Synthetic organic chemistry is the genesis of new pharmaceutical and commercial chemical products. In short, it is based on the idea that two or more carbon-based compounds can be forced to react using heat, or other energy source, to create a new, novel product – but this we already know.
Many microwave assisted organic synthesis (MAOS) reactions use polar solvents such as alcohols, DMF, DMSO, because they absorb and transfer microwave energy very efficiently. However, the downside of using polar, microwave absorbing solvents is that they can interfere with normal-phase flash chromatography.
In this post, I discuss why dry loading can be advantageous when purifying polar-solvated reaction mixtures.
Flash chromatography is a chemical separation technique used to purify chemical mixtures. Because it is a purification technology, the process is also referred to as flash purification.
"With using the entire workflow, we're able to do things more efficiently," stated Dr. Justin Anglin during our interview in February at the Center for Drug Discovery at Baylor College of Medicine. Keep reading to find out more about how his role as the Director helped influence their state-of-the-art lab to include a full suite of Biotage products.
New drug substances, the result of more than a decade of pharmaceutical research and development, have revolutionized society by saving lives, increasing life-spans, reducing suffering, avoiding surgery, and shortening hospital stays. New breakthroughs in the treatment of non-communicable diseases mean that drug substances are in a constant state of high demand, making the pharmaceutical industry one of the most innovative of industries on the globe. Why then, do so few drugs come to market? It turns out that a key factor is providing drug discovery chemists with tools such as automated flash chromatography to ensure that they can be confident in delivering target compounds in a timely fashion.
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
Creative productivity is the ability to find innovative ways to keep projects moving forward, including finding a way around the roadblocks that will inevitably show up as you go. So the real measure of productivity is not in molecules per day, but in your ability to find the synthetic pathway. Instrument manufacturers tend to want to tell you about the latest user-friendly ultra-fast instrument. Faster is nicer, but if you can cut 30 seconds off a column chromatography step, what does it matter when the reaction refluxed overnight and the reaction didn’t work? The thing is, many of the reliable techniques you apply to your organic chemistry work are considered unchangeable. There may be a better way, but that takes time and feels risky. So, you continue on, using what you learned as far back as college chemistry.
Organic reactions are generally inefficient, which means that crude reaction mixtures require work-up and purification to remove by-products and unreacted starting materials and/or catalysts. The goal in pharmaceutical research is to isolate the target compound with required purity and yield to be able to progress to the next synthetic sequence or biological testing with confidence. But the process of purification is viewed by synthetic chemists as a ‘means-to-an-end’ and the more rapidly and reliably the purification step can be performed the better. Easy enough to state, but hard to achieve when you need to be certain of purity and yield in a single, rapid purification attempt. As we will see here, flash column chromatography can help you achieve this.
First, join me on a flashback to my past as a discovery chemist just fresh out of grad school and eager to make a difference in pharmaceutical research. I was advised by my boss to model my behavior after a colleague and labmate with a reputation of being highly productive and successful. I was also informed that ‘chemist productivity’ was measured by 1) the number of compounds (of sufficient quantity and quality) he/she registered in the company’s database and 2) meeting project milestones.