Most of the strategies to guide the discovery process of new bioactive natural products are time-consuming. Therefore, we developed a new strategy to accelerate this discovery process. Combining differential analysis of 2D-NMR spectra to obtain a pharmacophoric fingerprint, with HPLC-DAD-MS-SPE-NMR hyphenated technique and a bioactivity assay, this strategy led to the reliable structural identification of the activity-bearing compound. The proof of principle was performed to identify the oxygenated diterpene eleganolone known as the antimalarial active principle of the brown algae Bifurcaria bifurcata organic extract. This new strategy called “pharmacophoric deconvolution” was compared to the classical “bioguided fractionation”. Both strategies led to the identification of eleganolone but the pharmacophoric deconvolution approach was three times faster and needed less starting raw material than the classical strategy. Consequently, it constitutes an efficient strategy for the wide field of bioactive natural product research. It is clear that the combination of NMR fingerprint with the HPLC-DAD-MS-SPE-NMR offers great potential for the new bioactive natural products research.