Diversity-oriented routes to thiopeptide antibiotics: total synthesis and biological evaluation of micrococcin P2

Org Biomol Chem. 2022 Mar 2;20(9):1893-1899. doi: 10.1039/d1ob02145a.

Abstract

We report the first total synthesis of micrococcin P2 (MP2, 1) by a diversity-oriented route that incorporates a number of refinements relative to earlier syntheses. Biological data regarding the activity of 1 against a range of human pathogens are also provided. Furthermore, we disclose a chemical property of MP2 that greatly facilitates medicinal chemistry work in the micrococcin area and describe a method to obtain MP2 by fermentation in B. subtilis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Bacteriocins / chemistry
  • Bacteriocins / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis* / drug effects
  • Peptides, Cyclic* / chemical synthesis
  • Peptides, Cyclic* / chemistry
  • Peptides, Cyclic* / pharmacology
  • Stereoisomerism
  • Sulfhydryl Compounds* / chemical synthesis
  • Sulfhydryl Compounds* / chemistry
  • Sulfhydryl Compounds* / pharmacology

Substances

  • Anti-Bacterial Agents
  • Bacteriocins
  • micrococcin
  • Sulfhydryl Compounds
  • micrococcin P2
  • Peptides, Cyclic