The recently reported and growing epidemic known as COVID-19 sounds terrifying. We still know so little about the disease, such as how it’s transmitted, whether it’s airborne, how deadly it is, and the short- and long-term health effects of what seems like no normal cold virus. For now, because so much about the virus is uncertain and local universities are shutting down in-person activities, we’re taking the unprecedented step of halting in-person research. Thus, the progress we’ve made on the total synthesis of clavatadine C, D, and E will have to wait for a while. We hope to resume research in a month or so depending on how long the pandemic lasts. There’s talk about developing a vaccine, but that could take years. Are we in for a long, dark period of our lives, or will this all blow over in short order? Who knows?
Congratulations to UVU graduates Michael Davenport, Jordan Dickson, and Matthew Johnson! Each earned their first peer-reviewed publication in the Journal of Natural Products. We report the first total synthesis of clavatadine B, a natural inhibitor of human blood coagulation factor XIa. Though it is not as potent as the clavatadine A congener, its synthesis was achieved using a similar direct, early-stage guanidinylation approach. The total synthesis originated from the same dibrominated precursor that was used to make clavatadine A, which made the total synthesis four-steps long. It is six steps from commercially available materials.
Read our paper here: Total Synthesis of Clavatadine B
With three abstracts submitted for Spring and Summer 2020 conferences, it looks like it’s going to be an active year for our group. Specifically, we submitted an abstract to give an oral presentation at the 2020 Spring ACS meeting, which was just accepted! Steve Chamberland will give the talk, which will focus the adventure and lessons learned on the path to our recently completed total synthesis of clavatadine B. This summer, he plans to give two talks at the Biennial Conference on Chemistry Education, the BCCE, which will be held at Oregon State University. There, we hope to meet up with two Chamberland group alumni, Jacob Buchanan and Chris Malmberg. Jacob recently finished his Ph.D. at Oregon State and is now working in industry and Chris is in the final stretch of his Ph.D. journey. Dr. Chamberland’s talks will focus on the Chemistry Cornerstone courses he developed at UVU and an in-class activity involving the seminal (15-step!!!) total synthesis of (+)-ryanodol by Caltech Professor Sarah Reisman and co-workers. This class discussion in Chemistry 2320 (Organic Chemistry II) normally falls during Women’s History Month, and highlights not just the work of a female chemist, but the work of one of the titans of modern synthetic organic chemistry.
This summer Steve attended the Biennial Conference on Chemistry Education (BCCE), which was held at the University of Notre Dame in South Bend, Indiana, as well as the fall national meeting of the American Chemical Society in Boston. He presented three talks at those conferences about recent metacognition research in organic chemistry as well as a classroom demonstration. The presentation titles are “The Metacognitive Exam Tool to Help You Learn (METHYL) project for sophomore organic chemistry,” and “Creating CSI experts in NMR analysis: an engaged, group-inquiry exercise in spectroscopy.”
Traveling to Boston for the ACS meeting offered an opportunity to join a T. Ross Kelly research group alumni reunion from Boston College. Ross was Steve’s undergraduate research mentor, and is in the middle-left of the picture. Twenty years ago, Steve completed the first total synthesis of luotonin A, a pyrroloquinazolinoquinoline natural product, with Ross and post-doc Rich Silva!
Since then, the BC men’s ice hockey team won a few national championships, and it was nice to see the banners hanging from the rafters in Conte Forum.
In addition, Steve’s Ph.D. advisor, NYU Professor Keith A. Woerpel (formerly of UC Irvine), was awarded a prestigious ACS Cope Scholar Award for his explorations of stereoselective reactions involving oxocarbenium ions. The X-ray crystal structure of an axially-substituted six-membered ring dioxocarbenium ion from Steve’s 2005 JACS paper was featured in the award address. It was great to catch up with a few group alumni from the early 2000s.
This April, albeit four years later than expected, Steve was awarded tenure with promotion to the rank of associate professor. It becomes official on July 1, which is when he plans to exhale for the first time in ten years. He couldn’t have navigated the extreme ups and downs of the process without his dear wife, pictured below at the tenure recognition dinner in April.
Congratulations to group members Michael Davenport, Jordan Dickson, and Matthew Johnson for their accepted poster presentation at the 2018 Spring National Meeting of the American Chemical Society in the Big Easy. Their poster titled “Total synthesis of clavatadine B by direct, early stage guanidinylation” was selected for the Monday night Sci-Mix session. Their effort to complete this ambitious total synthesis is commendable. Consider visiting their poster and asking them tough questions about the project. Look out for our submitted manuscript soon.
This weekend, I had the opportunity to attend a workshop sponsored by the Council on Undergraduate Research. Amply titled “Beginning a Research Program in the Natural Sciences at a Predominantly Undergraduate Institution Institute,” this forum welcomed a group of promising young research advisors to Washington, D.C. Led by several experienced facilitators, groups of faculty met to discuss such topics as advocating with administrators, building a cohesive group of research students, techniques to run a lab including time and resource management, and where to find grants to support research. I also had several opportunities to network, which usually puts me way out of my comfort zone. My breakout group was led by University of Nebraska-Kearney organic chemist Hector Palencia. He’s built a strong continuity of 3-4 students per year and has been externally funded, which enabled him to provide salient advice that we can apply to our research program.
