Natural product chemistry has traditionally been a long and time-consuming process for drug discovery research. From extraction, isolation and purification to structure elucidation, active fraction identification is a real challenge in creating value for today’s HTS programs in large pharmaceutical companies. Sequoia Sciences has developed rugged HPLC extraction and isolation methodologies for purified natural product chromatographic fractions that fit right into today’s HTS screening platforms. Sequoia has also overcome the barrier of structure elucidation on minute quantities, i.e. microgram quantities of active natural product compounds, a necessary requirement in satisfying the “H” criteria in high-throughput screening programs. A successful natural product discovery program in today’s drug discovery process must have all of these elements of the isolation process rapidly completed and validated as well as rapid structure elucidation to follow up on leads. This must be done on scales approaching traditional screening quantities.

With the introduction of the CapNMR^R probe, new opportunities were created to take the sample requirements down to the microgram scale. Sequoia has previously published papers on its complete process as well as several papers on the use of the CapNMRR probe in working on mass limited samples. In our quest to become better and faster in providing the structure of an active unknown to the drug discovery process, Sequoia has created addition speed and value with the addition of an FT/MS to the process. For full NMR data set acquisitions on compounds from challenging HPLC isolations at the single digit microgram scale, utilizing minimal NMR data with high resolution MS data, Sequoia is able to accelerate the discovery of active and novel compounds from natural product sources.

Data will be presented demonstrating routine acquisition of proton and COSY on 1-10 micrograms of material originating from complex HPLC separations of natural products. With the FT/MS and its SORI technique, Sequoia has created a new way for HPLC chemists and NMR spectroscopists to uncover unknown structures at very low amounts without the need to recollect and scale up. By eliminating this process and using modern instrumentation in an intelligent and creative way, natural product research can realize its full potential in drug discovery.