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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

Thermodynamic properties
Derivatives
Diterpenes
Biological Products
Ketones
Cell Division
Nitrogen
Carbon
Cells
Atoms
Proteins
Experiments
indole
totarol

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., ... 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

The synthesis and antimicrobial activity of heterocyclic derivatives of totarol. / Kim, Michelle B.; O'Brien, Terrence E.; Moore, Jared T.; Anderson, David E.; Foss, Marie H.; Weibel, Douglas B.; Ames, James B.; Shaw, Jared T.

In: ACS Medicinal Chemistry Letters, Vol. 3, No. 10, 11.10.2012, p. 818-822.

Research output: Contribution to journalArticle

Kim, MB, O'Brien, TE, Moore, JT, Anderson, DE, Foss, MH, Weibel, DB, Ames, JB & Shaw, JT 2012, 'The synthesis and antimicrobial activity of heterocyclic derivatives of totarol', ACS Medicinal Chemistry Letters, vol. 3, no. 10, pp. 818-822. https://doi.org/10.1021/ml3001775
Kim MB, O'Brien TE, Moore JT, Anderson DE, Foss MH, Weibel DB et al. The synthesis and antimicrobial activity of heterocyclic derivatives of totarol. ACS Medicinal Chemistry Letters. 2012 Oct 11;3(10):818-822. https://doi.org/10.1021/ml3001775
Kim, Michelle B. ; O'Brien, Terrence E. ; Moore, Jared T. ; Anderson, David E. ; Foss, Marie H. ; Weibel, Douglas B. ; Ames, James B. ; Shaw, Jared T. / The synthesis and antimicrobial activity of heterocyclic derivatives of totarol. In: ACS Medicinal Chemistry Letters. 2012 ; Vol. 3, No. 10. pp. 818-822.
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