Dry loading crude samples for flash purification typically works better than liquid loading, especially for challenging purifications. In this post, I discuss how the ratio of crude sample to dry load sorbent impacts purification performance.
Learn more about how to get in control of your Flash Purification.With Biotage® Selekt and Sfär chemists can be in full control of Flash Purification.
On December 6th, 2018, Bob Bickler, Senior Technical Specialist, recorded a webinar on How To Be Successful with Flash Chromatography. To learn more, read the description below as well as watch the recording!
With synthesizing new molecular entities (NMEs) our mission in life as chemists, we are innovators, creators even. In drug discovery research, these NMEs stand a good chance of becoming a cure for a major illness or disease. Few roles in life provide such opportunity for making a positive impact on society as does being a medicinal chemist. It is no wonder that we are so emotionally attached and protective of the targets we create, almost in a parental way. This is why we need to carefully manage every step of the NME synthetic process. The question is, how can we ensure that we have full control over one of the most important, yet least enjoyable steps in the process – purification?
I think that the phrase ‘creative productivity’ captures the essence of an organic chemist’s work. It’s not about the number of new molecules produced per day at all. Creative organic chemists have much more in common with prolific artists and craftspeople. Prolific chemists are relentless discoverers of synthetic pathways that result in a stream of new molecules in, for example, pharmaceutical research. Being prolific involves dealing with the complexities of synthetic pathways, completing projects, and strategizing the next steps once the SAR study results are in. Increasing productivity involves knowledge, and applying it, using the right tools.
Konfidence With a Capital "K", That's Why I Selekt BiotageThe new Biotage® Selekt Flash Purification System is a system you can use with Konfidence. Purification is a fundamental step in discovery research and, as pioneers of automated flash purification, Biotage® is your ideal partner. Our core philosophies of Quality, Reliability and Environmentalism are drawn from our Swedish heritage. Our smart and intuitive design comes from our knowledge of what our customers need each day. You can see why our customers have “Konfidence” with a capital “ K” in our brand.When it comes to purification there are five reasons to Selekt Biotage®.
Pharmaceutical researchers feel real pressure to increase their R&D productivity by ‘doing more with less’. Despite having limited internal resources and specialized expertise, discovery chemistry research labs are expected to be increasingly effective and efficient, and deliver drug targets faster to advance projects rapidly. However, a lack of effective tools and technologies results in low efficiency workflows, with slow and laborious lead generation and optimization as a result. To boost productivity, the iterative cycle of design-make-test-analyze (DMTA) must move to a ‘best-practices’ state to become faster, more predictable and less time-consuming. A key factor is availability of reliable purification systems from dependable vendors.
Isn’t amazing chemistry what you want to do every day? Don’t you strive for white crystalline final products? But things get in the way, such as other priorities, endless emails and frequent interruptions to your synthetic flow. Not to mention the challenges of designing new synthetic strategies, creating what could be the world’s most impactful new molecular entity. Finding the right reaction, the right reagents. Finding a way to get around yet another dead end. But those challenges are why you got into chemistry in the first place, right? After all, if it was easy, anyone could do it and you’re not just anyone. So let’s look at a few things that can put the fun back into chemistry.
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.