OK. We get it. You aren’t a molecule factory. Creating the right target molecule as soon as possible in order to keep your pharmaceutical research project moving isn’t easy or routine. Frankly, organic chemistry is hard and unpredictable. As Professor Gilbert Stork said, “Unless the molecule is very simple, it is not possible to go into the lab and make it within a short period of time.” His ‘Rule of Seven’ meant that, “however long you think a synthesis will take, multiply it by seven”.1
So making an organic molecule for the first time is a challenge that is very rewarding but may also be very frustrating. You don’t want to spend time fine-tuning tools such as flash column chromatography in your laboratory. Your focus should be on the new structure. In this series of articles we will look at key factors that affect productivity and how to smoothly progress along the synthetic pathway and quickly get to the finish line.
Reduce the pain of solvent removal
As an organic chemist, you can spend 70–80% of your time working up and purifying compounds that you have just synthesized. This takes time for a lot of reasons. Often just the act of removing solvent using a rotary evaporator means that you will be standing and monitoring conditions, trying to avoid bumping. This is especially true when you have to switch from normal to reversed phase chromatography. Minimizing solvent use will reduce the amount of time needed to evaporate and is also a great example of how going green will also boost productivity.
Automation makes you more productive
When you are running an automated chromatography system it is tempting to stand by the control screen throughout the run, adjusting chromatographic conditions in an effort to improve the separation of your valuable compound mixture. Why? Because when running a new compound mixture for the first time, you feel that the result of the separation is unpredictable, so the most productive thing to do is to be on standby to correct and adjust based on your experience.
If an automated system is set up correctly then you don’t have to be on standby because the results you obtain will be predictable. It’s about confidence and combining the right tools with the right knowledge, so that it is not just possible but natural to set up a separation and walk away, confident that the system will consistently deliver successful separations.
The idea of having to purify new molecular entities with as-yet undetermined properties brings many challenges to mind. However, by focusing on separating a mixture more successfully with higher resolution using reproducible column chromatography methods you can prepare more pure compounds, more often, and on the first try.
Achieve real speed
Speed is only a benefit when it is paired with reliable and reproducible performance. Productivity means when the purification process is completed, you will have pure compound ready to take to the next step. Speed without reliability doesn’t help productivity, because there’s nothing worse than your instrument crashing in the middle of a separation, losing a sample, or having to postpone everything while waiting for service.
Creative ways to improve productivity
One of the big obstacles to boosting productivity is finding the best way forward when problems arise. Solving these problems can demand a lot of creativity, and this will be something we will look at in the next article in this series.