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

doi:10.1021/ml3001775

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

Chemistry

Research output: Contribution to journal › Article

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 language	English (US)
Pages (from-to)	818-822
Number of pages	5
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	10
DOIs	https://doi.org/10.1021/ml3001775
State	Published - Oct 11 2012

Keywords

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

ASJC Scopus subject areas

Organic Chemistry
Drug Discovery
Biochemistry

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10.1021/ml3001775

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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.",

keywords = "antimicrobial activity, FtsZ, small molecule inhibitors, structure-activity relationships and optimization, totarol",

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AU - Kim, Michelle B.

AU - O'Brien, Terrence E.

AU - Moore, Jared T.

AU - Anderson, David E.

AU - Foss, Marie H.

AU - Weibel, Douglas B.

AU - Ames, James B.

AU - Shaw, Jared T.

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