Expanding Chemical Space via Microbial Biocatalysis Late-stage Functionalization

Presented at: 29th symposium on Medicinal Chemistry in Eastern England, 2018, Hatfield UK

Introducing chemical diversity into a drug candidate late in the optimisation process has several applications including exploration of SAR (structure-activity relationships). Biocatalysis can provide access to chemical space in a complementary manner to chemical synthesis, thereby broadening coverage of the SAR map to better understand how small changes in the molecular structure affect biological potency.

In this late-stage functionalization project undertaken by Hypha and AstraZeneca, biotransformation of a small quantity of a drug lead was explored using a subset of microbes from Hypha’s oxidative strain panel, resulting in the identification of eight active oxidised derivatives. Sufficient purified material was generated for structure elucidation by 2D NMR and subsequent pIC50 determination via application of qNMR.