Chemical Diversification of Natural Product Extracts

Abstract

By virtue of their sustained success as sources of lead compounds, natural products are recognized as privileged starting points in structural space for library development. Compared with synthetic compounds, natural products have distinguishing structural properties. They differentiate in the number of chiral centers, the degree of saturation, the presence of aromatic rings, and the number of heteroatoms. Natural products also include a significant proportion of recurring molecular scaffolds that have been refined over the long process of evolution.In this review, we will discuss the research aimed at preparing chemically engineered extracts (CEEs) through chemical diversification of natural products mixtures. The approach relies on the power of numbers, that is, in the chemical alteration of a sizable fraction of the starting complex mixture. Major changes in composition can be achieved through the chemical transformation of reactive molecular fragments that are found in most natural products. If such fragments are common enough, their transformation represents an entry point for chemically altering a high proportion of the components of crude natural extracts.To date different reactions have been used to incorporate nitrogen, sulfur, bromine, fluorine, etc. The resulting CEEs had different composition and biomolecular properties than their natural progenitors and have been the sources for of semisynthetic bioactive compounds such as: a β-glucosidase inhibitor from a CEE prepared by reaction with benzenesulfonyl chloride, antifungal o antiamyloidogenic pyrazoles from a CEEs prepared by reaction with hydrazine, an acetylcholinesterase inhibitor and a xanthine oxidase inhibitor from CEEs prepared through bromination, a tyrosinase inhibitor from a CEE prepared through fluorination, etc. These examples illustrate how biological activity can be generated through chemical diversification of natural product mixtures.