Total synthesis of himastatin

• DOI: 10.1126/science.abm6509
• Publication Date: 2022-02-24T18:56:26Z
• Authors: Kyan A. D’Angelo; Carly K. Schissel; Bradley L. Pentelute; Mohammad Movassaghi
• Keywords: Cyclic; Molecular Structure; General Science & Technology; Organic Chemistry; Synthetic; Cell Membrane; Stereoisomerism; Chemistry Techniques; Chemistry Techniques, Synthetic; Peptides, Cyclic; 01 natural sciences; Anti-Bacterial Agents; 3. Good health; 0104 chemical sciences; Chemical Sciences; Peptides; Dimerization; Bacillus subtilis

The natural product himastatin has an unusual homodimeric structure that presents a substantial synthetic challenge. We report the concise total synthesis of himastatin from readily accessible precursors, incorporating a final-stage dimerization strategy that was inspired by a detailed consideration of the compound’s biogenesis. Combining this approach with a modular synthesis enabled expedient access to more than a dozen designed derivatives of himastatin, including synthetic probes that provide insight into its antibiotic activity.