Concise synthesis of spergualin-inspired molecules with broad-spectrum antibiotic activity

Victoria A. Assimon, Hao Shao, Sylvie Garneau-Tsodikova, Jason E. Gestwicki

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


There is a growing need to identify new, broad-spectrum antibiotics. The natural product spergualin was previously shown to have promising anti-bacterial activity and a privileged structure, but its challenging synthesis had limited further exploration. For example, syntheses of spergualin and its analogs have been reported in approximately 10 linear steps, with overall yields between 0.3 and 18%. Using the Ugi multi-component reaction, we assembled spergualin-inspired molecules in a single step, dramatically improving the overall yield (20% to 96%). Using this strategy, we generated 43 new analogs and tested them for anti-bacterial activity against two Gram-negative and four Gram-positive strains. We found that the most potent analogue, compound 6, had MIC values between 4 and 32 μg mL-1 against the six strains, which is a significant improvement on spergualin (MIC ~ 6.25 to 50 μg mL-1). These studies provide a concise route to a broad-spectrum antibiotic with a novel chemical scaffold.

Original languageEnglish
Pages (from-to)912-918
Number of pages7
Issue number5
StatePublished - May 1 2015

Bibliographical note

Publisher Copyright:
© The Royal Society of Chemistry 2015.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


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