Development of natural product-like compound library for drug discovery based on diversity-enhanced extracts

Natural products and their derivatives have been very useful in the search for biologically active compounds and for the development of new drugs because of their structural diversity. However, to retain their usefulness in the future, new approaches to increase the chemical diversity of such natural products must be developed. Diversity oriented synthesis has recently emerged as an efficient methodology to construct complex and diverse compounds from simple and similar precursors. Thus, through the combination of natural products chemistry and diversity-oriented synthesis, we propose a new approach, diversity-enhanced extracts, for increasing the diversity of natural product-like compounds. Diversity-enhanced extracts are prepared from chemical reactions that remodel molecular scaffolds directly on extracts of natural resources. The subsequent isolation of each compound produced from such reactions affords a diverse natural product-like library. We applied this method of diversification on several medicinal plants. From diversity-enhanced extracts of the medicinal plants, we obtained new and diverse sesquiterpenoids, indole alkaloids, meroterpenoids, and biaryls with some containing new molecular skeletons.