Institute Seminar - "Synthesis of Natural Product-Inspired Compounds for Molecular Discovery"

The talk explores recent advances in the Foley research group for synthesis and application of natural product-inspired compound libraries. This spans the development of new synthetic methodologies through to the rational design of lead compounds. The first part of the seminar details the development of synthetic strategies to prepare and modify bridged bicyclic compound libraries. A directed palladation approach for the heteroarylation of an oxabicyclic fragment will be described, adding to the growing reaction toolkit for three-dimensional fragment functionalisation. Our ongoing work investigating the generation and synthetic applications of underexplored bridged bicyclic alkynes to create unusual, fused pharmacophores will then be discussed. The second half of the talk focuses on the rational design of a selective chemical probe for the splicing-associated kinase CLK4 by systematic modification of quinine-derived inhibitors (quindoles). A newly obtained crystal structure of a lead compound bound to CLK4 will be revealed, providing new opportunities to further refine our inhibitor development. The seminar concludes with discussion of a recent method to completely iterate the aromatic ring in quinine, leading to the generation novel antimalarial compounds.