Oxidation of Complex Molecules: From Nature to the Flask A thesis presented by Quentin Michaudel to The Scripps Research Institute Graduate Program in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Chemistry for The Scripps Research Institute La Jolla, California May 2015 © Copyright 2015 by Quentin Michaudel All rights reserved. ii Thesis acceptance form goes here iii Dedicated to my parents for always supporting my dreams, to Clément and Louise with the hope that they follow their own, and to the rest of my family and friends for always being around. In memory of the victims of the Charlie Hebdo shooting on 7 January 2015. iv If I have seen further it is by standing on the shoulders of giants. — Isaac Newton. v Acknowledgements Phil: Thank you for giving me a chance, first as a visiting student, then as a graduate student. It was quite a ride, but if I had to start my PhD again, I would not change a thing. I guess, for a PhD more than anything, the journey matters at least as much as the destination. The almost 6 years I spent in the lab taught me how to be an independent researcher, how to write papers and deliver talks and how to collaborate with other scientists, particularly those from other fields or from industry. I have been a privileged witness of your success and I hope that I can carry forward some of your secret recipes to fulfill my dream of becoming a successful professor one day. Prof. Ryan Shenvi: Thank you for all the advice you gave me along the way, whether it was simply on how to set up a reaction or in helping me choose a post-doctoral position. Thank you also for giving me the opportunity to TA one of your classes. Prof. Jin-Quan Yu: Thank you for watching over my developments in graduate school and dispensing some always-insightful opinions on my organometallic chemistry. Prof. Scott Snyder: Thank you for agreeing to fill in for Prof. Nicolaou; I am glad that I can keep a strong Corey influence in my committee. Even if I have known you for a shorter time than the rest of my committee, I always enjoyed talking with you about chemistry or anything else. Prof. Brad Moore: I had an amazing time working with Robin, Aki and you, as well as our other collaborators at Michigan and the Salk Institute. This collaboration taught me so much, not only in terms of the science, but also about the practical aspects of working with people that have different expertise than mine. Thank you for agreeing to serve on my thesis committee; I am glad to have an external committee member with whom I already share a scientific bond. Aki, Robin: I had a great time collaborating with you and the folks at Michigan and Salk. My biology/enzymology definitely improved a lot thanks to you. Scott, Alicia, John, Brad: I got the chance to be part of many interesting collaborations with BMS and to work with all you. I finally met most of you at the symposium there, which was a great event. Working on real-life problems with your respective teams was extremely educational. vi Taylor: With Yoshi and Phil of course, you are the only person that has been in the lab for all my PhD! Thank you for coping with my terrible handwriting on all the order sheets I filled and for always providing some help when I needed some. Tom: Thank you for all the life and chemistry advice that you provided me when I started as a young visiting student and all throughout my PhD. In particular, thank you for taking the time in your busy professor schedule to help me choose a post-doc position. I hope I won’t disappoint you at Cornell! Noah: Along with Tom, you certainly were a model I wanted to emulate when I started grad school. Even if we only briefly overlapped in the lab, this period of time influenced my views on chemistry and grad school a lot. Will: You were a great hoodmate, as much for chemistry knowledge than for fun moments and I hope we can keep in touch in the future, especially since I am following your footsteps in term of academic path! Hans: Even though I did not always understand your jokes or obscure references, working next to you in the office, as well as in the lab was a great experience. You’re probably one of the smartest people I have ever met! Dave Sarlah: Thank you for all the chemistry tips and ideas, as well as all the chemicals you let me borrow from the KC lab. Your work ethic and passion always inspired me. Brady: Thank you for teaching me how to use your glove box and all your chemistry advice. You’re a truly unique character that I won’t forget anytime soon. Nick: It was great to share with you all the similar miseries we encountered while working on C–H oxidations of triterpenes; as well as going out in Hillcrest bars with you. I wish you the best for your post-doc. Rodrigo: I would probably not have been able to work as hard during my PhD if you hadn’t been pushing yourself like crazy every night across the hall. I’m glad you got the job that you deserved. Emily, Dane, KFoo: You were a great group of students to follow and work along in the lab. I hope we will stay in touch in the future and I know you will do great in your respective companies. vii Paul, Dave, Tim, Ian, Cindy, Jonathan: I interacted with all of you in different ways, but I have learned from all of you guys. I am proud to be following you on the Baran lab family tree. Cindy, thanks for having been a great host at BMS! Ryan G: You were a truly nice baymate and officemate and I am wishing you the best for your career. I’m sure you’ll do great in whatever field you choose. Nathan: I got the chance to know you better during our Jersey trip and as a roommate in Lake Arrowhead. Good luck for your post-doc with Prof. Corey, I’m sure it will be memorable! Brandon: You were “un put*** d’enc*** de ta mère”, but I might not have survived my PhD without your coffee machine! I hope you will improve your French and learn words other than the cursing ones. Matt: You are one of the nicest people I met in the US and I hope you will find the path to your dream job soon, because you really deserve it! Thanks for teaching me basketball tactics and football rules. My best to Sarah, Keene and you! J-Lo: Thanks for sharing your music and Apple mania, as well as for being a considerate, and sometimes crazy, baymate. You’ve been very successful so far, I have no doubt it will continue. Ruben: My knowledge of the US and Mexican culture definitely improved through all the interesting (to say the least) talks we had in the office. I will miss those at Cornell! Ming: Your unconditional love for the Mannschaft and the Bayern Munich amused me as much as your chemistry knowledge amazed me. I know that your PhD experience might be rough on you sometimes, but hang in there, the end of the tunnel is near! Art: Ruben and you are definitely forming an entertaining pair in the lab. My idea of Oxford’s finest has slightly changed after interacting with you for almost three years, but you’ll come down as Maoecrystal V’s champion! Yiyang: You’re carrying the oxidase phase torch now and I’m waiting to read all the amazing science that you will come out with. I will think of you everytime Beyoncé is playing on the radio! viii Marcus: I didn’t have the chance to really work with you, but I’m sure that your organometallics training will prove fruitful in the Baran lab. Jacob, Sebastian, Roro, Hang, Leah: I didn’t get to know you guys as well as your predecessors, but I’m sure that the Baran and Shenvi labs are in good hands with your generation. At least, I hope so!! Devon: Visiting Paris with you for two days remains one of the excellent memories of my grad school time. And the story of your one week of employment after your defense is in the top 10 of the funniest stories I have ever heard! Greg: You’re an extremely nice and funny person and I hope we’ll stay in touch in the future. Good luck in the Romesberg lab! Dan, Kanny: After all these years, we crossed the finish line around the same time! Congratulations on your new jobs! Peter, Kelvin: You guys were great classmates and I hope we’ll stay in touch! Shun Su: You were the most influential person in my chemistry learning phase and I would not have accomplished anything I’ve done during my PhD without your always patient and positive teaching during my internship. Your scientific curiosity and your problem solving skills are truly inspiring. Probably 95% of the way I do or think about chemistry comes from you, so I owe you a huge thank you and I hope we will keep in touch, because I still have a lot to learn! Ke Chen: I don’t know how many times you jokingly swore at me, but you were really helpful and influential in my early days in the lab.