Discovery of potent parthenolide-based antileukemic agents enabled by late-stage P450-mediated C-H functionalization.

ABSTRACT: The sesquiterpene lactone parthenolide has recently attracted considerable attention owing to its promising antitumor properties, in particular in the context of stem-cell cancers including leukemia. Yet, the lack of viable synthetic routes for re-elaborating this complex natural product has represented a fundamental obstacle toward further optimization of its pharmacological properties. Here, we demonstrate how this challenge could be addressed via selective, late-stage sp(3) C-H bond functionalization mediated by P450 catalysts with tailored site-selectivity. Taking advantage of our recently introduced tools for high-throughput P450 fingerprinting and fingerprint-driven P450 reactivity prediction, we evolved P450 variants useful for carrying out the highly regioselective hydroxylation of

SUBMITTER: Kolev JN 

PROVIDER: S-EPMC3904131 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature