The first semi-synthesis of (-)-melodinine K was completed from the monoterpene indole alkaloid (-)-tabersonine through regioselective enzymatic hydroxylation and Polonovski-Potier coupling. Regioselective borylation strategies were used to achieve meta-oxygenated derivatives of (-)-tabersonine for analysis in a Drosophila fruit fly Alzheimer’s phenotype model. A library of oxygenated and epoxidized bis-indole alkaloid analogs in the taberyunine class were prepared to conduct a structure activity relationship (SAR) study of the bis-indole framework against colon cancer and melanoma cell lines. Alkaloid aryl trifluoroborates were synthesized to increase nucleophilicity of arenes for unfavored alpha-arylations of tertiary amines on route to melosuavine bis-indole alkaloids. Overall, nine new bis-indole alkaloids were synthesized in the melodinine, taberyunine, and melosuavine class that showed strong cytotoxicity against a variety of melanoma, colon cancer, and renal cancer cell lines. / Chemistry