarylmethanes using Kumada coupling...................................71 Scheme 32 Synthesis of diarylmethanes using Hiyama coupling ...................................72 Scheme 33 Synthesis of diarylmethanes using Negishi coupling ....................................72 vii Scheme 34 Lewis acid mediated synthesis of diarylmethanes ........................................73 Scheme 35 Synthesis of diarylmethanes via benzylic ester rearrangement .....................73 Scheme 36 Synthesis of N-substituted azetidine .............................................................78
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