Cancer has become a prominent health crisis with millions of new cases diagnosed each year. In response, researchers have often turned to nature with the goal of discovering molecules, often structurally sophisticated, which can serve as viable therapeutics. The success of naturally occurring treatments has been evidenced by the widespread use of anti-cancer agents, such as paclitaxel (1). Paclitaxel belongs to the taxoid family of natural products, which are highly oxygenated diterpenoids isolated from Yew trees. While paclitaxel has proven its utility as a chemotherapeutic, emerging cases of cancer resistance have made it highly desirable to study other structurally diverse taxoids that may be used as alternative treatments. Herein we present recent progress toward the enantiospecific total synthesis of oxo-bridged taxoids, such as taxagifine (2) and taxagifine III (3), from (S)-carvone (4). Key features of this work include constructing the carbon skeleton (5) through a highly efficient Pd-catalyzed C–C bond cleavage/cross-coupling of two carvone-derived fragments followed by an intramolecular aldol cyclization to forge the central 8-membered ring. Additionally, we showcase the power of strategic oxidation tactics in elaborating this core to the fully oxygenated taxagifine skeleton (6).

Application of a C–C cleavage strategy for the total synthesis of taxoid natural products

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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