Perhaps the most potent resource will be CURChem, a site built to connect and provide resources and encouragement to PUI researchers in Chemistry. One of the site’s premier contributors, Muhlenberg College’s own Keri Colabroy, introduced us to the student research contract, the electronic notebook LabArchives, and Slack, a social networking app designed to connect her to her research group and promote accountability for progress. I’ve set up Slack and plan to try out LabArchives; however, I’m skeptical as to how structures and pictures (e.g., TLC plates) can be drawn into the program. The great advantage is the ability to post videos and have a searchable archive of experimentation in the group over time. Now, I just have to find a student willing to transcribe eight years worth of paper research notebooks into LabArchives. Hmmm…
I was grateful for this opportunity, and had some creative time to plan out what I’m going to do when I return to campus, what I plan to accomplish before the end of the semester, and what I’m going to do this academic year.
One of my major professional weaknesses is my inability to delegate important but ancillary tasks to others. I think I can and should do it all myself, and that whatever I delegate will not be done as well, as quickly, or as foolproof as I can do it. I’ve got to abandon that line of thinking. I must abandon that thought pattern. My research students are eager and capable of helping, and probably can accomplish what I ask of them if I provide sufficient direction and follow-through. Leveraging my team’s time and skills to handle the little things would free me up to work on the big-picture things, such as grant writing, coming up with new ideas to drive the program forward, maintaining collaborations, and ensuring the continuity of the group for the next year(s).
Other than catching up on grading, here’s what I plan to do when I return to campus and for the last month of the semester: reboot our weekly writing accountability group, finally get my research lab all set up, get our NMR spectrometer connected to the campus network and write a training manual, train my students to begin working in the lab, plan a day/time for weekly group meetings, set up LabArchives and begin posting to it, organize and update my references once and for all and import them into Zotero, and get my very eager students to begin doing chemistry.
Research-wise, here’s what I plan to do through the Christmas break and at the beginning of spring semester: complete and submit my NIH R-15 AREA grant proposal, apply for a $5000 research grant from the American Society of Pharmacognosy, have my students apply for internal funds, and start assembling experiments and completing curriculum paperwork for an upper-division NMR-based synthesis lab/lecture course. I must also get the Metacognition project off the ground with my internal collaborators, especially because I’m teaching two sections of Organic Chemistry I in the Spring. To do that, I must get IRB approval, finalize my assessment documents, deploy them, and complete an internal grant proposal that will enable me to hire and train student graders.
I can and will do this. Please keep me accountable readers!
Awhile back, I thought the community of undergraduate research mentors, like myself, could benefit from an online network. The main purpose would be to have a database of true peers, from peer institutions, to collaborate with, to recommend as journal article and grant proposal reviewers, and to network with online and at conferences. This idea was inspired by organiclinks.net and chembiolinks.net, which have united faculty and students from doctoral institutions for years. It now exists. I hope this is the start of something promising, but this is the most ambitious endeavor I’ve undertaken. Let’s see what happens.
Visit organiclinkspui.net, and see for yourself.
The American Society of Pharmacognosy (ASP) bestowed the Jack L. Beal Award to Dr. Stephen Chamberland as corresponding author of the paper “Total Synthesis of Clavatadine A.” This paper was published in the Journal of Natural Products in 2015. Jointly overseen by the American Chemical Society and the American Society of Pharmacognosy, the Journal of Natural Products “invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained (http://pubs.acs.org/page/jnprdf/about.html).”
“In 2001, the Foundation Board of the American Society of Pharmacognosy began a new initiative as a result of the Arthur E. Schwarting and Jack L. Beal Awards for best papers in the Journal of Natural Products. In this manner, two former distinguished editors of the journal are fondly remembered. The Schwarting Award is open to all papers published in the journal within a given year (either in print or electronically). In turn, the Beal Award is awarded to younger investigators [i.e., persons within 12 years of receiving their Ph.D. degree or within 10 years of gaining their first professional appointment (e.g., Assistant Professor or equivalent position in industry or government)]. A two-tier process was used to determine the winners for papers published in J. Nat. Prod. every year. The journal editors nominate eight papers for the Schwarting Award and four paper for the Beal Award, and the ASP President appointed an ad hoc committee to make the final selections (http://www.pharmacognosy.us/grants-and-awards/grants-and-awards-archive/schwarting-beal-awards/).”
I am profoundly humbled, honored, and thrilled that our manuscript was chosen from among many deserving submissions to receive the prestigious Jack L. Beal Award. I thank the Journal of Natural Products Editorial Staff and the ASP ad hoc committee members for their distinguished service and for recognizing our work. Without substantial contributions from undergraduate student co-authors Stephanie J. Conn, Shannon M. Huffman (Vreeland), and Alexandra N. Wexler, the first total synthesis of the Factor XIa inhibitor clavatadine A would not have been possible. Our efforts engendered a synthesis that is simple, robust, and, most importantly, repeatable. Such recognition of our work is encouragement that my students and I may have something worthwhile to contribute to science and to human health.
We are working to extend this approach to prepare a reversible Factor XIa inhibitor, and are especially intrigued by the potential that clavatadine A derivatives might have to treat coagulation disorders. This proposed work will build upon our successful route to clavatadine A and aminoguanidine-containing natural products, and will be the subject of a forthcoming CAREER proposal to the National Science Foundation. I especially want to thank our Australian collaborators, most notably Distinguished Professor Dr. Ron Quinn and Dr. Rebecca H. Pouwer, for providing the biological assay data that helped to confirm the structure of our synthetic clavatadine A and to authenticate its inhibitory activity.