The synthesis and antimicrobial activity of heterocyclic derivatives of totarol

Michelle B. Kim, Terrence E. O'Brien, Jared T. Moore, David E. Anderson, Marie H. Foss, Douglas B. Weibel, James B. Ames, Jared T. Shaw

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12 Scopus citations

Abstract

The synthesis and antimicrobial activity of heterocyclic analogues of the diterpenoid totarol are described. An advanced synthetic intermediate with a ketone on the A-ring is used to attach fused heterocycles, and a carbon-to-nitrogen atom replacement is made on the B-ring by de novo synthesis. A-ring analogues with an indole attached exhibit, for the first time, enhanced antimicrobial activity relative to the parent natural product. Preliminary experiments demonstrate that the indole analogues do not target the bacterial cell division protein FtsZ as had been hypothesized for totarol.

Original languageEnglish (US)
Pages (from-to)818-822
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume3
Issue number10
DOIs
StatePublished - Oct 11 2012

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Keywords

  • antimicrobial activity
  • FtsZ
  • small molecule inhibitors
  • structure-activity relationships and optimization
  • totarol

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Kim, M. B., O'Brien, T. E., Moore, J. T., Anderson, D. E., Foss, M. H., Weibel, D. B., Ames, J. B., & Shaw, J. T. (2012). The synthesis and antimicrobial activity of heterocyclic derivatives of totarol. ACS Medicinal Chemistry Letters, 3(10), 818-822. https://doi.org/10.1021/ml3001775