Studies show that currently, there are many drug candidates that have flat, aromatic structures with a high proportion of sp<sup>2</sup> carbons. However, in fact, drug candidates with more chiral centers and sp<sup>3</sup> carbons are more successful in clinical trials. This is because molecules with more quaternary carbons have higher selectivity and prevent undesirable interactions with other biomolecules. They are also believed to be more soluble and therefore better able to distribute themselves around the human body after administration. This research focuses on the synthesis of phenanthidinone analogs. Phenanthidinone has a flat, aromatic structure like other drug candidates which can cause unwanted bioactivities in the body. To make phenanthidinone analogs with quaternary carbon, a new enantioselective synthetic tool called the Birch-Heck sequence is used. The sequence includes 1) Birch reduction-alkylation, 2) amid synthesis, 3) MOM protection, and finally 4) Mizoroki-Heck reaction. A previous report from the Malachowski group described the process conducted with Pd catalyst, but the current project focused on the use of cheaper, more abundant nickel catalysts in the key Mizorori-Heck reaction. In this project, the substrate scope was expanded, and the enantioselectivity of phenanthridinone analogs was checked by chiral HPLC.

Enantioselective synthesis of phenanthidinone derivatives with quaternary carbon through the Birch-Heck sequence

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