Upon returning to the Boston area after a number of years away, I was very much looking forward to attending The Northeastern Section of the American Chemical Society (NESACS)’s Advances in Chemical Sciences “Bench to Plant” Symposium for the first time. Held in Cambridge on October 22, about 100 scientists from the local area gathered for the one day Symposium focusing on Process R&D Chemistry, Organic Synthesis, and New Synthetic Methodology.
Some highlights of the top-notch presentations included:
- Brian Stoltz from California Institute of Technology (Pasadena, CA) gave an overview on how the enantioselective Tsuji allylation can be used to build complex natural products
- Adam Looker from Vertex Pharmaceutical (Cambridge, MA) showed the value of using real time measurements based on RC1e reaction calorimetry, ReactIR™, and FBRM®, to improve process understanding, as well as to enhance the productivity and process safety of chemical and crystallization processes. One of the case studies demonstrated how ReactIR™ was used to troubleshoot a nitro reduction step in the middle of a scale-up campaign. The intermediate hydroxylamine was detected in real time at 3310cm-1 and its concentration could also be correlated to heat data collected with an RC1e. The powerful combination of heat (RC1e) and FTIR (ReactIR™) measurements were used to identify an optimum “dual-metal” catalyst (Pt/V CF-1082 from Evonik) that minimizes the formation of the intermediate hydroxylamine. On the process side, RC1e heat flow was used to study the impact of stirring speed on reaction rate as well as detect hydrogenation starvation regime. Finally, FBRM® and RC1e heat flow were used to improve the conditions of the final isolation through better understanding of supersaturation conditions and better control of nucleation. 965 Kg of final product (4 batches) were obtained in excellent purity and 87% yield. A long time advocate of real time monitoring technologies, Ben Littler (Vertex Pharmaceuticals, San Diego, CA), was involved in this project. Since I am convinced of the value of real time measurements and process knowledge to design better, greener, safer synthetic and biosynthetic routes to Active Pharmaceutical Ingredients (APIs), I was extremely impressed with Adam’s talk. Although I promote the same technologically-oriented approach whenever possible by giving presentations at major conferences, the testimonial Adam gave at NESACS largely surpasses what I have seen or given myself before.
- Richard Pariza from Cedarburg Hauser Pharmaceuticals (Grafton, WI) and OncQuest, Inc. (Zion, IL) admirably combined humor and science to convince us of the importance of vitamin D and the hazards of vitamin D deficiency. Richard then described the quest for vitamin D analogs as a fascinating adventure.
- Joseph M. Fortunak from Howard University took us through the difficult challenges of developing and commercializing drugs for neglected diseases as well as affordable drugs for the developing world. The team creativity and hard work have made anti-HIV Tenofovir and Efavirenz affordable to a large majority of countries.
- Steve Weissman from CoNCERT Pharmaceuticals gave an impressive account on the use of Design of Experiments (DoE) as a process optimization tool. He walked us through five different case studies highlighting the value of DoE versus the traditional one variable at a time (OVM) approach. Some of the experimental plans were conducted under HTS conditions in 96 well plates (1mL scale). Various software packages were used, including MODDE Umetrics and Design Expert. Thanks in part to this approach, Merck & Co. and Codexis received the 2010 Greener Reaction Conditions Award for the greener manufacturing of Sitagliptin enabled by an evolved transaminase.
- Eric Bercot from Amgen (Thousand Oaks, CA) delivered a presentation on the discovery and development of efficient approaches to chiral drug targets.
Although this was only the second time for this event, I found the NESACS Symposium very worthwhile. The exhibit was worthwhile although finding the time was a little bit challenging. There were about 15 exhibitors representing mostly CRO/CMO (Johnson Matthey, Pharmacore, Strem Chemicals, PCI synthesis, Wilmington Pharma Tech, Adesis, etc.), as well as instrument companies (Uniqsis, Gilson, Chemglass, etc.).
Overall, I was impressed by the quality of the organization: Thanks to Don Walker (Biogen, Cambridge, MA), Symposium Committee Chair, and his colleagues! and the affordability of the conference (only $50). For myself and other participants, it was also a pleasure to get a chance to catch up with colleagues and friends from local life science companies.