In the drug discovery process, modification of the physicochemical properties of a molecule is often employed through functional group manipulation. The installation of desirable chemical motifs onto complex molecules usually requires divergent synthetic routes with multiple functional group interconversions. However, the emergence of new strategies for late-stage C-H functionalization, allows for the rapid construction of libraries from a single lead compound, preventing the parallel construction of each analog through multi-step syntheses. Recently, a class of natural products, the phyllanthusmins, have been shown to have cytotoxic activity against certain colon cancer cell lines. To further explore the structure-activity relationships of this class of natural products, several analogs have been studied. To streamline the synthesis of this library, we have utilized C-H functionalization methods developed in our lab for the post-synthetic modification of 2'-acetyl phyllanthusmin D to improve the potency of this natural product. Through these transformations we have shown that our methods are amenable to post-synthetic modification of complex systems.<br/>

Post-synthetic modification of drug candidates via C-H functionalization

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.