Taxoid natural products are molecules whose structural complexity has challenged the synthetic chemistry community for decades. In particular, taxol has inspired the efforts of synthetic chemists, partly for the aforementioned creative challenge, but also due to its utility as a chemotherapeutic agent to treat lung, ovarian, and breast cancers. However, the current total syntheses of taxol involve at least 40 steps; as a result, total synthesis has not proved a viable strategy for providing sufficient quantities of taxol for clinical treatment. In addition, treatment opportunities with taxol are often hampered by either innate or developed resistance in the patient.<br/><br/>Taxagifine is a taxoid natural product whose structural features differ with those of taxol in at least two major ways: taxagifine lacks the characteristic oxetane D ring of taxol, and it contains an extra tetrahydrofuran ring bridging the A ring. These structural differences suggest that taxagifine may exhibit chemotherapeutic activity analogous to that of taxol, but potentially without the same pathways leading to resistance. We decided to embark on a total synthesis of taxagifine to investigate this possibility. Through a C–C activation/cross-coupling/aldol sequence stitching together A- and C-ring precursors derived from (S)-carvone, we have been able to rapidly construct the core ABC ring structure of taxagifine, with much of the ultimately desired oxygenation already in place.

Utilizing a C–C activation/cross-coupling strategy toward the total synthesis of taxagifine

253rd National Meeting (2017)

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