C-H modification of natural products: a minimalist enabling tactic for drug discovery, API processing and bioconjugation.

Intrusion into the C-H chemical space of natural products through the strategic deployment of C-H functionalization reactions could lead to incredibly new molecular diversities with an unforeseen impact on biological functions. Based on this hypothesis, semisynthetic C-H modification of natural products is emerging as a minimalist tactic in natural product based drug discovery. Several examples of C-H modification of natural products, resulting in functional gains in key pharmacological attributes viz. potency, aqueous solubility and DMPK profile, along with opportunities in allied areas such as API processing, bioconjugation, and target deconvolution, continue to surface in the recent literature. The strategy has already recorded commercial success in the development of antineoplastic drugs topotecan and irinotecan and in industrial production of pravastatin, calcitriol and artemisinin. This Feature Article highlights the broad contours of this evolving paradigm at the interface of natural product and synthetic chemistry research to accelerate and widen the scope of natural product-based drug discovery.