Synthesis of geminal bisphosphonates as potential inhibitors of GGDPS

Abstract

Dr. Natalie Ulrich, who taught me lab techniques, edited my seminar slides and comps documents, as well as shared a love for Michael Buble's music. Thank you to Dr. John Kodet and Dr. Alyssa Hartung for being patient and answering my numerous questions and to Dr. Xiang Zhou for guiding me when I first began working on this project. A special thanks goes to Joseph Metzger for his efforts in the synthesis of some final targets, as well as his contributions of intermediates and willingness to assist with anything I asked. I am glad to have had the opportunity to mentor Joe this past year, and I truly appreciate his hard work, input, and positive attitude. In addition to Joe, I would like to thank Dr. Xiang Zhou, Rebekah Shippy, Michael Welford, and Benjamin Foust for providing useful intermediates. Also, I will cherish the friendships with Kevyn Gardner, Rebekah Shippy and Dr. Alyssa Hartung. I will not forget our many walks downtown to get coffee (even in the freezing, snowy, and icy Iowa winters).Also, I would like to express my appreciation for our collaborator Dr. Sarah A. Holstein, as well as Ella Born and Cheryl Allen both who have worked in Dr. Holstein's lab, for providing the biological data for the triazole bisphosphonates described in this thesis. Thank you also to Dr. Jacqueline Reilly, a member of Dr. Raymond J. Hohl's research group for helpful discussions and supplying the cellular and enzyme assay data for the digeranyl bisphosphonate analogues. To Dinith Jayanetti and In Hyun Hwang of the Gloer research group, I would like to thank them for their help in acquiring 2D NMR and HPLC data, respectively.The hard work of the University of Iowa Chemistry Department staff also should not go unnoticed. There are many dedicated individuals who have vi made my time at the University of Iowa a wonderful experience. Thank you to Janet Kugley for making me feel at ease when I first arrived in the department and to Sharon Robertson for making sure that I was up-to-date with everything.I also greatly appreciate Dr. Lynn Teesch and Vic Parcell in the mass spectrometry facility for obtaining high resolution mass spec data for numerous compounds reported in this thesis. Not to mention, the NMR data reported here would not have been possible without the maintenance of the NMR facility by Dr. Santhana Velupillai and his staff. Financial support provided by NIH, Dean's Graduate and Iowa AGEP fellowships from the University of Iowa Graduate College, and an NIH Predoctoral Fellowship in Biotechnology from the Center of Biocatalysis and Bioprocessing, are gratefully acknowledged. Last but not least, I would like to extend my sincere appreciation for my family and friends. I want to thank my friends near and far, especially those in Campus Christian Fellowship, for their encouragement and prayers throughout my time in graduate school. A special thank you goes to my roommate Kaycee Lynn Pancake. I have truly appreciated her friendship, especially during the times she was my sounding board, as well as when she allowed me the o...