Total Synthesis of a Peptide Diatom Sex Pheromone Bearing a Sulfated Aspartic Acid

The peptide sex-inducing pheromone SIP⁺ (1) bearing an unusual sulfated aspartic acid residue induces sexual reproduction in diatom populations. Herein, we report the first total synthesis of SIP⁺ using both a sulfated building block approach and a solid-phase peptide synthesis (SPPS)-compatible late-stage sulfation strategy to assemble the natural product. The modular approaches provide concise routes to useful quantities of the natural product for future structure activity relationship studies examining the role of SIP⁺ in diatom biology.