Nature can serve as an excellent source of novel biologically active compounds. Unfortunately, a large number of known active compounds are often encountered during the search for novel chemistries. Therefore, early stage identification, and determination of novelty is of critical concern to natural product chemists. We have designed a screening process utilizing a single quadrupole LC/MS system to efficiently distinguish novel compounds from known compounds in crude biologically active extracts. This "dereplication" process is accomplished by chromatographing an extract on a LC column, diverting 95% of the eluent to a 96 well plate, and directing the remainder of the eluent to the MS for spectral analysis. Bioassay of the 96 well plate contents localizes the biologically active compounds, which are then structurally interrogated using MS, accurate MS, accurate MS/MS, and MSn. These data are often sufficient to allow identification of the active compounds from the initial small scale extract, avoiding costly sample recollection or refermentation. (C) 2003 American Chemical Society.

[reaction: see text] We present two new diffusion-edited NMR experiments, improved DECODES and HETDECODES, that sort the constituents in a mixture by their individual diffusion coefficients. These experiments should allow the partial NMR spectral assignment and cursory structure elucidation of compounds in a complex mixture as an aid in the dereplication of known or nuisance compounds.