Novel bioisosteres for medicinal chemistry

Description

To build new medicines, agrichemicals, and advanced materials, synthetic chemists combine building blocks with defined shape and size. The largest proportion of available building blocks are flat (achiral) aromatic compounds, which are readily available, well-studied and undergo a wide range of useful reactions. In a three-dimensional world, these flat building blocks severely constrain chemists’ ability to invent new life-changing molecules and materials. Access to building blocks that possess all the benefits of aromatic compounds, but that also incorporate three-dimensional shape (and chirality) is a pressing unmet need. The development of new molecular systems typically involves altering the groups attached to the flat aromatic core of privileged molecular fragments (peripheral substitution). However, the use of internal substitution to tune structural, electronic and chiral properties of molecules is unexplored (Fig 1.). This project will explore both the chemical reactivity of these types of compounds as well as their potential to be incorporated into drug molecules as isosteres of naphthalene.