PDR-Chiral (www.pdr-chiralcom) is using chiral chromatography to provide chiral separations as early as possible in compound development. The goal, according to Gary Yanik, president and CEO, is to work smarter, using as little labor as possible to achieve separations. That requires automation.
"Ten years ago," Yanik says, "chromatography was a bad word as far as synthesis chemists were concerned. They wanted to brew molecules without chromatography.
"Now they're realizing that some of the steps in processing can be accomplished by chromatography much more economically than by basic chemistry. Earlier involvement equals better efficiency," Yanik emphasizes. Therefore, "Chromatography is being used more creatively, and earlier in products."
"The way you have been doing it isn't necessarily the way you should be doing it," Yanik stresses. In his presentation at "Chirality 2005", he emphasized the need to configure systems for full automation, tying together the appropriate solvent mixers, column selectors, injectors, detectors, collectors, and software.
Beyond that, however, researchers need to take the time to optimize their methods, techniques, and procedures, writing them down, so they are computercontrolled and self-maintaining. "People don't do this often enough," he says.
"People need to develop a flow-chart mentality for processing compounds in the minimum amount of time, but they don't see it as a flow of work and so haven't developed a system or procedure" to maximize workflow.
Yanik says for example,"they may do a literature search. But in 24 hours we can screen against compounds and probably learn more than they've found in the literature, because these compounds have just been created. They, in comparison, are researching similarities. That's not necessarily productive."
In terms of increasing productivity, he recommends screening using gradients for increased speeds and varying the columns, but keeping the eluent the same, with sequences to proceed in increasing or decreasing miscibility values, including wash and equilibrate methods at the end. "That's important," he says, "because if you don't pay attention, the solvents won't dissolve in each other."
In prep purification, Yanik recommends making a large number of injections to achieve low-risk, high-purity separations. The goal, is to select the highest loading possible while maintaining baseline separation and the shortest cycle time possible that can avoid impurities, .
Supercritical fluid chromatography (SFC) is a new technology that is gaining popularity and can help reduce evaporation volume. "Normally, researchers use hexane in solution, but by using SFC, we can replace the hexane with carbon dioxide and alcohol, which is safer for the environment. When you finish a job, it's already evaporated, and it is easier to recover the compound," Yanik says.
PDR-Chiral's latest software products include the Auto MDS for method development and AutoPrep for purification. These modules can be integrated into other systems, which then can be operated through PDR-Chiral software for 24/7 operation.