UV detection and fractionation is ubiquitous in flash chromatography. It is the default methodology used to detect and collect eluting compounds. Today’s flash chromatography systems offer UV-triggered fractionation on one, two, or a range of wavelengths in order to either increase fractionation specificity, yield, or increase sensitivity. In this post, I will discuss the value of incorporating fractionation based on a wavelength range and two selectable individual wavelengths.

For many chemists, flash chromatography with UV-triggered fractionation is part of their everyday workflow. Prior to flash chromatography, the reaction mixtures are either analyzed by TLC, analyzed by LC-MS, or both to ensure the targeted product has been synthesized. But, what if the reaction created a lot of by-products? How do you find your product in a sea of impurities? In this post, I will discuss how using a flash purification system with an in-line mass detector will simplify flash purification and isolate the target molecule or molecules. 

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!

From October 1st Biotage® Sfär columns are available and they appear automatically on the Selekt instrument. Learn more about Selekt and Sfär. If you run your Flash purification on Isolera® and you would like to start testing the new Sfär columns, there is an easy way of doing it. You can just follow the instructions below.

The synthesis of new chemical entities certainly has a high environmental cost due to the chemicals employed, especially in flash column chromatography, where large quantities of solvents are routinely used. The previous article in this series presented three strategies that can greatly reduce the environmental impact of your flash purifications: (1) purifying more product with less silica, and solvent, (2) making green chemistry work for you, such as changing to more environmentally friendly solvents, and (3) optimizing chromatography with more effective step gradients. Let’s look at how new developments in column design, simplifications in step gradients, and support from a leader in flash column chromatography can help in making your operation greener.

 

As we saw in a previous article, the most critical and time-consuming part of organic chemistry synthesis is the purification step. Running a column, testing the resulting fraction, and maybe re-running columns takes too much time – time you could use to prepare reactions or research new chemistries. What if your laboratory equipment made it easier for you to focus on amazing khemistry? Let’s find out what is possible with the latest in automated flash column chromatography systems. 

Discovery chemistry labs synthesizing new molecular entities (NMEs) are under pressure to improve their productivity. Optimizing the design-make-test-analyze (DMTA) cycle in the discovery process means ensuring the slow, iterative make step in the process is faster, more predictable and less time-consuming. Although both synthesis and purification in the make step are regarded as most challenging, it is purification that is the most critical aspect of the chemists work. Chemists cannot afford to spend the majority of their time and energy purifying target molecules as this slows down the discovery chemistry process. Effective and reliable purification tools and technologies are critical to the step-change needed in the make cycle. Let’s see how this is possible by partnering with reliable vendors.

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 Biotage

The 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®.

Sfär Stands for Spherical, Biotage® Stands for Quality 

Biotage developed and introduced pre-packed columns for flash purification in 1994. Today our broad selection of columns enables professionals to choose the solution which best suits their purification needs.

Sfär is the Swedish word for "sphere", and the name of our columns reflects the fact that we have made spherical silica a standard due to its higher surface area and higher loading capacity. Reliable and flexible, Biotage® Sfär columns deliver larger loading capacities, tighter elution bands and purer fractions than traditional flash columns.
Biotage® Sfär is a complete portfolio of flash columns, available in a large variety of sizes from 5g to 350 g and in a range of media types, so you can purify milligrams to multi-grams of your valuable compounds quickly and easily.

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.

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.

Our recent survey of organic synthetic chemists showed that more than half of you feel that the most enjoyable aspect of your work is researching new chemistries, while 33% told us that preparing reactions was the best part of your day. Purifying products and writing up came in at distant 3rd and 4th places, and no one enjoyed doing work up. Sounds familiar? If you want to find out more about how to bring fun back into your chemistry then read on.

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