Biomimetic Diversity Oriented Synthesis of Panepophenanthrin-like Molecules.

In the revolutionary age of high-throughput biology, novel genes and proteins are emerging quickly. In order to understand the biological relevance and function of these genes and proteins, and to determine their potential as targets for treating human disease, scientists need molecular tools to probe these systems.One of the best sources of well-known and new chemical tools is Nature, and such natural products have been instrumental in helping unravel complex biological mechanisms. Unfortunately, these molecules are often in short supply from the natural source, and chemists are required to synthesise these molecules from available starting materials. However, it is not always possible to make such compounds in sufficient quantity if they are too complex or require multi-step syntheses.Therefore the need for developing chemical synthesis-derived methods that allow rapid access to poly-functionalised, complex natural product-like molecules is growing constantly. This is largely because these small molecule-based compounds serve as smart, powerful tools both in understanding the roles and functions of emerging biological targets, and in validating their biological responses. One approach that chemists adopt to make natural-product like molecules is termed a biomimetic-synthesis. Biomimetic - from the Greek word bios , meaning life, and mimetic-the adjective for mimesis -- imitation or mimicry, is the application of methods and systems found in nature to the study and design of synthetic systems. This technology transfer is desirable because evolutionary pressure typically forces natural systems to become highly optimised and efficient. Thus, mimicking the way Nature makes natural products can sometimes facilitate access to complex structures that may otherwise require inconceivable conventional synthetic pathways. In this research project, we propose to make a library (many different) of complex natural product-like structures using a biomimetic approach. The molecules will be built using solid-phase techniques, which allow for the rapid purification of compounds by attaching them to a plastic bead that can be picked out of the reaction vessel. Once we have made lots of different molecules, we will test them against a range of cancer cells to determine if they have biological activity. This may help us discover new tools for studying the biological processes of cancer cells, or may even uncover potential new anti-cancer drugs.