The Malachowski group has previously focused on synthesizing phenanthridinone analogs with more chiral centers and sp<sup>3</sup> carbons, developing the Birch-Heck reaction sequence as an efficient tool to generate these molecules. Another class of molecules known as cephalotaxus diterpenoids have reported antitumor, antineoplastic, and antiviral bioactivities. The sequence used for generating enantioselective phenanthridinone-like molecules can be applied to the synthesis of cephalotaxus diterpenoids. Using the Birch-Heck sequence previously studied in the Malachowski lab group, this research focused on synthesizing a tricyclic core structure via an enantioselective Heck reaction. Starting with ethyl benzoate, different Birch reduction alkylating reactions were performed using a variety of alkylating agents. This was followed by a nickel (II) catalyzed Mizoroki-Heck reaction that created a 6-6-6 tricyclic ring structure. These tricyclic cores can then serve as the basis for total synthesis sequences to get to the full cephalotaxus diterpenoid structure, for example cephanolide B, C, D and G. The Birch-Heck sequence is important because, relative to prior reports, it could more efficiently and enantioselectively generate an advanced intermediate for bioactive cephalotaxus diterpenoids, which could be useful in drug development efforts with this family of bioactive natural products.

Synthesis of tricyclic core structures for cephalotaxus diterpenoids via the enantioselective Birch-Heck Sequence

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