Total synthesis of himastatin

Science. 2022 Feb 25;375(6583):894-899. doi: 10.1126/science.abm6509. Epub 2022 Feb 24.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacillus subtilis / drug effects
  • Bacillus subtilis / ultrastructure
  • Cell Membrane / drug effects
  • Cell Membrane / ultrastructure
  • Chemistry Techniques, Synthetic*
  • Dimerization
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Stereoisomerism

Substances

  • Anti-Bacterial Agents
  • Peptides, Cyclic
  • himastatin