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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
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Microscale purification in support of high-throughput medicinal chemistry
Chandan L Barhate1, Andrew F Donnell2, Merrill Davies1
1Separation and Analysis Technology Team, Bristol Myers Squibb, Lawrenceville, NJ, USA. chandan.barhate@bms.com.
Chemical Communications (Cambridge, England)
|October 5, 2021
Summary
This study presents a high-throughput purification workflow for microscale synthesis in pharmaceutical discovery. The optimized system efficiently purifies compounds, reducing costs and timelines in drug development.
Area of Science:
- Pharmaceutical Sciences
- Analytical Chemistry
- Chemical Engineering
Background:
- Assay miniaturization is advancing pharmaceutical discovery.
- Reducing synthesis scale lowers material consumption and experimental costs.
- Efficient compound isolation and purification are crucial for library synthesis.
Purpose of the Study:
- To describe a high-throughput purification workflow for microscale library synthesis.
- To enable efficient purification of compounds synthesized at the 1-5 μmol scale.
- To support cost-effective and time-efficient drug discovery processes.
Main Methods:
- Development of an optimized microscale purification system.
- Implementation of a high-throughput workflow for 384-well plates.
- Focus on instrument optimization and critical purification parameters.
Main Results:
- The system routinely purifies 384-well reaction plates.
- Achieved an analysis time of 4 minutes per sample.
- Demonstrated successful library purification with optimized parameters.
Conclusions:
- The developed workflow supports efficient microscale library synthesis.
- Miniaturized purification reduces costs and timelines in pharmaceutical research.
- This approach enhances the feasibility of large-scale compound library generation.
