High-throughput natural products chemistry: Is it possible?

Sequoia Sciences identifies novel chemistry from its library of structurally diverse small molecules isolated from plants. The proprietary design of this library allows for the screening of these compounds at optimal HTS concentrations without non-drug-like interferences. Sequoia built this analytical process such that rapid isolation and structure elucidation of active compounds could be accomplished. Using the extremely sensitive CapNMR probe, structure elucidation of active compounds is completed on samples of limited mass. Relative to synthetic library HTS, the question remains, is it really high-throughput natural products chemistry? Can the rate limiting step, structure elucidation process, be a higher throughput process? The scientific strategy that Sequoia employs in order to rapidly uncover the chemical diversity contained in plant natural products will be outlined. This presentation will expand upon the ground breaking CapNMR probe by describing the MultiSampleTM CapNMR probe. This advanced capillary NMR probe acquires complete NMR data sets on two samples simultaneously. The Protasis Dual SampleTM Probe (DSP) has now extended the high-throughput process to include NMR data acquisition. This talk outlines sample loading and data acquisition ease of the DSP probe, presenting data on biologically active compounds isolated from preparative HPLC fractions from Sequoia's library. By essentially achieving the same performance for each sample as achieved using a single sample CapNMR probe, the DSP probe provides a doubling of throughput in 1D proton as well as all gradient 2D experiments. Sequoia's inclusion of the DSP probe compliments its current platform technologies for high-throughput natural products research.