2011 Lester A. Mitscher Symposium
May 12–14, 2011
Lawrence, KS
University of Kansas, Pharmacy Building and Oread Hotel
Celebrating Professor Mitscher’s 80th birthday and his contributions to the field of medicinal chemistry and to the University of Kansas
Part 1 of my LesFest recap can be read here.
The symposium to honor Les was held on Friday, May 13th in the beautiful new Pharmacy Building on West Campus. Dan Flynn chaired the morning session, which featured talks by me, Steven Djuric, and Dale Boger. Barbara Timmerman (University Distinguished Professor and Chair of the Department of Medicinal Chemistry), Ken Audus (Dean, School of Pharmacy), and Bernadette Gray-Little (Chancellor, University of Kansas) opened the proceedings with some warm, kind words about Les and his lasting contributions to the Department, School of Pharmacy, and University.
The Mitscher Symposium speakers (l–r): Dale Boger, Robert Fecik, Ashok Bhatia, George Ellestad, Les Mitscher, Dan Flynn, Gunda Georg, and Stevan Djuric.
Click on the picture to see more photos from the Mitscher Symposium.
I had the challenging task of giving the first scientific talk of the day, and chose to start my talk with some person reflections about Les and my time at Kansas. I’ll share some of those comments at the end of this post. I was feeling a bit under the weather and my voice was rough, but I thought the talk about some aspects our tubulysin project went very well. The feedback I received was overwhelmingly positive, and I got a lot of excellent suggestions and ideas from members of the audience.
Stevan Djuric from Abbott was up next, and he gave a very interesting talk on new chemistry technologies and methods he and his team have developed. It was a very insightful and thought-provoking presentation about the technological innovations taking place in industry. Stevan is a close friend of Les’ from their many years working together during Les’ consulting.
My postdoc mentor, Dale Boger (Scripps), closed out the morning session with great talk about the amazing chemistry developed for the total synthesis of Vinca alkaloids. This was an updated version of the talk he gave at last year’s National Medicinal Chemistry Symposium, and it included some new vinblastine analogs and biological data. It’s incredible work, and Dale always gives a fabulous presentation. Les hired Dale at Kansas while he was Chair, and Dale recounted some outstanding advice he received from Les while a junior faculty member.
Over lunch I had a enjoyable time catching up with my old friend Tim Caldwell, a former student of Gary Grunewald’s who is now at Deciphera Pharmaceuticals. The time passed quickly, and I had to get back to prepare for the afternoon session.
I had the pleasure of introducing the afternoon speakers, beginning with Dan Flynn, President and CEO of Deciphera Pharmaceuticals, who received his Ph.D. with Les in 1981. Dan’s had an amazing career in pharma, so it’s no surprise that he’s had incredible success with Deciphera, the company he founded in 2003. He presented the ingenious “switch control inhibitor” approach towards the design of kinase inhibitors, which has resulted in an Abl kinase inhibitor that entered a Phase I clinical trial last year. This is amazing work, and Dan had presented a version of this talk a couple months ago here at Minnesota.
George Ellestad was hired by Les at Lederle in 1964, and this launched his remarkable, nearly 40-year career at Lederle and Wyeth. He conducted seminal natural products chemistry through his career, including contributions that led to the development of tigecycline, a glycylcycline tetracycline antibiotic. George is also a Member of the American Chemical Society Division of Medicinal Chemistry Hall of Fame, in part for his ground-breaking work on the identification and mechanism of action of calicheamicin, an enediyne antitumor antibiotic. This lead to the development of Mylotarg, a calicheamicin–antibody conjugate, that was the first drug–antibody conjugate approved for clinical use. Since 2005 George has been an Adjunct Senior Research Chemist at Columbia University. In his talk, George gave a fascinating recount of the structure elucidation, mechanistic studies, and bioconjugate chemistry that ultimately led to the discovery of Mylotarg.
Ashok Bhatia from the Process R&D group at Abbott was up next. Ashok also received his Ph.D. with Les in 1981, and has had a very successful and productive career at Bouroughs–Wellcome and Abbott. Today he spoke about the development of a couple pilot-scale routes to an H3-receptor antagonist, which included some interesting metal-catalyzed cross-coupling chemistry. Process chemistry talks are always fascinating to me, and Ashok’s presentation was extremely insightful.
Although the end of a long day was approaching, it’s always a pleasure to hear about the latest work from Gunda Georg, Chair of Medicinal Chemistry at Minnesota. Les hired Gunda at Kansas in 1984, and we were fortunate to lure her here to Minnesota in 2007. Gunda also relayed advice she received from Les early in her career prior to delving into a two-part talk. The first part described the discovery of minnelide, a triptolide prodrug that is scheduled to begin a Phase I clinical trial later this year. In the second half, she presented enaminone methodology that been used for the total synthesis of tyloindicine alkaloids and analogs. Her talk ended a fantastic day of talks, and all presentations were very well-received.
At the conclusion of the talks, a poster session was held in the lobby of the Pharmacy Building. Twenty posters were presented, including ones by my students, Mike Peterson, Will Fiers, and Yang Li. The poster session was cut a little bit short due to the length of the oral presentations, but everyone stuck around to visit the posters for a while.
The festivities then moved over to the Oread Hotel for a banquet dinner. The food was among the best I’ve ever had at a banquet, and a social hour provided ample time to meet many people I hadn’t had a chance to visit with up to this point. After dinner, the highlight of the evening was a slide show by Les, during which he recounted many stories about his family, research, friends, and travel throughout his career. It was emotional at times, especially when talking about family, and the presentation was both heart-warming and inspirational. This was followed by some words from Les’ sons who talked about their views in growing up in the Mitscher household and how much Dad and Mom mean to them. It was a fitting end to an wonderful evening, and it was hard not to be overwhelmed by the outpouring of love and affection shown to Les by everyone. After everyone had left, my students and I visited with several of the KU students for a while before calling it a night.
Robert Fecik, Les Mitscher, and Pratik Devasthale at the Mitscher house.
Click on the picture to see more photos from the Mitscher Symposium.
The next day, Saturday, Les and his wife, Betty, hosted the out of town guests at their home for an informal open house around noon. It was a relaxed atmosphere, and it gave everyone the opportunity to visit with each other once more before departing Lawrence. There were simply too many great people I met and caught up with to mention everyone by name, but one personal highlight was finally meeting Pratik Devasthale. Pratik received his Ph.D. with Les, and I took over his thesis work on quinolone antimicrobials when I joined Les’ group. He has since gone on to do great work at BMS, most notably the discovery of muraglitazar (Pargluva), a dual alpha/gamma-PPAR agonist for type 2 diabetes that was submitted for marketing approval to the FDA but was ultimately never approved for a variety of factors. After giving my thanks and best wishes to Les and Betty, I picked up my students at the hotel and we hit the road for a rainy drive back to Minneapolis.
