Source: Dissertation Abstracts International, Volume: 71-07, Section: B, page: 4255.

Adviser: John L. Wood.

The search for natural products with biological activity related to cardiovascular disorders resulted in the isolation and structure elucidation of the indole alkaloid actinophyllic acid in 2005 Following isolation from the leaves of Alstonia actinophylla it was found to inhibit carboxypeptidase U (CPU) with an IC50 of 0.84 microM using a CPU/hippuricase coupled enzyme assay.

Efforts toward the total synthesis of actinophyllic acid are described, which includes two strategies. The first relied upon a sequential Michael addition/alkylation sequence to install the polycyclic carbon framework found in the natural product. The second strategy relied upon a more convergent route to the polycyclic core of actinophyllic acid. Both routes accessed intermediates possessing all carbon atoms requisite for the natural product. Highlights from these routes include a net amine conjugate addition through the intermediacy of a phosphonium salt and formation of a quaternary carbon by trapping a putative aza-isobenzofulvene intermediate with an enamine nucleophile, respectively.