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 | |
| State | Published - 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
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 journal › Article
}
TY - JOUR
T1 - The synthesis and antimicrobial activity of heterocyclic derivatives of totarol
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.
PY - 2012/10/11
Y1 - 2012/10/11
N2 - 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.
AB - 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.
KW - antimicrobial activity
KW - FtsZ
KW - small molecule inhibitors
KW - structure-activity relationships and optimization
KW - totarol
UR - http://www.scopus.com/inward/record.url?scp=84867342820&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867342820&partnerID=8YFLogxK
U2 - 10.1021/ml3001775
DO - 10.1021/ml3001775
M3 - Article
VL - 3
SP - 818
EP - 822
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
SN - 1948-5875
IS - 10
ER -