Chemical Investigations of Gymnastatin and Dankastatin Alkaloid Biosynthesis

Electrophilic natural products have provided fertile ground for understanding how nature inhibits protein function using covalent bond formation. The fungal strain Gymnascella dankaliensis has provided an especially interesting natural library of halogenated cytotoxic agents derived from tyrosine which feature an array of reactive functional groups. Herein we explore biosynthetic relationships between architecturally complex gymnastatin and dankastatin members, finding factors that favor formation of a given scaffold from a common intermediate. Additionally, we find that multiple natural products can be formed from aranorosin, a non-halogenated natural product also produced by gymnascella sp. fungi, using simple chloride salts. Finally, growth inhibitory activity of multiple members against challenging human triple negative breast cancer cells is reported.