With the current decline in new drug approvals, untapped biological resources such as natural products may provide an opportunity for the discovery of new pharmaceutical agents1 . This poster describes a novel approach towards the total synthesis of four structurally related peptide-based natural products 1-4. Polydiscamide B-D2 (1-3) possess agonist activity (EC50 = 1.26, 3.57 and 2.80 mM, respectively) against the human sensory neuron-specific G-protein coupled receptor (SNSR) while Microspinosamide3 (4) possesses potent anti-HIV activity (EC50 = 100 nM). Assembly of these natural products via an unprecedented native chemical ligation (NCL)-oxidation approach will be described.
